Congestive Heart Failure - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

CONGESTIVE HEART FAILURE A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FEREN...

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

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

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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright 2003 by ICON Group International, Inc. Copyright 2003 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., 1960Congestive Heart 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: 0-597-83838-0 1. Congestive 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.

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

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Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on congestive 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 CONGESTIVE HEART FAILURE .................................................................. 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Congestive Heart Failure .............................................................. 5 E-Journals: PubMed Central ....................................................................................................... 65 The National Library of Medicine: PubMed ................................................................................ 66 CHAPTER 2. NUTRITION AND CONGESTIVE HEART FAILURE ...................................................... 113 Overview.................................................................................................................................... 113 Finding Nutrition Studies on Congestive Heart Failure........................................................... 113 Federal Resources on Nutrition ................................................................................................. 118 Additional Web Resources ......................................................................................................... 118 CHAPTER 3. ALTERNATIVE MEDICINE AND CONGESTIVE HEART FAILURE ................................ 121 Overview.................................................................................................................................... 121 National Center for Complementary and Alternative Medicine................................................ 121 Additional Web Resources ......................................................................................................... 128 General References ..................................................................................................................... 133 CHAPTER 4. DISSERTATIONS ON CONGESTIVE HEART FAILURE.................................................. 135 Overview.................................................................................................................................... 135 Dissertations on Congestive Heart Failure................................................................................ 135 Keeping Current ........................................................................................................................ 137 CHAPTER 5. CLINICAL TRIALS AND CONGESTIVE HEART FAILURE ............................................ 139 Overview.................................................................................................................................... 139 Recent Trials on Congestive Heart Failure................................................................................ 139 Keeping Current on Clinical Trials ........................................................................................... 148 CHAPTER 6. PATENTS ON CONGESTIVE HEART FAILURE ............................................................ 151 Overview.................................................................................................................................... 151 Patents on Congestive Heart Failure ......................................................................................... 151 Patent Applications on Congestive Heart Failure ..................................................................... 176 Keeping Current ........................................................................................................................ 205 CHAPTER 7. BOOKS ON CONGESTIVE HEART FAILURE ................................................................ 207 Overview.................................................................................................................................... 207 Book Summaries: Federal Agencies............................................................................................ 207 Book Summaries: Online Booksellers......................................................................................... 212 The National Library of Medicine Book Index ........................................................................... 214 Chapters on Congestive Heart Failure....................................................................................... 215 CHAPTER 8. MULTIMEDIA ON CONGESTIVE HEART FAILURE ..................................................... 217 Overview.................................................................................................................................... 217 Video Recordings ....................................................................................................................... 217 Bibliography: Multimedia on Congestive Heart Failure............................................................ 218 CHAPTER 9. PERIODICALS AND NEWS ON CONGESTIVE HEART FAILURE .................................. 221 Overview.................................................................................................................................... 221 News Services and Press Releases.............................................................................................. 221 Newsletter Articles .................................................................................................................... 223 Academic Periodicals covering Congestive Heart Failure ......................................................... 224 CHAPTER 10. RESEARCHING MEDICATIONS................................................................................. 225 Overview.................................................................................................................................... 225 U.S. Pharmacopeia..................................................................................................................... 225 Commercial Databases ............................................................................................................... 227 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 231 Overview.................................................................................................................................... 231

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NIH Guidelines.......................................................................................................................... 231 NIH Databases........................................................................................................................... 233 Other Commercial Databases..................................................................................................... 235 APPENDIX B. PATIENT RESOURCES ............................................................................................... 237 Overview.................................................................................................................................... 237 Patient Guideline Sources.......................................................................................................... 237 Finding Associations.................................................................................................................. 245 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 247 Overview.................................................................................................................................... 247 Preparation................................................................................................................................. 247 Finding a Local Medical Library................................................................................................ 247 Medical Libraries in the U.S. and Canada ................................................................................. 247 ONLINE GLOSSARIES................................................................................................................ 253 Online Dictionary Directories ................................................................................................... 256 CONGESTIVE HEART FAILURE DICTIONARY .................................................................. 257 INDEX .............................................................................................................................................. 341

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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 congestive 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 congestive 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 congestive 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 congestive 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 congestive 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 congestive 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 CONGESTIVE HEART FAILURE Overview In this chapter, we will show you how to locate peer-reviewed references and studies on congestive 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 congestive 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 “congestive 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

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management, and nursing interventions in patients with ESRD. One table summarizes 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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Congestive Heart Failure in Type 2 Diabetes: Prevalence, Incidence, and Risk Factors Source: Diabetes Care. 24(9): 1614-1619. September 2001. 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

Studies

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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).

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

Project Title: A ENHANCEMENT

RANDOMIZED

TRIAL

OF

HOME

SELF-EFFICACY

Principal Investigator & Institution: Jerant, Anthony F.; Family and Community Medicine; University of California Davis Sponsored Programs, 118 Everson Hall Davis, Ca 95616 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 31-DEC-2007 Summary: (provided by applicant): Background: Key reasons for the "quality chasm" between current and ideal chronic illness care are that our health care system is insensitive to patient preferences, provider-driven, and disease-focused. By contrast, a common goal among proposed patient-centered care models is to foster continuous healing relationships between patients and the health care system. Such relationships allow patients to receive care over time via a variety of communication media, rather than just via episodic office visits. Home health care can foster such relationships and improve outcomes for patients with a variety of conditions. Home interventions may be particularly useful in caring for the growing number of people with chronic illnesses and accompanying functional limitations that might limit their access to communitybased interventions. However, trials comparing the effectiveness and cost-effectiveness of the wide array of home care models are limited, and the mechanisms that underlie their effectiveness remain unclear. Aims/Hypotheses: This study will address these research gaps. The study hypotheses are: a) Each of three home interventions will result in improvements in patient self-efficacy, adherence to care, and health-related quality of life (HRQOL) compared with usual care but will not differ statistically; b) From the 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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payer's perspective, all the interventions will be cost saving compared with usual care, and a standard telephone intervention will be the most cost saving; and c) Self-efficacy will improve temporally before adherence to care and HRQOL. Methods: This will be a randomized controlled study of four groups, comparing the effectiveness and incremental cost-effectiveness of three different home-based care models and usual care in improving chronic illness outcomes. The chronic illnesses targeted will be arthritis, asthma, chronic obstructive pulmonary disease, congestive heart failure, depression, and diabetes mellitus. Trained laypersons will deliver the interventions, a self efficacy enhancement program (vs. usual care). The home care delivery media in the models will be in person visits, videophone calls, and standard telephone calls. The primary outcomes will be HRQOL and costs. Implications: Better understanding of the mechanisms of effectiveness of home care will facilitate the development of optimal home interventions. The findings will help policymakers, payers, and providers identify which interventions to implement. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ACTION - A CHF TRIAL INVESTIGATING OUTCOMES OF EXERCISE Principal Investigator & Institution: Bittner, Vera A.; Professor of Medicine; Medicine; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-JUL-2006 Summary: (provided by applicant): The primary aim of the ACTION Trial is to determine the long-term safety and effectiveness of exercise training for New York Heart Association Classes II-IV congestive heart failure patients in addition to standard of care versus a strategy of standard care alone. The secondary objective is to determine the incidence and significance of exercise-related complications, the effect on exercise tolerance and quality of life, and the cost-effectiveness of training. The exercise training will include 36 facility-based training sessions followed by home-based exercise and interval facility sessions. Training will be at 60-70% of heart rate reserve. Patients randomized to the training arm will train by either walking or bicycle ergometers. Treadmills or exercise bicycles will be provided to training patients by the coordinating center, if desired. Effectiveness will be defined as the primary combined endpoint of allcause mortality and all-cause hospitalizations. The expected annual baseline rate is 30% for the control group. The expected non-adherence and drop-out rate is 35% the first year and 15% annually thereafter, with a cross-over rate of 5% per year. The regional center team and the coordinating center will implement multiple strategies to improve adherence in patients in the training arm. Using these assumptions, a total sample size of 3000 subjects will be required to detect a 20% reduction in the primary outcome with an alpha level of 0.05 and a power greater than 80%. If the non-adherence and drop-out rate decrease to 30% in the first year and 12.5% annually thereafter, the power to detect a 20% difference is greater than 90%. The primary analysis will be based on intent-to-treat. The trial will take place over 5 years with an initial 6 months for planning, training, and implementation; 3 years of enrollment; 1 year of follow-up; and 6 months for close out, analysis, and presentation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ACTION EQOL STUDY Principal Investigator & Institution: Schulman, Kevin A.; Director, Center for Clinical and Geneti; Medicine; Duke University Durham, Nc 27706

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7

Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-JUL-2007 Summary: (provided by applicant): The primary aim of the ACTION Trial is to determine the long-term safety and effectiveness of exercise training for New York Heart Association Classes II-IV congestive heart failure patients in addition to standard of care versus a strategy of standard care alone. The secondary objective is to determine the incidence and significance of exercise-related complications, the effect on exercise tolerance and quality of life, and the cost-effectiveness of training. The exercise training will include 36 facility-based training sessions followed by home-based exercise and interval facility sessions. Training will be at 60-70% of heart rate reserve. Patients randomized to the training arm will train by either walking or bicycle ergometers. Treadmills or exercise bicycles will be provided to training patients by the coordinating center, if desired. Effectiveness will be defined as the primary combined endpoint of allcause mortality and all-cause hospitalizations. The expected annual baseline rate is 30% for the control group. The expected non-adherence and drop-out rate is 35% the first year and 15% annually thereafter, with a cross-over rate of 5% per year. The regional center team and the coordinating center will implement multiple strategies to improve adherence in patients in the training arm. Using these assumptions, a total sample size of 3000 subjects will be required to detect a 20% reduction in the primary outcome with an alpha level of 0.05 and a power greater than 80%. If the non-adherence and drop-out rate decrease to 30% in the first year and 12.5% annually thereafter, the power to detect a 20% difference is greater than 90%. The primary analysis will be based on intent-to-treat. The trial will take place over 5 years with an initial 6 months for planning, training, and implementation; 3 years of enrollment; 1 year of follow-up; and 6 months for close out, analysis, and presentation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

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

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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 •

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 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

Studies

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Project Title: ALPHA MYOSIN-INDUCING COMPOUNDS AND CONTRACTILITY Principal Investigator & Institution: Schreiber, Kathy L.; 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): Chronic heart failure (CHF) is a diverse group of cardiovascular diseases that affects millions of Americans, with approximately 550,000 new cases diagnosed each year. The annual estimated health care cost is $10-40 billion, and it is predicted that the incidence of CHF will increase over the next decade. Patients diagnosed with CHF have a persistently poor prognosis, emphasizing the need for additional novel treatment approaches. The initial compensatory response in the disease process is thought to improve cardiac function, but the heart undergoes decompensation and cardiac function deteriorates if the hypertrophy is sustained. Eventually, CHF culminates in the clinical symptom of cardiac pump dysfunction. The relative abundance of isoforms of certain contractile proteins are altered during the disease process and contribute to the contractile defects. Myosin is the most abundant protein found in the contractile apparatus, and is responsible for mediating contraction through its interaction with actin. Two myosin isoforms are found in the heart (alpha and beta),and the relative proportion of these isoforms is dramatically affected in animal models of hypertrophy and in patients with end-stage CHF. Therefore, a novel approach to treat CHF patients is to restore myosin isoform expression to those resembling healthy individuals. Myogen, Inc. seeks to identify lead compounds that increase protein levels of a myosin heavy chain, a contractile protein that is severely downregulated in heart failure. These therapeutic agents can be used to improve cardiac contractile performance and induce reverse remodeling in CHF patients. In this Phase I proposal, some novel compounds recently discovered at Myogen will be tested to assess their effect on contractility in vitro. In a future Phase II proposal, additional compounds will be identified using a high throughput screening assay developed at Myogen, and compounds that improve contractility in vitro will be studied in rat models of cardiac hypertrophy. Phase III will focus on optimizing compounds through the use of medicinal chemistry until a lead compound is identified with the desired characteristics suitable for advancement to clinical studies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ANGIOTENSIN, LEPTIN, AND THE SYMPATHETIC NERVOUS SYSTEM Principal Investigator & Institution: Cassis, Lisa A.; Professor; Pharmacol & Exper Therapeutics; University of Kentucky 109 Kinkead Hall Lexington, Ky 40506 Timing: Fiscal Year 2001; Project Start 14-AUG-1998; Project End 31-JUL-2003 Summary: (Adapted from the application): Angiotensin II (Ang II), a peptide integral to the central control of blood pressure, regulates sympathetic neurotransmission. The pathophysiological relevance of Ang II/sympathetic interactions has been examined in hypertension and congestive heart failure; however, the relevance of this interaction at noncardiovascular organs innervated by the sympathetic nervous system has not been examined. Preliminary studies demonstrate that chronic infusion of Ang II to rats resulted in a dose-dependent elimination of weight gain and reduction in body weight through pressor-independent mechanisms. The working hypothesis of the proposed studies is that Ang II regulates body weight by activating the sympathetic nervous system, lipids, reducing food intake and altering secretion of adipose-derived leptin. All of the proposed studies will be performed in a rat model of chronic Ang II infusion. The

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Congestive Heart Failure

first hypothesis is that Ang II regulates energy expenditure by activating the sympathetic nervous system. Several different approaches will be used to determine the role of the sympathetic nervous system in the effect of Ang II. First the time course for alterations in norepinephrine (NE) turnover and kinetic parameters of the ligand biding site of the NE transporter will be determined in white and brown adipose tissue. Examination of the time course form alterations in release of NE from slices of white and brown adipose tissue and the in vitro effect of Ang II to increase evoked NE release will be examined. The effect of beta blockade on Ang II-regulation of body weight will be examined. To determine if Ang II increases energy expenditure by altering secretion of leptin protein, the time course for alterations in plasma leptin will be determined. Administration of Ang II to ob/ob mice lacking functional leptin will be examined to determine the role of leptin in Ang II-regulation of body weight. The effect of Ang II to mobilize lipids from brown and white adipose tissue will be determined. The role of AT1 receptor in Ang II-disposition of adipose tissue in response to Ang II infusion will be examined. In Hypothesis 2, the role of alterations in food intake in the weightreducing effects of Ang II will be determined. The physiologic/ pathophysiologic significance of Ang II-regulation of body weight is related to disease states whereby plasma Ang II concentrations are elevated (congestive heart failure) or decreased (obesity), contributing to the dysregulation of body weight. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: AQUAPORIN-2 EXCRETION IN DISORDERS OF WATER BALANCE Principal Investigator & Institution: Cadnapaphornchai, Melissa A.; Pediatrics; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 31-JUL-2005 Summary: (adapted from the application) Normal water metabolism is essential to body fluid homeostasis. The major determinants of normal water balance include arginine vasopressin (AVP), renal function, and thirst. Recent investigations have described the cloning and characterization of the water channel aquaporin-2 (AQP-2), which is located in the principal cell of the kidney collecting duct. Under the influence of AVP, AQP-2 inserts into the apical membrane, allowing reabsorption of water to occur. Studies in animals and humans suggest that alterations in the regulation and expression of AQP-2 in certain physiologic and pathologic states may contribute to such complications as hyponatremia, hypoosmolality, and edema. During exocytic shuttling of AQP-2 to the apical collecting duct membrane, a small percentage of AQP-2 is lost in the urine. Measurement of this urinary AQP-2 protein can be reliably performed by radioimmunoassay; this test represents a novel tool for evaluation of AVP action in the collecting duct of the human kidney in health and disease. In these studies, we will examine urinary AQP-2 excretion in patients during pregnancy and the menstrual cycle, and in patients with congestive heart failure, cirrhosis, nephrotic syndrome, and acquired nephrogenic diabetes insipidus due to lithium therapy or autosomal dominant polycystic kidney disease. An interpretation of the relationship between urinary AQP-2, serum and urine osmolality, and plasma AVP will provide insight into the control of body fluid homeostasis. The role of the vasopressin V2 receptor antagonist, CIPC-41061, in the treatment of volume overload, edema, and hyponatremia will be explored. A comprehensive understanding of AQP-2 regulation in humans will lead to unique and more direct interventions in the therapy of disordered water metabolism. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: BBA EFFECTS ON GEOGRAPHIC VARIATION IN POST-ACUTE CARE Principal Investigator & Institution: Lin, Wen-Chieh; Family and Community Medicine; University of Missouri Columbia 310 Jesse Hall Columbia, Mo 65211 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2004 Summary: (Provided by Applicant): In response to the rapid growth in payments for post-acute care (PAC) services, Congress enacted Medicare reforms as part of the Balanced Budget Act of 1997 (BBA) for each PAC service. The reforms mandated a series of separate case-mix adjusted prospective payment systems, each with its own implementation timeline. In addition to the overall effects, the BBA's effects on PAC use varied substantially across geographic areas. For example, in the case of skilled nursing facility use from 1998 to 2000, the average change relative to 1996 for stroke patients was 2.7%.at the national level, but it ranged from -12% to 24% across regions (the nine United States Census Bureau divisions). This varied response raises concerns that the hospital discharge process may be driven by payment policy rather than by clinical needs and individual preferences. Furthermore, varied changes in PAC use across regions might lead to untoward consequences, such as early hospital readmission. As efforts continue to reform PAC services and payment systems, it is essential that policymakers understand how different payment mechanisms associate with geographic variation in PAC use. The proposed study seeks to: 1) analyze geographic variation in PAC use before and after the BBA changes; 2) explore whether utilization and cost have shifted among PAC settings and whether early hospital readmission has increased; and 3) investigate how the contributions of patient, hospital, and market area characteristics in explaining PAC use differ between pre- and post-BBA periods. We will analyze the Center for Medicare & Medicaid Services' 5% sample of Medicare claims data from 1996 to 2000 to study the initial effect of the BBA changes on geographic variation in PAC use. We will focus on six diseases associated with high PAC use: stroke, hip procedure, hip fracture, chronic obstructive pulmonary disease, pneumonia, and congestive heart failure. The selected diseases provide a contrast between rehabilitative and medical conditions. The stability, the degree, and the association of geographic variation in PAC use before and after the BBA changes will be examined. Shifts in utilization and costs will be presented as correlations between changes in PAC use, hospital length of stay, and early hospital readmission. Finally, we will estimate multinomial logit models to explore changes in contribution to explain PAC use by patient, hospital, and market area characteristics after the BBA changes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CARDIAC REGULATION

HYPERTROPHY

INDUCED

METABOLIC

GENE

Principal Investigator & Institution: Barger, Philip M.; 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

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Congestive Heart Failure

about the hypertrophy signaling pathway linked extracellular stimulus to transcriptional regulation. The broad goals of this proposal are to delineate the molecular regulatory signals which ultimately contribute to down-regulation of FAO during hypertrophy. This proposal is specifically designed to i) characterize alterations in fatty acid beta-oxidation gene transcription in cultured rat neonatal cardiocytes undergoing hypertrophy and to delineate the specific cis-acting elements mediating that response utilizing Northern and Western blot analysis, RNase protection, and transient gene transfer studies with FAO enzyme gene promoters; ii) identify the specific transcriptional regulators that bind to the responsive elements in the promoters of betaoxidation genes during cardiocyte hypertrophy utilizing electrophoretic mobility shift assay, cotransfection, Northern and Western blot analysis, RNase protection, and immunofluorescence; iii) determine whether the activity of the regulators are increased during hypertrophy by phosphorylation events utilizing in vitro and in vivo phosphorylation studies, inhibitors of known signal transduction cascades, and phosphorylation site mutations with emphasis on the mitogen-activated protein kinase pathway. The longterm goals will be to determine whether reactivation of this fetal metabolic gene program and/or downregulation of fatty acid beta-oxidation leads to a maladaptive hypertrophied phenotype and thus promotes the transition to heart failure. If so, the studies outlined above will have identified potential targets for therapeutic interventions aimed at delaying or even preventing progression to end-stage cardiomyopathy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CARDIOVASCULAR DISEASE IN RHEUMATOID ARTHRITIS Principal Investigator & Institution: Morgan, Mary C.; Assistant Professor; Medicine; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2001; Project Start 27-JUL-2001; Project End 31-MAY-2006 Summary: (Taken from the applicants abstract): Rheumatoid Arthritis (RA) is a chronic, inflammatory autoimmune disorder that affects 1% of the U.S. population, with women of childbearing age preferentially stricken. There is a significant reduction in life expectancy in women with RA, which is due in part to premature cardiovascular disease. Acute myocardial infarction (MI) and congestive heart failure (CHF) are the leading causes of death in RA. The etiology of cardiovascular disease in RA likely involves an interaction between inflammation-induced and immune-mediated vascular injury, traditional risk factors, and hormonal factors. In RA, synovial inflammation is characterized by CD4+ T cell activation and pro-inflammatory cytokine excess, both within the joint and in the systemic circulation. The influence of such chronic immune system stimulation on atherogenesis and cardiovascular clinical events such as MI and CHF is unknown. However, recent work has suggested that inflammation is responsible for atherosclerotic plaque disruption with vascular occlusion in non-RA patients. Increasing evidence implicates cellular and humoral components of the immune system in atherosclerotic plaque destabilization. Specifically, pro-inflammatory cytokines and CD4+ T cells have been identified in atherosclerotic lesions in association with plaque rupture and acute ischemic cardiac events, suggesting that they participate in plaque destabilization. This award will provide the opportunity for me, Mary Chester M. Wasko, MD, MSc, to obtain the specific skills necessary to develop into an independent clinical investigator. In this study I propose to: 1) determine the prevalence and predictors of vascular disease in women with RA; 2) compare the prevalence of vascular disease and associated risk factors in RA and systemic lupus erythematosus (SLE), an autoimmune disease also characterized by premature MI and CHF in young women;

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and 3) compare the prevalence of vascular disease in RA patients with and without a previous cardiovascular event. This study will provide valuable information for designing a future, prospective, multicenter study examining the value of B-mode ultrasound and EBCT in predicting incident cardiovascular events in patients with RA. 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 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

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Project Title: CAUSES OF SLEEP-INDUCED BREATHING INSTABILITIES Principal Investigator & Institution: Dempsey, Jerome A.; Professor; Preventive Medicine; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2001; Project Start 01-APR-1999; Project End 31-MAR-2003 Summary: During sleep and with the loss of the "wakefulness" drive to pump and upper airway respiratory muscles, the control of breathing becomes highly dependent upon and vulnerable to reflexive feedback inputs from chemoreceptors and

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Congestive Heart Failure

mechanoreceptors. Accordingly, sleep-induced breathing instabilities are common and have a significant prevalence even in the general population. Sleep unmasks a highly sensitive hypocapnic-induced apneic threshold, but we do not know what role this mechanism plays in various types of sleep-disordered breathing, because we do not know its sites of action, its changes in sensitivity in the presence of powerful background influences such as CNS hypoxia, chronic hypocapnia/hypercapnia, changing sleep states, or changing stimuli to breathe which might be specific to sleep. We will use sleeping humans and dogs, the latter with extra corporeal perfusion of isolated carotid chemoreceptors-to quantify the effect of these influences on both the apneic threshold and on the important stabilizing mechanism of short term potentiation of ventilatory output. This dog model with isolation of carotid chemoreceptors will also be used to address the question of central versus peripheral hypoxic effects on periodic breathing in sleep. A second dog model as well as human patients with chronic heart failure will be studied to address the mechanisms of Cheyne-Stokes respiration, with specific emphasis on the effects of the added stimulus to hyperventilation originating from the lungs of the patient in congestive heart failure. Finally, we will use dogs and humans-with and without innervated lungs-to address the role of non-chemical, mechanoreceptor inhibitory feedback effects during sleep on upper airway and pump muscles; a) influences from high frequency low amplitude pressure oscillations in the upper airway; b) the effects of amplitude, timing and duration of normocapnic mechanical ventilation on the resetting of inherent respiratory rhythm and on the "shortterm inhibition" of respiratory motor output following cessation of phasic inhibitory sensory input. These latter studies conduced in sleep are important to testing the sensitivity of respiratory control mechanisms to mechanical feedback-a problem which remains relatively unexplored, especially in the human. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TRAINING

CHF

TRIAL

INVESTIGATING

OUTCOMES

OF

EXERCISE

Principal Investigator & Institution: Kitzman, Dalane W.; Associate Professor; Internal Medicine; Wake Forest University Health Sciences Winston-Salem, Nc 27157 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-JUL-2006 Summary: (Applicant?s Abstract) The primary aim of ACTION is to determine the longterm safety and efficacy of exercise training for New York Heart Association Classes IIIV congestive heart failure patients in addition to standard of care versus a strategy of standard care alone. The secondary objective is to determine the incidence and significance of exercise-related complications. As part of this objective, the investigators will determine the specific characteristics of patients with increased benefit or increased risk from exercise. The exercise training will include 36 supervised training sessions followed by home exercise and interval supervised sessions. Training will be at 60-70% of peak VO2. Efficacy will be defined as the primary combined endpoint of all-cause mortality and all-cause hospitalizations. These clinical endpoints will be supported by physiological, resource utilization, and quality-of-life endpoints. The expected annual baseline rate is 30% for the control group. The expected dropout rate is 35% for the first year and 15%, with a cross-over rate of 5% per year. Using these assumptions, a total sample size of 3000 subjects will be required to detect a 20% reduction in the primary outcome with an alpha level of 0.05 and a power of 80%. The trial will take place over 5 years with an initial 6 months for finalizing the study and training the Regional Centers, 3 years of enrollment, 1 year of follow-up, and 6 months for close out, analysis and presentation.

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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CHRONIC ISCHEMIC LEFT VENTRICULAR DYSFUNCTION Principal Investigator & Institution: Kaul, Sanjiv; Professor of Cardiology; Internal Medicine; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904 Timing: Fiscal Year 2001; Project Start 01-SEP-2001; Project End 31-AUG-2005 Summary: Chronic coronary artery disease is now the major cause of congestive heart failure (CHF) in the western hemisphere. With more people living longer, the incidence of CHF is rapidly on the rise. It is the commonest reason for repeated hospitalizations in the western hemisphere. Although novel ways to manage patients with ischemic CHF have evolved over the past decade, proper identification of patients who are potential candidates for these different treatment options is not performed optimally. The pathophysiology of chronic ischemic LV dysfunction is multifactorial involving previous infarction, post-ischemic dysfunction ('stunned myocardium'), or reduced resting MBF ('hibernating myocardium'), and more than one mechanism can be operative in any individual patient. Thus, the recognition of the specific substrate is very important from the point of view of treatment. We have recently developed a model of chronic ischemic LV systolic dysfunction where all these mechanisms are operative to different degrees. The overall aim of this research proposal is the noninvasive delineation of the mechanism(s) underlying LV systolic dysfunction in different myocardial segments within the same LV, and testing different management strategies for reversing this dysfunction. The studies will be performed in a canine model of chronic ischemic LV dysfunction with special emphasis on recognition of low-flow ischemia versus post-ischemic dysfunction versus non-ischemic dysfunction, and the individual therapeutic strategies for these various conditions. The specific aims of the research proposal are: 1. Accurate noninvasive identification of the specific pathophysiological basis for reduced wall thickening in each dysfunctional myocardial segment. 2. Effect of interventions on Ly dysfunction in relation to the underlying mechanism dysfunction. These interventions include: coronary artery bypass surgery and transmyocardial laser revascularization. 3. Effect of medical treatment in relation to the underlying cause of ischemic LV dysfunction. The drug we will test is carvedilol because of its unique adrenergic inhibitor properties as well as its anti-oxidant and antiapoptotic properties. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CLINICAL PHARMACOLOGY OF LOOP DIURETICS Principal Investigator & Institution: Brater, D C.; Chair; Medicine; Indiana Univ-Purdue Univ at Indianapolis 620 Union Drive, Room 618 Indianapolis, in 462025167 Timing: Fiscal Year 2001; Project Start 01-APR-1988; Project End 31-AUG-2005 Summary: (adapted from Investigator's abstract) During the past grant period, the investigators performed a variety of studies asking clinically pertinent questions about more effective uses of diuretics. In the current proposal, they propose two large new studies that logically extend their previous work. The aim of the first study is to delineate the mechanism of the pharmacodynamic resistance to loop diuretics that occurs in patients with congestive heart failure (CHF). This resistance could occur by increased proximal tubular reabsorption of sodium, increased distal reabsorption of sodium and/or a change in the dynamics of the interaction of the loop diuretic with the Na-K-2Chl transporter of the loop of Henle. The answers to these questions should illuminate the mechanisms of sodium retention in CHF and thus allow more rational

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Congestive Heart Failure

and effective use of diuretic combinations. This study will entail using diuretics with sites of action at different portions of the nephron as probes of this pathophysiology. They will employ methods familiar to them in clinical studies designed to systematically examine the role of different nephron sites in causing diuretic resistance. They will also perform a clinic-based study in which they will attempt to define causes for clinical deterioration in patients with CHF. This study will utilize a unique electronic medical record at the University of Indiana, the Regenstreif Medical Record System (RMRS). This system captures a wealth of clinical data that will be extracted and linked with compliance data, plasma renin and aldosterone activity and quality of life assessments obtained during this study to answer a series of focused questions. Each patient studied will be followed for at least one year. The investigators will perform multivariate analyses to determine causes of clinical deterioration. These data will provide insights into the causes and pathophysiology of decompensation in patients with CHF, thus enhancing our understanding of this increasingly prevalent disease and leading to better therapeutic strategies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: COLLAGENASE INHIBITION IN HEART FAILURE Principal Investigator & Institution: Spinale, Francis G.; Professor; Surgery; Medical University of South Carolina 171 Ashley Ave Charleston, Sc 29425 Timing: Fiscal Year 2001; Project Start 01-JAN-1998; Project End 31-JAN-2006 Summary: (Verbatim from the application): A central component in the development and progression of congestive heart failure (CHF) is left ventricular (LV) remodeling. An important constituent of the LV myocardium is the fibrilIar collagen matrix, which has been proposed to contribute to the maintenance of LV geometry and the structural alignment of adjoining myocytes. An endogenous family of enzymes responsible for extracellular collagen degradation and remodeling is the matrix metalloproteinases, or MMPs. Recent studies have identified increased myocardial expression and activation of certain species of MMPs within the development and progression of CHF. Thus, increased LV myocardial MMP expression and activation are likely contributory mechanisms for the progressive LV remodeling in CHF. The overall goal of this continuing project is to define the mechanisms that contribute to myocardial MMP activation and to develop strategies to inhibit this process with the development and progression of CIIF. Studies will be performed which will address three specific hypotheses regarding the determinants of MMP activity within the extracellular space: transcription, activation and inhibition/deactivation: (1) A local MMP inductionactivation system at the level of the LV myocyte contributes to myocardial MMP activation in CHF; (2) Controlling certain species of MMPs, such as MMP-3 expression and activity, will reduce overall myocardial MMP activity and thereby influence the LV remodeling process with developing CHF; (3) alterations in the endogenous inhibitors of the metalloproteinases (TIMPs) within the LV myocardium contributes to the LV myocardial remodeling process and the progression to CHF. In order to move the findings from these basic studies to clinical applications, this research project will develop high throughoutput and sensitive screening systems for detecting myocardial MMP expression and activity in patients with CHF and define the temporal relation between MMP activation and the LV remodeling process. These diagnostic tools will form the basis by which to identify the therapeutic window for strategies targeted at myocardial MMP inhibition. Through a focused series of integrative studies, contributory cellular and molecular mechanisms that contribute to the LV remodeling

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process with CHF will be identified and therapeutic strategies developed which will slow the progression of this fatal disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

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 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

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Project Title: CYCLIC GMP AND VENTRICULAR FUNCTION IN HEART FAILURE Principal Investigator & Institution: Redfield, Margaret M.; Mayo Clinic Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2001; Project Start 15-JUN-2001; Project End 31-MAY-2004 Summary: The broad objective of this revised application is to define humoral mechanisms that participate in the pathophysiology of asymptomatic ventricular dysfunction (ALVD) and it's progression to overt congestive heart failure (CHF). Our focus is upon cardiac cGMP, a ubiquitous intracellular second messenger whose production is regulated by two systems - the natriuretic peptide system (NPS) and the nitric oxide system (NO). The novel aspect of this application lays in the investigation of the NPS and NO together as a complimentary system which regulates a second messenger whose ultimate level of activation will reflect the cumulative activation of these systems as well as the relative potency of their second messenger signaling. We

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Congestive Heart Failure

will determine the temporal alterations in these two systems and in their combined impact on cGMP during the progression from ALVD to CHF. We will examine the functional consequences of alterations in these systems in respect to regulation of coronary blood flow and myocardial function. Lastly, we will explore the common and disparate mechanisms whereby these complimentary systems alter left ventricular function. Based on preliminary studies, we advance three hypotheses. First, we hypothesize that the NPS and NO are differentially activated during the progression from ALVD to CHF. Second, we hypothesize that through their common second messenger cGMP, these two systems uniquely preserve myocardial blood flow and diastolic function without adverse effects on systolic function. Third, we propose that unlike the NPS, NO possesses additional actions which are independent of its effects on cGMP and which impair systolic function. These studies will enhance our understanding of how these endogenous biochemical mediators influence myocardial perfusion and ventricular function throughout the progression of ALVD to CHF and provide the basis for therapeutic strategies to delay the transition from ALVD to severe CHF. In order to determine whether these complimentary systems are activated, how they modulate cGMP production and whether they ultimately influence myocardial perfusion and ventricular function, studies in the intact dog and in harvested tissue before and during the progression of asymptomatic LV dysfunction (ALVD) to severe CHF are planned and will address the following Specific Aims; Aim 1:Determine if myocardial cGMP and its dual regulators, the NPS and NO systems are activated during the progression from ALVD to severe CHF; Aim 2:Determine whether endogenous NPS and NO modulate myocardial cGMP, coronary blood flow and basal and stimulated LV function during the progression from ALVD to severe CHF; and Aim 3:Determine if the actions of the NPS and NO on basal LV function and beta-adrenergic responsiveness during the progression to CHF are mediated by CGMP. 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

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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 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: DIASTOLIC MECHANISMS

HEART

FAILURE:

DEFINING

CARDIOCYTE

Principal Investigator & Institution: Zile, Michael 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

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Congestive Heart Failure

Summary: The diagnosis of diastolic congestive heart failure (CHF) can be made when patients have symptoms and signs of fluid overload, a normal ejection fraction, and pronounced abnormalities in diastolic function. In a general population of patients with CHF, the prevalence of diastolic CHF is 30-35% and the 5 year mortality rate is 25%. In patients over 70 years old, the prevalence of diastolic CHF increases to 50% and the 5 year mortality rate approaches 50%. Therefore, diastolic CHF is a major health care problem, especially in our aging population. Despite its importance, the basic underlying mechanisms that cause diastolic CHF and the impact that aging makes on these mechanisms are not completely understood. For these reasons, the primary focus of my research has been to define the mechanisms, which cause abnormal diastolic function. Diastolic CHF develops when there has been a fundamental alteration in the passive material properties of the cardiac muscle tissue (i.e., increased diastolic myocardial stiffness). Three of the possible mechanisms which may cause this increase in myocardial stiffness include changes in the cardiac muscle cell (cardiocyte), changes in the extracellular matrix (ECM), and changes in neurohumoral activation. I believe that changes in each of these three mechanisms, individually and in combination, cause the abnormalities in diastolic function that lead to diastolic CHF. Studies examining the ECM and neurohumoral activation are the subject of my ongoing Department of Veterans Affairs Merit Review grant. Studies examining mechanisms within the cardiocyte will be the focus of this Program Project Proposal. The purpose of Project 6 is to prove the hypothesis that basic cardiocyte mechanisms play a significant cause and effect role in the development of the diastolic CHF. This hypothesis will be tested using three specific aims: 1) Determine whether, and to what degree, changes in the viscoelastic properties of the cardiocyte occur in, and are causally related to the increased myocardial stiffness produced by pressure-overload hypertrophy (POH) and advanced age, 2) Define the basic cellular mechanisms which cause increased cardiocyte viscoelastic stiffness, and 3) Determine whether transgenic modulation of these basic cellular mechanisms will prevent or correct the increases in diastolic stiffness produced by POH and advanced age. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DIETARY ETIOLOGIES OF HEART DISEASE AND CANCER Principal Investigator & Institution: Rimm, Eric B.; Associate Professor; Nutrition; Harvard University (Sch of Public Hlth) Public Health Campus Boston, Ma 02460 Timing: Fiscal Year 2003; Project Start 01-DEC-1985; Project End 31-MAY-2007 Summary: (provided by applicant): We propose to continue the biennial follow-up of cardiovascular disease among 51,529 male health professionals, age 40 to 75 years in 1986, to address a series of new dietary hypotheses related to risk of a coronary heart disease and stroke. We project over 4,000 incident MI, fatal CHD, and stroke cases through the end of the follow-up period. Nested within this cohort, over 18,000 participants provided blood samples in 1994 from which we propose to investigate several biological (plasma and genetic) determinants of disease. We will concentrate on several hypotheses related to nutritional and genetic determinants of cardiovascular disease (CVD). With this exceptional resource of repeated assessments of diet and lifestyle characteristics tied to potential genetic markers of disease, we will prospectively evaluate in relation to coronary heart disease 1) n-6 fatty acids across a wide range of n-3 fatty acid intake from fish and vegetable sources, 2) foods with a high glycemic load, specifically among men with a BMI > 25kg/m^2, 3) protein intake as a replacement for carbohydrate, and 4) putative functional variants and haplotypes in candidate genes thought to be insulin targets. Within this metabolic domain we seek to determine if

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lifestyle practices such as physical activity or a low glycemic load diet can modify underlying genetic risk. To investigate further the effect of diet on mediators of CHD we will investigate a) the interaction between n- 3 and n-6 fatty acids on inflammatory risk factors for CVD and b) glycemic load on adiponectin and the associated risk of this adipocyte-derived cytokine on risk of MI and fatal CHD. Also, we propose further to examine aims 1-3 with respect to stroke. Finally, within a small exploratory aim, we propose to document basic risk factors for congestive heart failure by utilizing the innovative methods we designed to study coronary heart disease. The ongoing Health Professionals Follow-up Study will provide follow-up of non-CVD endpoints (CA55075) in addition to information on important covariates for the proposed study. Overall, the large size of the prospective cohort, the high follow-up rate, the repeated assessment of dietary and lifestyle information, and the availability of archived bloods provide a unique cost-effective opportunity to test hypotheses related to CVD risk. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DIRECT METHANOL FUEL CELL ARTIFICIAL HEART POWER SUPPLY Principal Investigator & Institution: Cisar, Alan J.; Manager; Lynntech, Inc. College Station, Tx 77840 Timing: Fiscal Year 2001; Project Start 01-AUG-1999; Project End 31-JUL-2003 Summary: (provided by applicant): Cardiovascular disease is a leading cause of death around the world. Its prevalence is growing with congestive heart failure (CHF) representing the biggest proportion. Current treatment for end-stage CHF is transplantation, but of 40,000 patients in the US under age 65, less than 3,000 will receive transplants in any year. Most patients die while waiting for a transplant. Ventricular assist devices can help some patients as a bridge to transplantation. Implantable artificial hearts will help others, and serve as a permanent solution for patients with rejection problems. For these patients to have a near-normal life requires a compact, high energy density storage system so they can move about freely. Phase I of this SBIR project demonstrated the efficacy of direct methanol fuel cells (DMFCs) in this role. DMFCs consume high energy density methanol solutions (600 Wh/L for a 10 percent solution) at temperatures slightly above ambient and deliver electrical power. DMFC stacks were demonstrated to start at room temperature, heat to operating temperature, and reliably supply electricity with a power density of 53 mW/cm_, requiring only a small fan to supply air and a small pump to deliver fuel as its balance of plant. The stack used to collect this data was fabricated from lightweight materials using standard industrial processes to insure that the final power supply resulting from this project will be manufacturable. PROPOSED COMMERCIAL APPLICATION: Nearly 500,000 people die from congestive heart failure in the US each year, with the total exceeding 3,000,000 around the world. At least half of them could benefit from a TAH or a VAD. These devices are currently in advanced stages of testing with secondary batteries as their only power supply. As they come into wider use higher energy density power supplies will be needed to give these patients a more normal life. This is the market that the proposed power supply addresses. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: EFFECT OF BARIATRIC SURGERY ON INSULIN RESISTANCE & CVD Principal Investigator & Institution: Schauer, Philip R.; Surgery; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260

22

Congestive Heart Failure

Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2008 Summary: (provided by applicant): The study of bariatric surgery offers unique opportunities to evaluate the effects of weight loss among very obese individuals and how this influences quality of life, including impact on co-morbidities of obesity. This proposal is submitted as a collaborative effort of the Department of Medicine, Obesity and Nutrition Research Center (ONRC) and the Department of Epidemiology Prevention Center and Preventive Cardiology Program. We believe that the future studies of bariatric surgery have three important components. First, what is the long term outcome of bariatric surgery in terms of quality of life, morbidity and mortality and are there differences in outcome by type of surgery and characteristics of individuals having the surgery, especially in relationship to distribution of body weight and insulin resistance (IR). The most important health risks for obese individuals are related to cardiovascular disease (CVD). Obesity has been reported to be an independent risk factor for congestive heart failure (CHF) and also for hypertension, type 2 diabetes mellitus, and their complications. Second, the study of bariatric patients offers a unique opportunity to study the metabolic changes associated with obesity and weight loss especially in relationship to carbohydrate and fat metabolism. Third, it is important to try and determine the reasons why many patients can successfully maintain substantial weight loss with minimal co-morbidity after bariatric surgery and especially the potential importance of gastrointestinal physiology and CNS effects on maintaining long-term weight loss. The University of Pittsburgh Bariatric Surgery Program is one of the largest and most successful in the United States. We have excellent follow up of participants and have developed a major collaborative program within the University of Pittsburgh and other institutions. The ONRC is a major National Institutes of Health (NIH)-funded research program dedicated to the study of the pathophysiology of obesity and diabetes and to behavioral research both related to enhancing weight loss and exercise and studying the long term behavioral aspects of these interventions. The Cardiovascular Epidemiology Program in the Department of Epidemiology has extensive experience in observational and clinical trials with a special interest in the measurement of vascular disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ENDOTHELIAL CELL ACTIVATION AND DECOMPENSATION IN CHF Principal Investigator & Institution: Colombo, Paolo C.; Medicine; Columbia University Health Sciences New York, Ny 10032 Timing: Fiscal Year 2002; Project Start 15-AUG-2002; Project End 31-MAY-2007 Summary: (provided by applicant): The candidate, Dr. Paolo C. Colombo, a fourth year cardiology fellow, is completing his training in chronic heart failure (CHF) and vascular biology at the Albert Einstein College of Medicine (AECOM) under the guidance of Dr. Thierry H. Le Jemtel and Dr. J. Anthony Ware. Dr. Colombo is currently supported by an NIH Institutional Training Grant (T32). Dr. Colombo will join the Faculty of the Department of Medicine at AECOM as an instructor in July 2001. Dr. Colombo is most interested in developing new approaches to patient oriented research, taking advantage of his basic science background. The Cardiovascular Division at AECOM with its group of highly productive investigators in heart failure and vascular biology offers an exceptional environment to support Dr. Colombo?s career goals. Dr. Colombo developed a new approach to study the vascular endothelium. Protein expression is quantified by immunofluorescence in 400-900 endothelial cells (EC)s collected with a guide wire inserted in a superficial vein. His preliminary data indicate that transition

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from a decompensated to a compensated state in CHF is associated with a reduction in EC activation and oxidative stress. This application consists of two projects. The first will investigate the hypothesis that EC activation and oxidative stress, precede and contribute to clinical decompensation in patients with CHF. Dr. Colombo will prospectively study compliant patients hospitalized for CHF decompensation not due to co-morbid events. He will monitor markers of EC activation and oxidative stress, plasma cytokines, flow-mediated dilation, renal and cardiac function during decompensation, after return to a compensated state and serially until a second episode of decompensation. The second project will test the hypothesis that a reduction in EC activation and oxidative stress induced by physical training contributes to lowering the risk of CHF decompensation. Patients who experienced a second episode of decompensation in the first protocol will be randomized, once compensated, to routine activity or training. Endothelial cell activation and oxidative stress, plasma cytokines, flow-mediated dilation, renal and cardiac function will be assessed serially for six months or up to the next episode of decompensation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EPIGENETIC MECHANISMS IN DIABETIC CARDIOMYOPATHY Principal Investigator & Institution: Umeda, Patrick K.; Medicine; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 31-AUG-2004 Summary: Applicant's Abstract The broad aim of this research program is to gain insights into the regulatory mechanisms that control the growth and development of cardiac muscle. This proposal examines the role of epigenetic mechanisms in the etiology of diabetic cardiomyopathy. Previous work with a transgenic animal model of cardiac failure and analyses of both animal and human failing hearts suggests that de novo DNA methylation plays an important role in modulating the pattern of gene expression in the heart. In the transgenic model, the methylation of specific gene sequences is sufficient to produce the structural and functional changes of the heart associated with moderate heart failure. These effects of DNA methylation are intrinsic to the heart since the altered heart function in the transgenic model occurs in the absence of cardiovascular disease, hypertension, or any overt developmental defects. In animal and human failing hearts, selective methylation of the same gene sequences is correlated with hypertrophy and congestive heart failure. Preliminary data indicate that similar changes in DNA methylation are found in human diabetic cardiomyopathy. It is postulated that specific gene sequences are methylated de novo in diabetes and that these changes in DNA methylation mediate the structural and functional alterations found in diabetic hearts. To examine this hypothesis, the methylation of specific regions of the genome will be assessed in human hearts diagnosed with diabetic cardiomyopathy. This analysis will reveal if selective sequences are differentially methylated, if the pattern of de novo methylation differs from that observed in failing hearts due to idiopathic cardiomyopathy or coronary artery disease, and if these alterations in methylation reflect more global changes in DNA methylation. To determine whether diabetes itself induces de novo DNA methylation, the temporal changes in DNA methylation following the onset of diabetes will be assessed in an animal model. Finally, the role of specific DNA methylation sites in modulating the heart phenotype will be assessed by a mutational analysis in a transgenic mouse model. Defining a role for DNA methylation in diabetic cardiomyopathy may not only identify a new gene regulatory mechanism for the cardiac effects of diabetes but also would

24

Congestive Heart Failure

provide more insight into novel epigenetic mechanisms that can reprogram gene expression and the phenotype of the heart. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ESCAPE MECHANISTIC SUBSTUDIES Principal Investigator & Institution: Califf, Robert M.; Medicine; Duke University Durham, Nc 27706 Timing: Fiscal Year 2001; Project Start 01-APR-2001; Project End 31-MAR-2004 Summary: (Applicant's Abstract) This proposal is a prospective, observational study designed to evaluate the potential of serum biomarkers to serve both as prognostic indices and as surrogate endpoints for death and hospitalization in heart failure trials. The first goal wlll be accomplished by evaluating relations between levels of natriuretic peptides, troponins, and clinical outcomes. We will develop a risk score for patients with advanced heart failure that incorporates the serum biomarkers and clinical variables and test for interactions between this score and pulmonary artery catheterization. We will also evaluate the ability of serum biomarkers to serve as objective measures of both clinical and hemodynamic status and assess the potential of these markers to serve as tools to assist with the selection and titration of therapies. In addition. we will examine the relations between levels of natriuretic peptides, troponins, and catecholamines. This information will be the launching point for the second goal, which will be to examine the relationship between the serum biomarkers and the treatment effect of pulmonary-artery catheterization on death and hospitalization. In addition, we will evaluate the relations between levels of natriuretic peptides, troponins, and the treatment effects of B-adrenergic antagonists and inotropic agents on clinical outcomes. Ultimately, we intend to construct a statistical model that incorporates the serum biomarkers with greatest promise and clinical variables demonstrated to predict survival. This final model may prove to be the best Surrogate endpoint possible, as it will capture an array of physiological mechanisms through which pulmonary-artery catheter guided therapy may have an effect. This proposed substudy will be conducted within the framework of the ESCAPE trial. Natriuretic peptide levels are currently being collected at randomization, discharge, 1 month, and 6 months as a secondary endpoint of the trial. Catecholamines are also being collected at baseline and 3 months. In addition, the ESCAPE investigators are all ready capturing detailed demographic, clinical, and physiological information as part of the protocol for the primary study. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ETHANOL EFFECTS OF SR CA2+ RELEASE IN CARDIAC MYOCYTES Principal Investigator & Institution: Wasserstrom, J A.; Medicine; Northwestern University Office of Sponsored Programs Chicago, Il 60611 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2006 Summary: (provided by applicant): One of the most serious secondary effects of alcohol abuse is the development of specific alcohol-induced cardiomyopathies which often lead to congestive heart failure. Previous findings suggest that one of the mechanisms underlying reduced cardiac function by ethanol (EtOH) may involve the direct suppression of cardiac excitation-contraction (E-C) coupling. Interestingly, this direct effect does not appear to involve alterations in the trigger for cardiac contraction (via Ltype Ca 2+ current) raising the possibility that the primary negative inotropic effects of EtOH might reside in an altered response to that trigger. The goal of this project is to

Studies

25

investigate how EtOH affects Ca2+ release from internal stores in the sarcoplasmic reticulum (SR) during the cardiac cycle. This will be accomplished through measurement of Ca 2+ sparks, which are thought to represent the fundamental Ca 2+ release units responsible for contraction. The Specific Aims of this project are: 1) to determine if the cardiodepressant effects of EtOH occur as the result of a direct suppression of SR Ca 2+ release; and 2) to investigate whether or not these changes in SR Ca 2+ release contribute to the depression in cardiac function that occurs in a chronic model of alcohol-induced cardiomyopathy. Ca 2+ sparks will be measured in rat ventricular myocytes with the Ca2+-sensitive fluorescent indicator fluo-4 using laser scanning confocal microscopy in combination with whole cell voltage clamp techniques. Some experiments will be performed in saponin-permeabilized myocytes exposed to different cytosolic Ca2+ concentrations in order to assess Ca 2+ sensitivity of Ca 2+ sparks activated purely by Ca 2+ in the absence of functional sarcolemmal Ca 2+ current. These methodological approaches will allow the investigation of how EtOH affects SR Ca 2+ release that occurs both as a result of its normal trigger (L-type Ca 2+ channels) and in response to the final common pathway for E-C coupling, direct activation by Ca 2+. In addition to the study of direct effects of EtOH on the physiological and biophysical processes responsible for SR Ca 2+ release, we will also correlate these changes in SR Ca 2+ signaling with the development of alcohol-induced cardiomyopathy in order to determine if the reduction of cardiac output at the whole organ level occurs as the result of a suppression of E-C coupling at the level of the SR. The results of this study will contribute to our understanding of the mechanisms by which EtOH interferes with SR Ca 2+ release and whether or not this mechanism involves the trigger for E-C coupling or the response to that trigger. More importantly, such information can then be applied to understanding how a reduction in SR function by EtOH might contribute to chronic suppression of overall cardiac function, leading to the development of cardiomyopathies and heart failure associated with long-term alcohol abuse. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: 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

26

Congestive Heart Failure

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 •

Project Title: GENE TRANSFER OF RECOMBINANT ANTIBODY PROTEINS Principal Investigator & Institution: Witztum, Joseph L.; Professor; 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 Summary: Atherosclerosis is a chronic inflammatory disease of the macrovasculature, leading to myocardial infraction as well as heart failure (HF). Oxidation of LDL (OxLDL) leads to its unregulated uptake by macrophages, causing foam cells, the initial lesion of atherosclerosis. OxLDL is also immunogenic, leading to the generation of autoantibodies to epitopes of OxLDL. We have cloned both murine and human monoclonal autoantibodies to OxLDL and shown that when they are radiolabelled and injected intravenously, they target atherosclerotic lesions and that some block the binding and uptake of OxLDL by macrophages. We propose to develop gene transfer techniques that would allow for the systematic expression from ectopic organs, such as liver of muscle, of such recombinant single chain antibodies (scFv) to OxLDL to affect the atherogenic process, for example by blocking OxLDL uptake by macrophages or by delivery to the lesion (which is rich in OxLDL) of important therapeutic molecules. The successful development of these techniques might provide novel therapeutic modalities to retard atherogenesis and improve contractility of the failing heart. There are increasing examples of beneficial effects in humans of the infection of monoclonal antibodies in a variety of different disease states. Therefore, these techniques may be of general utility and could be models by which constant and sufficient delivery of a recombinant antibody could be delivered extracellularly or intracellularly for a wide variety of therapeutic purposes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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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

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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 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: GENETICS STUDIES OF FAMILIAL DILATED CARDIOMYOPATHY Principal Investigator & Institution: Mcnally, Elizabeth M.; Associate Professor; Medicine; University of Chicago 5801 S Ellis Ave Chicago, Il 60637 Timing: Fiscal Year 2001; Project Start 01-FEB-2000; Project End 31-JAN-2004 Summary: Many etiologies lead to the development of dilated cardiomyopathy. Idiopathic dilated cardiomyopathy arises from intrinsic muscle disease in the presence of normal coronary arteries and the absence of a clear toxic or immunologic insult. Approximately 30 percent of idiopathic dilated cardiomyopathy patients have first degree relatives that also show evidence of cardiac dilatation with or without symptoms of congestive heart failure. Supporting this, genetic loci have been significantly associated with familial dilated cardiomyopathy (FDC). Positional cloning efforts are underway to increase our understanding of the molecular mechanisms that underlie familial dilated cardiomyopathy. Through genetic linkage analysis, we have identified a region of chromosome 6q23 that is associated with dilated cardiomyopathy, conduction system disease that produces progressive atrio-ventricular block and a mild, adult onset, slowly progressive muscular dystrophy. We have constructed a physical map of this region of chromosome 6 and evaluation of candidate genes is underway. We have also discovered a second region, chromosome 2q22, that is associated with dilated cardiomyopathy and ventricular arrhythmias. We propose to refine the genetic interval, identify candidate genes and, through mutation analysis, identify the gene responsible for chromosome 2-associated FDC. The FDC-gene product will be studied for expression patterns in both normal and diseased tissue. The murine homolog of the FDC-gene will be determined. We will also establish a clinical and DNA database of dilated cardiomyopathy patients. This database will be used to determine the role of certain mutations in the development of the cardiomyopathic process. While genetic heterogeneity is present in FDC, the study of genes responsible for this disorder will

28

Congestive Heart Failure

reveal whether multiple cellular mechanism lead to cardiomyopathy. Additionally, in families with dilated cardiomyopathy, we find a prodrome of arrhythmias prior to the onset of cardiac dilatation and congestive heart failure. By developing genetic markers, we will identify those at risk for arrhythmia and most like to benefit from pacemaker and/or implantable defibrillator treatment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: 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: GLUCOSE METABOLISM IN HYPERTROPHIED HEART IN ISCHEMIA Principal Investigator & Institution: Del Nido, Pedro J.; Professor of Surgery and Chair; Children's Hospital (Boston) Boston, Ma 021155737 Timing: Fiscal Year 2001; Project Start 01-APR-2000; Project End 31-MAR-2004

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Summary: Myocardial hypertrophy remains an important risk factor for pediatric cardiac surgery of congenital and acquired heart disease. Clinical and experimental studies have shown that hypertrophied myocardium exhibits a worse recovery of contractile function post-ischemia. Glucose transport/utilization by myocytes is critical for normal function, and during ischemia and early reperfusion. Exogenous glucose for glycolysis enters the cell via a transporter protein (GLUT-1 and 4 in the heart), and at physiologic glucose concentrations, glucose entry into the cell is rate-limiting for its subsequent metabolism. Using a model of pressure overload hypertrophy (aortic banding at 10 days of age), we have shown that in hypertrophied hearts, glucose transport across the sarcolemma in response to insulin is impaired and this change is associated with worse recovery after ischemic injury. Inversely, improving glucose uptake significantly improves post-ischemic recovery in hypertrophied hearts. We therefore hypothesize that impaired glucose transport into myocytes is in large part responsible for the decreased tolerance of hypertrophied myocardium to ischemia. Insulin insensitivity, with resultant lack of activation of glucose transporters and downregulation of glucose transporter expression occurs in conjunction with the development of uncompensated hypertrophy. Proteins such as tumor necrosis factor which are elevated in congestive heart failure, can inhibit insulin response and cause downregulation of glucose transporters in myocytes. The overall goal of this project is to increase our understanding of the role and mechanism responsible for decreased glucose uptake in hypertrophied myocardium and to develop novel therapies to improve tolerance to ischemia. The P.I. has brought together a multidisciplinary group of investigators with expertise in the various aspects of the project. We will pursue three specific aims to determine the mechanism responsible for insulin insensitivity in the hypertrophied heart (AIM I); test the efficacy of interventions aimed at bypassing the functional defect in insulin signaling (AIM II); and determine the effect and mechanism of action of tumor necrosis on glucose uptake and glucose transporter expression in cardiac myocytes in culture (AIM III). We will use a model of pressure overload hypertrophy generated by aortic banding of neonatal rabbits. Non-invasive assessment of LV muscle mass with trans-thoracic echocardiography will be used to monitor the development of hypertrophy and progression to heart failure. The hearts will be studied after the development of moderate and severe hypertrophy in an isolated blood perfused heart preparation. We will also perform studies using cardiomyocytes in culture to determine the mechanism responsible for glucose transporter downregulation. 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 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

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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 IN THE COMMUNITY Principal Investigator & Institution: Roger, Veronique L.; Mayo Clinic Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2003; Project Start 15-JAN-2003; Project End 31-DEC-2006 Summary: (provided by applicant): Heart failure (HF) is designated as an emerging epidemic. Yet, it is not fully characterized. Most data, derived from hospital discharges, cannot measure incidence, have uncertain validity and cannot capture the full burden of HF because of the shift towards outpatient care. Regarding its etiology, the respective role of hypertension and coronary heart disease (CHD) is controversial. Moreover, the prevalence of obesity and diabetes mellitus is increasing, both conditions linked to HF via several mechanisms such that their contribution to HF could conceivably be increasing but remains to be examined. Finally, while the existence of diastolic HF is recognized, its diagnosis is exclusionary based on symptoms of HF in the absence of LV systolic dysfunction. This approach is unsatisfactory, thus the contribution of DHF to HF remains contentious. These striking gaps in knowledge underscore the necessity of a rigorous investigation of the HF epidemic. Through surveillance of the Olmsted County community, we demonstrated the postponement of CHD towards older ages and the decline over time in the severity of hospitalized MI and the incidence of HF after MI. This implies that, if CHD is the main cause of HF, HF should be postponed towards older ages and its incidence rate relatively stable. During the same period, preliminary findings on HF surveillance suggest that the incidence of first clinical diagnosis of HF may not be increasing as much as implied by hospital discharges and that adverse trends may be occurring preferentially among younger ages. These data from the same community are challenging to reconcile with the concept of an ongoing major contribution of CHD to an epidemic of HF, thereby underscoring the need to rigorously

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study the epidemiology of HF, which is the focus of this application. We propose 3 specific aims and a community surveillance approach, integrated with our ongoing work on CHD surveillance to investigate the HF epidemic in Olmsted County by characterizing its magnitude and determinants and studying prospectively the contribution of DHF. Aim 1 will estimate the secular trends in the incidence and in the outcome of validated HF to test the hypotheses that there has been an increase in the incidence of HF, which differs by age and sex and that the survival of HF improved while hospitalization for HF has increased. Aim 2 will use a case-control approach to characterize the etiology of HF and its changes over time to test the hypotheses that CHD and hypertension confer an excess risk of HF, the magnitude of which is declining over time, that obesity and diabetes mellitus confer an excess risk of HF the magnitude of which is increasing and that the population attributable risk of CHD and hypertension for HF is declining, while that of obesity and diabetes mellitus is increasing over time. Aim 3 will prospectively characterize the contribution of DHF to HF using brain natriuretic peptide (BNP) among persons with HF and define the prognostic value of BNP in all cases of HF. Thus, the completion of these aims will provide important insights into the epidemiology of HF. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HOMING AND GENETIC MODIFICATION OF MESENCHYMAL STEM CELL Principal Investigator & Institution: Dzau, Victor J.; Chairman; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2007 Summary: (provided by applicant): Coronary vascular occlusion can lead to myocardial infarction with subsequent loss of myocardial cells, and eventual scar formation. The consequence is loss of muscular function that can lead to congestive heart failure and possibly, death. Numerous attempts have been made to regenerate cardiac vessels and the myocardium. It has been demonstrated that bone marrow-derived stem cells migrate to the injured myocardium and then differentiate into both endothelial and myocardial cells, with partial restoration of cardiac function. We and others have shown that mesenchymal stem cells (MSCs) may participate in cardiac repair after intramyocardial injection. Based on the hypothesis that specific signals are responsible for the homing and adherence of MSCs to myocardium and subsequent engraftment in the myocardium, we propose to study the following specific aims: 1) to optimize the conditions for isolation of MSCs that have capacity to differentiate into cardiac myocytes, and to further characterize these MSCs 2) to determine the chemical signals and adhesion receptors that mediate homing of MSCs to ischemic myocardium; 3) to further enrich for the sub-set of MSCs that expresses receptors/ligands that mediate specific myocardial homing and to genetically modify these MSCs so as to enhance homing and adhesion to the ischemic myocardium, 4) to determine whether systemic delivery of enriched and/or modified MSCs is a superior strategy to systemic delivery, or direct intra-myocardial delivery of non-modified MSCs for purposes of cardiac regeneration and recovery of cardiac function. Since the phenotype of MSCs that differentiate into cardiac myocytes is uncertain, we plan to optimize conditions for the isolation of MSCs that differentiate into cardiac myocytes, and to further characterize the "signature" of this sub-population of MSCs. Using genomics and proteomics, we will then screen which cytokines and adhesion receptors are upregulated in the ischemic myocardium, and whether these cytokines can be used to enhance trafficking and homing of MSCs to the myocardium. Having identified cytokines and adhesion

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receptors integral to the homing and engraftment process, we will perform genetic manipulations on MSCs (for example, to over express cytokine receptors or specific adhesion ligands) and determine whether this strategy will enhance viability, homing and engraftment of MSCs to the ischemic myocardium. Finally, we will examine if systemic administration of genetically modified MSCs is a superior therapeutic strategy to direct intramyocardial injection for cardiac repair and regeneration. Such specific manipulations to enhance the process of homing and engraftment to the myocardium will improve therapeutic options for ischemic heart disease and congestive heart failure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HUMAN ALBUMIN THERAPY OF ACUTE ISCHEMIC STROKE Principal Investigator & Institution: Ginsberg, Myron D.; Professor; Neurology; University of Miami Box 248293 Coral Gables, Fl 33124 Timing: Fiscal Year 2001; Project Start 15-AUG-2001; Project End 31-JUL-2004 Summary: In this revised NINDS Pilot Clinical Trial Grant for Neurological Disease, we propose to conduct a phase I investigation of intravenous human serum albumin therapy (HSAlb) for the treatment of acute ischemic stroke. The study is structured as an open-label, non-randomized dose-finding trial that will be conducted at two clinical sites - the University of Miami/Jackson Memorial Hospital and the University of Calgary/Foothills Medical Centre, Canada. Both sites are major University-affiliated teaching hospitals with active Stroke Services and state-of-the-art facilities. The Department of Biometry and Epidemiology at the Medical University of South Carolina, Charleston, will provide data management and statistical analysis. The study's primary objective is to employ a multiple-tier dose-escalation design to discern the safely tolerated maximum dose and administration of intravenous HSAlb in patients with acute ischemic cerebral infarction of 8 hours' duration or less; and to implement standardized procedures for monitoring cardiovascular function and assessing neurological outcome. Our secondary objective is to evaluate neurological and functional outcome at 1 and 3 months after hospital discharge in order to obtain pilot experience for future randomized, multicenter phase II-III trials of this agent. Two patient subgroups will be separately and independently studied: those admitted with 3 h who also receive tissue plasminogen activator therapy, and those not receiving tPA. The study's hypothesis is that patients with acute ischemic stroke will tolerate moderate doses of HSAlb without suffering cardiovascular complications or other adverse events. Eligibility criteria include entry within 8 hours; initial NIH Stroke Scale of 6 or greater; and age =greater than 18 years. Major exclusion criteria include congestive heart failure, reduced cardiac ejection fraction by echocardiography, intracranial hemorrhage, severe hypertension, and serious systemic disease. In extensive preclinical studies, we have documented that human albumin therapy confers consistent, marked neuroprotection in animal models of both focal and global brain ischemia as well as in acute brain trauma. We have shown that the therapeutic window for neuroprotection with moderate- dose albumin (1.25 g/kg) extends to four hours after onset of MCA occlusion, and that this albumin dose, when given 2 hours after stroke onset, reduces infarct size even in permanent MCA occlusion. This proposed clinical trial is unique in permitting the opportunity to study this highly efficacious agent at a dose and administration that closely resemble the experimental settings in which its efficacy has already been proven. In our view, the multiple unique physiochemical properties of the albumin molecule are integral to its neuroprotective effect and render it uniquely suited as a therapeutic agent to combat ischemic brain injury.

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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IMPROVED ACTIONS OF NITRATES AND STATINS WITH LARGININE Principal Investigator & Institution: Caldwell, Ruth B.; Professor; Nitrosystems, Inc. 512 Telfair St Augusta, Ga 30901 Timing: Fiscal Year 2003; Project Start 01-FEB-2003; Project End 31-JAN-2004 Summary: (provided by applicant): This project seeks to develop safer, more effective and enduring: 1) nitrate therapy for angina and congestive heart failure using nitroglycerin (GTN) or isosorbide mononitrate (ISMN) and 2) statin therapy [pravastatin (PRA) or simvastatin (SIM)] for unstable angina and stroke, by their combination with L-arginine (L-arginine). Nitrovasodilators are highly effective acutely, but their usefulness for chronic therapy is limited due to the rapid development of tolerance to their vasodilating effects. NitrOSystems, Inc. has discovered an additional endothelial cell (EC)-dependent mechanism of GTN-induced vasodilation and tolerance and that tolerance can be prevented by treatment with supplemental L-arginine. Data show that GTN activates EC nitric oxide synthase (eNOS) to produce NO from its substrate Larginine. It is known that the intracellular supply of L-arginine can become limiting in diseases characterized by vascular dysfunction, that diminished availability of Larginine as a substrate for eNOS can result in EC damage due to formation of superoxide anion (SOA) and other reactive oxygen species and that treatment with supplemental L-arginine can prevent EC dysfunction. Statins or HMG CoA reductase inhibitors, by mechanisms unrelated to lowering lipids, activate eNQS and inhibit platelet aggregation. Formation of SOA is also increased by statins. It is hypothesized that sustained elevated extracellular levels of L-arginine are required for optimal therapeutic effects of nitrates and the statins and that supplemental L-arginine will potentiate drug actions by reducing formation of SOA. Specific aims are to: 1. Determine the ability of GTN, ISMN, PRA, SIM to activate NOS and produce SOA in EC and the ability of supplemental L-arginine to prevent SOA formation. 2. Determine the ability of supplemental L-arginine to prevent SOA formation and nitrite tolerance in animals. 3. Develop an IV formulation of GTN in combination with L-arginine and an oral combined sustained release formulation of ISMN and L-arginine. 4. Develop an oral combined sustained release formulation of SIM and L-arginine. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: INHIBITOR AMELIORATES OXIDATIVE AND PROTEOLYTIC STRESS Principal Investigator & Institution: Tyagi, Suresh C.; Associate Professor; Physiology and Biophysics; University of Louisville University of Louisville Louisville, Ky 40292 Timing: Fiscal Year 2003; Project Start 05-SEP-2003; Project End 31-AUG-2008 Summary: (provided by applicant): Endocardial endothelial (EE) dysfunction and accumulation of oxidized-matrix between endothelial and muscle are the hallmarks of congestive heart failure (CHF). The overall objective of this project is to understand the mechanism of oxidized-matrix accumulation and EE dysfunction in CHF. Previous studies have suggested an association between induction of oxidative stress, decrease in endothelial cell density, activation of matrix metalloproteinase (MMP), collagenolysis, and repression of cardiac tissue inhibitor of metalloproteinase (CIMP) in CHF. The novelty of this proposal is that among all known tissue inhibitors of metalloproteinase (TIMP), the TIMP-4 (i.e. CIMP) is highly expressed in the heart. The purpose of this

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proposal is to test a central hypothesis that oxidized-matrix accumulation and EE dysfunction are due to increased levels of MMP activity, and collagenolysis. These levels are associated with decreased levels of EE nitric oxide, and CIMP in response to increased levels of reactive oxygen species (ROS) during protracted cycles of ischemia/reperfusion in volume overload. The increased levels of CIMP protects EE against oxidative and proteolytic stresses. We will test the central hypothesis by the following three specific aims: 1. To determine whether CIMP decreases oxidative stress by increasing EE nitric oxide concentration. Plasma and left ventricle levels of nitric oxide, ROS, and nitrotyrosine will be measured in chronic volume overload arteriovenous fistula mice treated with and without CIMP. 2. To determine whether CIMP protein transfer inhibits collagenolysis. MMP activity will be measured by in situ zymography. The levels of CIMP activity will be measured by reverse zymography. Total collagen and its degradation fragments will be measured by Western-blot analysis using anti-collagen antibody. 3. To determine whether CIMP ameliorates endocardial endothelial dysfunction. Contractile responses to acetylcholine, bradykinin, and nitroprusside in cardiac rings will be measured in a tissue myobath. These studies will enable us to determine whether CIMP improves the hearts response to nitric oxide donors. Identification of major players involved in the control of oxidative and proteolytic stresses will help to develop strategies to prevent CHF. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INNATE IMMUNITY AND MYOCARDIAL INJURY Principal Investigator & Institution: Bourcier, Todd M.; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 05-FEB-2000; Project End 31-JAN-2004 Summary: Both humans and experimental animals with heart failure exhibit increased expression in the heart of inflammatory cytokines, including TNF, IL-1beta and IL-6, as well as iNOS, in the absence of evidence of infection. While maladaptive cardiac remodeling has been attributed to these proteins, the proximal events that trigger and sustain their expression are not well understood. Each of these mediators, however, are now known to be related to innate immunity, an evolutionarily ancient arm of the immune system that is triggered by pattern recognition receptors (PRRs), such as the toll-like receptors (TLRs) expressed by invertebrates and vertebrates, that recognize largely invariant structural motifs on pathogens. It is now recognized that innate immune PRRs also may have evolved in eukaryotes to recognize and repair or remove injured or dying cells, again by recognizing relatively invariant motifs found on injured cells or on cells programmed to die. Based on these observations and our own preliminary data, we hypothesize that vertebrate TLR4, which is expressed by cardiac myocytes, plays a pivotal role in the response to injury in the heart. Specifically, we will examine: 1) the regulation of TLR4 expression in cardiac myocytes in vitro in response to injury induced by UV light, by anthracycline antibiotics and by cyclic biaxial strain coupled with electric field pacing, as well as in cardiac myocytes in situ in remodeling murine ventricular muscle following experimental myocardial infarction; 2) the signal transduction pathways leading to NFkappaB and MAP kinase activation by activated TLR4 in cardiac myocytes and their possible localization to caveolar microdomains; and 3) the functional role(s) of TLR4 in the response to myocyte injury in vitro and in vivo; specifically, we will test the hypothesis that: i) a constitutively activated TLR4 construct conveys a survival signal in vitro; ii) that TLR4 participates in the recognition and removal of apoptotic cells; and iii) that animals with targeted disruption of TLR4, or of

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its immediate downstream signaling target MyD88, exhibit altered rates of ventricular remodeling in response to myocardial infarction. 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 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

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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: 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 stressfree state of the ventricle during the transition from dilation to failure, and use mathematical models to predict subsequent abnormal changes in diastolic and systolic wall stresses. (3) We expect that changes in. regional myocyte orientation, both at the cellular and global levels, are mechanisms of cardiac dilatation and failure. To test this hypothesis, local myocyte disarray and regional variations in laminar sheet orientation will be measured during the transition to failure. We will incorporate these measures

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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 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

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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: MR DIAGNOSIS OF MUSCLE METABOLISM AND FUNCTION Principal Investigator & Institution: Kushmerick, Martin J.; Professor; Radiology; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2001; Project Start 01-FEB-1993; Project End 31-JAN-2003 Summary: The goal of this project is to develop diagnostic procedures for human muscle function using 31-P/1-H NMR spectroscopy and 1-H NMR imaging together with principles of energy balance developed in the first grant period. The applicants working hypothesis is that integration of energy balance provides mechanistic information essential to define normal and to interpret abnormal muscle function in the intact human limb. The first three specific aims develop the notions of an integrative mass and energy balance. PCr content measures the supply-demand balance between muscle ATPases and oxidative phosphorylation. Myoglobin desaturation measures the supplydemand balance between oxidative phosphorylation and muscle perfusion. Intracellular pH and lactate measures the balance between net glycolytic flux and washout by perfusion. The contractile economy in human limb muscles will be quantified by characterizing the ATPase due to myofibrillar force generation and to excitationcontraction coupling. Whether PCr level during exercise is the link between local perfusion and O2 demand will be tested and the magnitude and time course of the glycogenolytic flux during exercise will be quantified. The fourth specific aim will probe

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two clinical problems for imbalances in one or more components of muscle energetics. Patients with congestive heart failure will be probed for abnormalities in ATP, H+ and oxygen balances and patients with type 1 diabetes will be probed for a trade-off in abnormalities resulting in lower functional, but near-normal integration of muscle energetics. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NEUROHORMONAL HYPERTENSION

ACTIVATION

IN

PULMONARY

Principal Investigator & Institution: Kawut, Steven; Medicine; Columbia University Health Sciences New York, Ny 10032 Timing: Fiscal Year 2001; Project Start 01-SEP-2001; Project End 31-AUG-2006 Summary: Candidate's Plans/Training: The candidate plans a career as an independent clinical investigator focusing on patient-oriented research related to pulmonary vascular disease. Training will include formal epidemiological course work in clinical research and closely mentored completion of the research protocol. Environment: The Center for Clinical Epidemiology and Biostatistics (CCEB) will provide formal coursework and structured mentoring. The CCEB, Pulmonary Vascular Disease Program, and General Clinical Research Center at the University of Pennsylvania Medical Center will provide research support. Research: Primary pulmonary hypertension (idiopathic) and secondary pulmonary hypertension (associated with portal hypertension, anorectic use, HIV, scleroderma, and other collagen vascular diseases) cause substantial morbidity and mortality. Although there are available therapies and interventions, they may be costly and risky in themselves. In addition, targeting therapy at the mechanism of morbidity and mortality and distinguishing highrisk patients have been suboptimal. There is evidence that certain vasoactive substances may play an important role in the disease process of pulmonary arterial hypertension. Studies have documented elevated levels of endothelin, natriuretic peptides, and norepinephine in patients with this disease. It is well known that these neurohormones play important mechanistic and predictive roles in left-sided heart failure. Similarly, there is much potential for these neurohormone levels in determining 1) the mechanism of disease and 2) the prognosis in pulmonary arterial hypertension. We propose an investigation of patients with pulmonary arterial hypertension to examine whether levels of these biomarkers at baseline and at six month follow-up are associated with right-sided heart failure and cardiovascular death. We will formulate prediction rules using neurohormone levels and clinical variables to improve prognostication and management in this disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: OCCLUDED ARTERY TRIAL DATA COORDINATING CENTER Principal Investigator & Institution: Knatterud, Genell L.; President; Maryland Medical Research Institute, Inc 600 Wyndhurst Ave Baltimore, Md 21210 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 31-AUG-2004 Summary: Current pharmacologic strategies fail to achieve effective reperfusion in 30 percent or more of acute myocardial infarction (MI) patients, and many patients with occluded infarct-related arteries (IRAs) do not meet current criteria for use of these agents. Early angioplasty, an effective reperfusion method, is available to a small proportion of potentially eligible acute MI patients in the U. S. Hence, a substantial number of acute MI patients pass the time when reperfusion therapy has well documented benefit (12-24 hours) with a persistently closed IRAs. Several lines of

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Congestive Heart Failure

experimental and clinical evidence suggest that late reperfusion of these patients could provide clinically significant reductions in mortality and morbidity. Hypothesis. Opening an occluded IRA 3-21 days after an acute MI in high-risk asymptomatic patients (ejection fraction less than 50 percent or proximal occlusion of a large coronary artery) will reduce the composite end point of mortality, recurrent MI, and hospitalization for NYHA Class IV congestive heart failure (CHF) over an average 3year follow-up. Study aims. In the Open Artery Trial (OAT) 3,200 patients will be randomly allocated in equal proportions to the two treatments over two years. One treatment will consist of conventional medical management (including aspirin, beta blockers, ACE inhibitors, and risk factor modification). The experimental treatment will consist of conventional medical therapy plus percutaneous coronary intervention and coronary stenting. The primary specific aim is to compare the composite outcome of allcause mortality, non-fatal MI and hospitalization for Class IV CHF based on an average 3-year follow-up among patients assigned to the two treatments. Three secondary specific aims are to compare: 1) the individual components of the study composite primary end point in the two treatments; 2) the medical costs of the two treatments; and 3) health-related quality of life in the two treatments. Role of Data Coordinating Center. This application is made for support of a Data Coordinating Center (DCC) at the Maryland Medical Research Institute. The DCC is responsible for statistical design and power calculations, random treatment assignments, data management, support for the Mortality and Morbidity Classification Committee, rapid communication and generation of performance data for review with the Study Chair and Co-Chair of the Clinical Coordinating Center and data analysis to assess treatment effects. 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

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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 •

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 wellestablished 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

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Project Title: PEDIATRIC CARDIOMYOPATHY REGISTRY Principal Investigator & Institution: Lipshultz, Steven E.; Professor; Pediatrics; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2001; Project Start 30-SEP-1995; Project End 31-AUG-2004 Summary: The Pediatric Cardiomyopathy Registry (PCMR) has become a registering center for children with cardiomyopathy, one of the leading causes of morbidity and mortality in infants and children. We maintain the PCMR for children with different forms of cardiomyopathy in order to collect and organize relevant clinical and demographic information as an active and available resource for clinicians and scientists, allowing for increased awareness and knowledge of pediatric cardiomyopathy and its causes and the development of new diagnostic and therapeutic approaches. We are applying for continued funding of the PCMR to foster increased

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Congestive Heart Failure

understanding of this devastating clinical problem that is not being addressed by any other study or organization. We will address important questions that have not yet been adequately studied. This study will draw on the strength of our current cohort of well characterized patients as a natural history study and also expand prospective data collection within restricted regions with complete capture of population- based cases. We propose 3 primary specific aims: l. To confirm whether the regional, ethnic group, time gender, age, and type of cardiomyopathy differences in the incidence of cardiomyopathy observed in the PCMR are correct by prospectively capturing two distinct regions of the United States; 2. To determine whether baseline factors at diagnosis or trends over time predict outcomes of mortality, late abnormalities of ventricular structure and function, congestive heart failure, listing for cardiac transplantation, Or receiving a cardiac transplantation; 3. To assess the functional status of children with cardiomyopathy. Our primary hypotheses are that: 1. During the period of the registry, the percentage of pediatric cardiomyopathy Cases that are diagnosed as idiopathic will decrease (i.e., etiologies will be found for a larger percentage of cases, and 2. At the time of diagnosis of cardiomyopathy, factors such as gender, ethnic group, age, type of cardiomyopathy, and presence or absence of a syndrome can help predict outcomes, such as the need for medical management, the need for surgical management (transplant), or the failure of both medical and surgical management (death). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PEDIATRIC HEART DISEASE NETWORK: CHOP MEMBERSHIP Principal Investigator & Institution: Vetter, Victoria L.; Children's Hospital of Philadelphia 34Th St and Civic Ctr Blvd Philadelphia, Pa 19104 Timing: Fiscal Year 2001; Project Start 01-SEP-2001; Project End 31-AUG-2006 Summary: (provided by applicant) As a Clinical Center in the new Pediatric Heart Disease Clinical Research Network (PHDCRN), the Children?s Hospital of Philadelphia (CHOP) will participate collaboratively with the Network to improve outcomes for children with heart disease, provide an evidential base for therapies currently used or considered, develop new therapies, and disseminate that information to the medical community. To achieve this goal, we will address the following aims: Aim 1: Develop an infrastructure and investigational team for to assure full participation in PHDCRN; Aim 2: Develop procedures and policies to assure proper implementation of approved PHDCRN protocols; Aim 3: Fully participate in the development new protocols and dissemination of information to the scientific community. Two protocols are proposed for the PHDCRN?s scientific agenda that emphasize the research strengths of the Cardiology Division, the Cardiac Center and CHOP. The short-term study investigates the use of biventricular pacing or cardiac resynchronization in children with severe congestive heart failure and dilated cardiomyopathy. The primary aim of the study is to evaluate the acute effects of biventricular pacing on cardiac function as measured by oxygen consumption during exercise in a 6-week randomized controlled clinical trial. After the 6-week randomized comparison, all patients are paced and longer-term effects on cardiac function, functional capacity and quality of life will be evaluated out to 12 months. The long-term project investigates whether enalapril (ACE inhibition) can reduce the time-related decline in exercise performance experienced by patients with single ventricle who have undergone the Fontan procedure. The primary aim will be to evaluate the effects of ACE inhibition over a 4-year period on maximal oxygen consumption measured during exercise testing in a double blinded randomized clinical trial design. The Children?s Hospital of Philadelphia Cardiology Division and Cardiac Center has a distinguished history of clinical innovation and excellence in cardiac care, a

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high volume program with expertise in all areas of pediatric cardiology including cardiac arrhythmias, echocardiography, exercise physiology catheterization including interventions, intensive care, cardiac magnetic resonance imaging, transplantation, and surgery for heart disease. Patient care is integrated through a multidisciplinary Cardiac Center. The faculty of the Cardiac Center are experienced investigators and maintain a highly productive program of multicenter and institutional clinical trials and studies. CHOP has made major investments in the clinical research infrastructure that support essential functions in clinical investigations. These programmatic and institutional strengths support the aims and enhance the likelihood that the long-term goals of the PHDCRN will be achieved. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: POTASSIUM AND THE MUSCLE REFLEX IN HUMAN SUBJECTS Principal Investigator & Institution: Daley, Joseph C.; Medicine; Pennsylvania State Univ Hershey Med Ctr 500 University Dr Hershey, Pa 17033 Timing: Fiscal Year 2001; Project Start 01-APR-2001; Project End 31-MAR-2006 Summary: PROPOSAL (Adapted from the applicant's abstract): The long-term goal of the principal investigator (PI) is to become a clinician scientist examining issues pertaining to autonomic regulation in health and disease. The main objective of this project is to examine the metabolic and mechanical factors that initiate and sustain the muscle exercise pressor reflex. This reflex is a major determinant of blood flow and pressure during exercise. In addition, diseases, such as congestive heart failure (CHF) are associated with pathologic activation of this reflex and may contribute to the morbidity and mortality of this common disorder. Two basic theoretical components of neural control of circulation predominate. "Central command," a feed forward signal emanating from the central motor areas, suggests that neural motor and sympathetic activation occur in parallel. This system may be integrally linked to skeletal muscle metabolic demand. The second component of the reflex is the muscle reflex, and is the subject of this investigation. It is clear chemical byproducts of muscle contraction can evoke a pressor response. However, the specific interstitial chemical(s) that stimulate the muscle fiber afferents, and engage the reflex, remains an area of considerable controversy. This study proposes investigation of the relationship between interstitial potassium concentration and muscle sympathetic nervous activity (MSNA). Recent studies have implicated potassium as a potential mediator of the muscle reflex; however, conclusive evidence linking interstitial K+ with MSNA does not exist. The investigators will examine the "real time" interstitial concentration of potassium in exercising muscle and MSNA simultaneously, as well as venous plasma effluent, to further our understanding of this relationship. In addition, they propose examination of the exercise pressor response after directly inhibiting Na+/K+ pump with regional digoxin administration. This project will further increase their knowledge of the mechanisms regulating the muscle exercise pressor response, and may add to understanding of the role of this reflex in diseases such as CHF. The PI has been funded by an NRSA (F32 HL10320). This proposal will give the PI the additional support and training necessary to become an independent investigator. The mentor for this project has recently received a K24 Award and is the Program Director (PD) of their General Clinical Research Center (GCRC). Accordingly, he is ideally suited to serve in this capacity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PREDICTING DEPRESSION OUTCOMES IN MEDICALLY ILL ELDERS Principal Investigator & Institution: Koenig, Harold G.; Associate Professor; Psychiatry; Duke University Durham, Nc 27706 Timing: Fiscal Year 2001; Project Start 15-AUG-1999; Project End 31-JUL-2004 Summary: Older adults with congestive heart failure (CHF) and chronic pulmonary disease (CPD) are increasing in number. Their lives and ability to function are greatly affected by these illnesses, which frequently lead to recurrent hospital admissions to manage exacerbations. We have found that 26 percent of older persons with CHF or CPD fulfill criteria for major depressive disorder when hospitalized. Depression is often prolonged, affects recovery, and increases use of health services. About one-third of these depressed patients, however, will go into full remission within three months of hospital discharge, often without specific treatment for depression. Many of these patients improve because their physical illness improves. The other two-thirds of depressed patients will have persistent depression, whether or not their health improves. Minor depression is even more common than major depression, being present in 32 percent of such patients, and while it may have a better prognosis than major depression, it is nevertheless associated with considerable disability and poorer quality of life. Research Questions: We are interested in studying four conjoint trajectories of depression-physical health outcome in the first six months after hospital discharge: depression and health both improve, depression improves but health does not, health improves but depression does not, and neither depression nor health improves. What proportion of patients follow each trajectory? What psychosocial and health characteristics predict which trajectory they will follow? What are the barriers to effective treatment, how is depression currently treated in these patients, and what are predictors of treatment intensity? Methods: 1000 older patients with CHF or CPD and major (n=500) or minor depression (n=500) will be recruited from the inpatient services of Duke Hospital and two community hospitals and followed for six months after discharge. Detailed assessments of depression and severity of medical illness will be conducted by a research nurse during telephone and in-person evaluations. Significance: Such information is necessary to determine which of the many patients with major or minor depression need specific treatment, and which patients will improve on their own after discharge as their medical illness improves or fails to improve. It will also provide important information to both guide future clinical trials and identify barriers to effective treatment of depression in these patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PREDICTIONS & OUTCOMES IN CONGESTIVE HEART FAILURE Principal Investigator & Institution: Poses, Roy M.; Director of Research; Virginia Commonwealth University Richmond, Va 232980568 Timing: Fiscal Year 1990; Project Start 01-APR-1990; Project End 31-MAR-1997 Summary: Intensive care units (ICU's) are a dramatic and ever more expensive part of the health care system. However they may be used inefficiently. Physicians may admit acutely ill patients to ICU's who will never require their specialized services. In addition, doctors may fail to admit acutely ill patients whose condition rapidly deteriorates outside of these units, and who may have benefited from being in one. To improve the likelihood that the patients most in need of intensive care are the ones who receive it, several distinguished committees and researchers have proposed guidelines for admission to ICU's. In the absence of an immediately life- threatening condition that

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can only be treated within an ICU they suggest that decision-making should depend ont he probabilities of these outcomes: that the patient will soon develop such a condition, will survive short- term, and will make a "reasonable recovery." However, physicians working with limited information may not be able to make accurate and discriminating predictions of these outcomes for acutely ill patients prior to the triage decision. There are no valid models available to predict these outcomes, although prior experience suggests that it would be feasible to develop them. Therefore, the major goals of this study are to: 1) assess the quality of physicians' predictions of these outcomes of acute illness that should be most relevant to their initial triage decisions, and to 2) develop multivariable models to predict these outcomes, and validate them by comparing their performance with that of physicians' estimates on an independent patient sample. Minor goals include assessing 3) whether the quality of physicians' predictions may be unfavorably influenced by cognitive biases or the inappropriate use of heuristics; 4) whether variability in physicians' decisions may result from variability in how they weight patient variables and institutional factors, both appropriate and inappropriate (e.g., socioeconomic status); 5) the rate of occurrence of other important results of acute illness. Accomplishment of these goals should pave the way for more discerning use of hospital resources, and potentially could lower costs while simultaneously improving the quality of patient care. To attain these goals, the study will be restricted to patients presenting with congestive heart failure, a common problem for which physicians' decisions are quite variable and probably often sub-optimal. It will be a cohort study of 1866 patients presenting to the emergency rooms of three hospitals of different types. Data collection will include predictions by the physicians who care for these patients in the ER, and in the hospital if they are admitted; physicians' actual triage decisions, and many clinical, physician, and institutional variables. Models will be developed for each outcome using logistic regression analyses of a three-quarters random sample of the data set. Each models' performance on the remaining data will be compared to that of individual and aggregated physicians' estimates. Criteria for performance will include receiver operating characteristic curves, calibration curves, and Brier scores. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DYSFUNCTION

PREVALENCE

OF

ASYMPTOMATIC

VENTRICULAR

Principal Investigator & Institution: Rodeheffer, Richard J.; Professor; Mayo Clinic Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2001; Project Start 01-JAN-1997; Project End 31-MAR-2005 Summary: Our goals are to objectively measure cardiac function in a community cohort, to define and characterize the natural history of left ventricular dysfunction (LVD), and to develop means for early detection of LVD. LVD is hypothesized to progress from asymptomatic LVD to severe LVD, ending ultimately in disability and death. Therefore, a foundational understanding of the occurrence and natural history of ventricular function in the community is of central significance for our understanding of congestive heart failure, a major form of cardiovascular disease that is increasing in prevalence. Our first objective was to perform a cross-sectional population-based study of objectively measured ventricular function parameters and clinical disease in the community. Our study of 2050 persons > 45 yrs of age, the Prevalence of Asymptomatic Left Ventricular Dysfunction (PAVD) in Olmsted County, MN (R01 HL55502), is providing estimates of the distribution of echocardiographic ventricular systolic and diastolic function parameters in the community, and of the association between ventricular function and prevalent cardiovascular symptoms and disease. In

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collaboration with the Strong Heart Study (SHS) preliminary analysis of the PAVD and SHS cohorts has shown that both systolic and diastolic LVD are associated with elevated plasma concentrations of brain natriuretic peptide (BNP), a peptide secreted by the heart in response to increased cardiac filling pressure, that may serve as a marker to aid in the early diagnosis of LVD. Longitudinal population-based studies of ventricular function and plasma BNP, and their association with incident cardiovascular events, are not available. Having now characterized cardiac structure and function in our populationbased cross-sectional study, we propose to restudy this cohort employing the same ventricular function and BNP measurements. We will estimate the longitudinal change in ventricular structure and function and test the hypotheses that: 1) systolic/diastolic LVD are longitudinally progressive, 2) increasing plasma BNP is associated with progressive change in LV structure and function, and 3) abnormalities in LV structure, function, and BNP are associated with incident clinical events. We will thereby extend the value of this unique sentinel cohort for the population-based longitudinal study of LVD and CHF in the community. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PROGNOSTIC SIGNIFICANCE OF T WAVE ALTERNANS Principal Investigator & Institution: Bigger, J T.; Professor; Medicine; Columbia University Health Sciences New York, Ny 10032 Timing: Fiscal Year 2003; Project Start 15-SEP-2000; Project End 31-AUG-2004 Summary: (Verbatim from Applicant's Abstract): Sudden cardiac death accounts for approximately 400,000 deaths each year in the United States and remains a health problem of epidemic proportions. Most sudden cardiac deaths are caused by fatal ventricular arrhythmias. An effort aimed at the primary prevention of sudden cardiac death requires efficient identification of patients who are at high enough risk for having these arrhythmias to warrant aggressive prophylactic therapy. A number of recently completed, randomized clinical trials have demonstrated that an implantable cardiac defibrillator (ICD) can prevent sudden cardiac death in a highly selected group of highrisk patients. When these trials are viewed together, the only patients in whom the prophylactic implantation of an ICD has proven benefit are those patients identified by documented, spontaneous or inducible, sustained ventricular arrhythmias. Two randomized treatment trials (MADIT II, SCD-HEFT) are currently testing the hypothesis that implantation of an ICD will reduce mortality in patients with congestive heart failure (CHF) and left ventricular dysfunction without any further risk stratification. However, the implications of these two trials-implantation of an ICD in every patient with CHF-are unlikely to be accepted either by the medical community or by health care payers. More efficient methods of risk stratification will be necessary to identify those patients with CHF who are most likely to benefit from prophylactic treatment with an ICD. It has recently been shown that T Wave Alternans (TWA) measured during exercise is strongly associated with inducible monomorphic CVT and with subsequent spontaneous arrhythmic events. This preliminary data suggest that TWA may be an efficient and non-invasive surrogate for electrophysiologic testing to screen patients who may be at high-risk for sudden cardiac death. The purpose of this study is to evaluate the prognostic significance of TWA in a prospective epidemiologic natural history study. Ultimately, the planning of a randomized treatment trial that utilizes TWA in some combination with other risk factors to select patients at high-risk for sudden cardiac death requires answers to a number of questions from an unbiased natural history study. What is the magnitude of the increase in risk of having an arrhythmic event if TWA is present? Is the increase in risk similar for those patients with

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ischemic and non-ischemic cardiomyopathy? What is the relationship between TWA and the other risk factors (EF, NSVT, and RR variability)? Is the association between TWA and arrhythmic events independent of these other risk factors? What is the most clinically efficient method of combining risk factors to identify a group of patients at high-risk for having an arrhythmic event? The research described in this grant application will provide the data necessary to answer these questions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PROGRESSION OF HEART FAILURE Principal Investigator & Institution: Sabbah, Hani N.; Medicine; Case Western Reserve Univ-Henry Ford Hsc Research Administraion Cfp-046 Detroit, Mi 48202 Timing: Fiscal Year 2001; Project Start 01-APR-1994; Project End 31-DEC-2003 Summary: Left ventricular (LV) dysfunction, once established, worsens over time, despite the absence of intercurrent adverse events. This LV deterioration often culminates in congestive heart failure (HF). The mechanisms responsible for this process are not fully understood. We and others have speculated that progression of LV dysfunction and subsequent transition to over HF may be due, in part, to progressive global LV remodeling, and the cellular level, to ongoing loss of cardiomyocytes and/or progressive worsening of intrinsic contractile dysfunction of residual myocytes. During the past funding cycle, we showed for the first time, that progressive LV dysfunction and dilation are accompanied by ongoing loss of viable myocardium. Pioneering studies by us in dogs with HF and by others, in end-stage, explanted failed human hearts, evoked cardiomyocyte apoptosis, as a potential cause of ongoing loss of viable myocardium in HF. While critical to our knowledge of the overall pathophysiology of HF, the true importance of these findings is tempered by the existence of a major gap in our understanding of the adaptations and/or maladaptations, inherent to the HF state, that drive the process of ongoing cardiac muscle cell death that ultimately leads to intractable HF. In this application, we propose new investigations intended to close this knowledge gap. Over the next 5 years, we propose to determine if a relationship exists between 1) the severity of LV dysfunction and the extent of cardiomyocyte apoptosis; 2) progression of LV dysfunction and the activity and expression of protein phosphatases; enzymes that have been suggested to promote apoptosis and have been shown by us to be elevated in HF; and 3) the severity of LV dysfunction and susceptibility of cardiomyocytes to undergo apoptosis mediated by norepinephrine, angiotensin-II and hypoxia; all of which are classic features of HF. We further propose to examine if in-vivo treatment of HF with vascular endothelial growth factor ameliorates the hypoxic state through angiogenesis and, in doing so, prevent hypoxia-mediated apoptosis and, consequently, prevent the progression to overt HF. Finally, we will address the role of a central adaptation in HF namely, whether the process of progressive LV dilation itself promotes cardiomyocyte loss or vice versa. We will test this by surgical placement of a passive constraining device around strengths of critical findings uncovered during the previous funding cycle and are in line with our overall objective of identifying the mechanisms of progressive deterioration of LV function that is characteristic of the HF state. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: QUANTITATIVE ANALYSIS OF LEFT VENTRICULOLASTY-- CHF Principal Investigator & Institution: Ratcliffe, Mark B.; Associate Professor and Chief; Northern California Institute Res & Educ San Francisco, Ca 941211545

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Timing: Fiscal Year 2001; Project Start 17-APR-2000; Project End 31-MAR-2004 Summary: (Adapted from Applicant's Abstract): Reduction in left ventricular (LV) size (ventriculoplasty) by either LV aneurysm repair or partial ventriculectomy has been proposed as surgical treatment for congestive heart failure (CHF). Although results with both aneurysm repair and partial ventriculectomy have been mixed, a quantitative mechanical analysis of ventriculoplasty should allow the design of new surgical procedures that improve ventricular function. Changes in ventricular wall stress are believed to be stimuli for growth and remodelling. Thus, it is likely that surgical aneurysm repair is successful when it results in a reduction in wall stress, a subsequent improvement in border zone material properties and improvement in ventricular function. This proposal will build upon previous measurement of regional stress and ventricular function after aneurysm plication in the sheep aneurysm model. It will measure regional LV material properties before and after aneurysm repair with a biaxial stretching apparatus. Those ex vivo measurements will be confirmed from magnetic resonance measurements of regional cardiac deformation which in conjunction with knowledge of regional cardiac architecture and previously developed finite element techniques will be used to calculate regional in vivo cardiac material properties. With knowledge of myocardial material properties, the effect of three types of aneurysm repair, including plication, patch aneurysmorraphy, and radiofrequency (RF) infarct heating, on regional stress and global function will be calculated from finite element simulations. Model simulations will be validated by direct in vivo measurement of endsystolic and diastolic pressure-volume relationships, as well as magnetic resonance imaging (MRI) tissue tagging of regional 3-D myocardial strain components. Finally, the effect of aneurysm repair on border zone stress will be correlated with PET measurements of myocardial collagen and regional blood flow. These studies will help to identify the effect of ventriculoplasty in the failing heart. The long-term goal is to use experimental and theoretical models to design new surgical procedures for left ventriculoplasty that will improve ventricular function. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: QUANTITATIVE CARDIOLOGY

CARDIAC

PHYSIOLOGY

IN

CLINICAL

Principal Investigator & Institution: Kovacs, Sandor J.; Associate Professor; BarnesJewish Hospital Ms 90-94-212 St. Louis, Mo 63110 Timing: Fiscal Year 2001; Project Start 15-SEP-2000; Project End 31-JUL-2005 Summary: This revised application for a Midcareer Investigator Award in PatientOriented Research focuses on quantitative cardiac physiology in clinical cardiology. The goal is to mentor young investigators in multi- disciplinary clinical investigation aimed at maximizing the amount of useful information extracted. The applicant has an established record of mentoring. In 1991 he founded Washington University's Cardiovascular Biophysics Laboratory in part to serve as a training and hypothesistesting venue for patient-oriented research. Trainees will be exposed to ongoing investigations that use novel methods to explore mechanisms of human disease (congestive heart failure, systolic and diastolic dysfunction) and elucidate physiology (four-chamber heart function). Main themes of investigations include: diastolic function assessment by Doppler echocardiography via model-based image processing (MBIP); four chamber equilibrium volume determination by cardiac MRI; and hemodynamic characterization by phase-plane analysis. The intrinsically multi-disciplinary methods include clinical, cognitive, and quantitative tools for testing causal and correlative hypotheses. Trainees' support is via the Cardiovascular Division's training grant (NIH:

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5-T32-HL07081, M.E. Cain, PI). They will formulate hypotheses that require quantitative characterization of cardiac physiology via acquisition and processing of multi-channel physiological data, and test them via application of statistical methods and determination of clinical correlates. As part of the Research Plan, one completed, funded, retrospective pilot project and its natural prospective extension are described in which trainees will participate. The hypothesis project and its natural prospective extension are described in which trainees will participate. The hypothesis tested is that Doppler derived indexes of diastolic function generated by MBIP (a novel approach) are better indicators of 1-year mortality in selected elderly patients admitted to the hospital with heart failure than are conventional echocardiographic indexes (EF, deceleration time) from the same Doppler data. 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: 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.

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Congestive Heart Failure

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 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

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Project Title: REGULATION OF GENE EXPRESSION IN SKELETAL MUSCLE Principal Investigator & Institution: Kandarian, Susan C.; Professor; Health Sciences; Boston University Charles River Campus 881 Commonwealth Avenue Boston, Ma 02215 Timing: Fiscal Year 2002; Project Start 25-JUN-1992; Project End 31-MAR-2007 Summary: (provided by applicant):Skeletal muscle plasticity is characterized by dynamic functional and structural remodeling but very little is known about the regulatory mechanisms involved. The skeletal muscle sarco [or endo] plasmic reticulum calcium ATPase (SERCA1) gene is a major determinant of intracellular calcium fluxes and it is strongly transactivated by reduced contractile activity in the presence of intact innervation. The long-term goal of this project is to elucidate the molecular mechanisms of SERCA1 transactivation in muscle. The cis-regulatory and corresponding trans-acting factors will be identified which are responsible for the transactivation of SERCA1 during unloading-disuse atrophy. In vivo transcriptional activity of the SERCA1 promoter will be studied using reporter gene assays following direct muscle injection of chimeric plasmid DNA where different portions of the promoter are linked to a reporter gene. The approach will involve deletion analysis of these constructs as well as constructs

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containing mutations at specific regulatory sites, and rearrangements of proposed enhancer sequences thought to be regulating promoter activity. Gel shift assays to detect protein-DNA binding activity will be performed as well as strategies to either over express or reduce expression of putative trans-acting factors in vivo. A strength of this approach is that it will uncover molecular mechanisms involved in the transactivation of SERCA1 in the in vivo setting. A second aim will be to identify transcriptional mechanisms of SERCA1 regulation by calcium in cultured myocytes and compare this to the in vivo mechanism. The same SERCA1 promoter-reporter constructs used in vivo will transiently transfected in cultured myocytes to determine the cis-elements sensitive to calcium. Trans-acting factors will be identified using conventional strategies: proteinDNA binding assays and over expression of wild type, mutant and chimeric GAL4 transcription factors. Candidate upstream pathways will be identified via treatment of cells with specific kinase/phosphatase inhibitors in the presence of the identified calcium sensitive SERCA1 reporter. Candidate signaling proteins will be tested for involvement by over expression in the presence of the calcium sensitive SERCA1 reporter. An understanding of the regulation of SERCA1 is of fundamental importance to understanding a variety of cellular processes and disease states (e.g. congestive heart failure), and in developing pharmaceuticals for effecting improvements in muscle function due to atrophy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REMATCH TRIAL Principal Investigator & Institution: Rose, Eric A.; Professor of Surgery; Surgery; Columbia University Health Sciences New York, Ny 10032 Timing: Fiscal Year 2001; Project Start 11-APR-1997; Project End 31-AUG-2004 Summary: 600,000 Americans die each year as a result of heart disease, despite improvements in the diagnosis and treatment of cardiac problems. Recent dramatic success with heart transplantation has shown that replacement of the human heart can be achieved with remarkable prolongation of high-quality of life. Un fortunately, the limited availability of donor organs severely restricts the use of cardiac transplantation to a small minority of patients with end-stage heart failure. Recent developments in pump design and materials, however, suggest that the previously elusive goal of successful cardiac replacement with man-made pumps may soon be achieved. Experience with advanced-design wearable left ventricular assist devices used as "bridges" to transplantation has been recently extended to periods of 100 to more than 500 days. Patients can enjoy a high quality of life outside of hospital, with low fail-safe mechanisms in device design allowing expeditious and effective treatment in rare instances of mechanical device failure. In light of the ongoing high incidence and poor prognosis of end-stage heart disease and encouraging process in mechanical circulatory assistance, we propose a three-center randomized clinical trial of the wearable Thermo cardiosystems left ventricular assist device versus medical therapy of heart failure in patients who are not candidates for cardiac transplantation. Our primary hypothesis is that such devices can reduce two-year mortality by 33% (from 75% to 50%). Randomization of total of 130 patients allows an 80% power to demonstrate the anticipated survival benefit. Rigorous assessment of quality of life and the costeffectiveness of medical versus device therapy will also be conducted. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: RGS PROTEIN FUNCTION IN CARDIAC PHYSIOLOGY Principal Investigator & Institution: Muslin, Anthony J.; Barnes-Jewish Hospital Ms 9094-212 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 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

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Project Title: RISK FACTORS FOR CONGESTIVE HEART FAILURE IN WOMEN Principal Investigator & Institution: Chae, Claudia; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2001; Project Start 15-SEP-1999; Project End 31-AUG-2004 Summary: The purpose of this award is to prepare the candidate, Dr. Claudia Chae, for a career as an independent clinical scientist in cardiovascular epidemiology, with particular expertise in the prevention and treatment of congestive heart failure (CHF), her area of clinical and scientific interest. The applicant proposes a five-year program of research that prospectively examines risk factors for CHF in women, in whom limited epidemiologic data exist. The hypotheses to be examined include the influence of diabetes mellitus, obesity and abdominal adiposity, hormone replacement status, antioxidant intake and alcohol use on the risk of CHF. These studies will be performed in the Nurses' Health Study of 121,700 women currently aged 51 to 76 years. The detailed exposure information and long follow-up time in this cohort offer a unique opportunity to study, in prospective data, potentially modifiable risk factors for CHF in a very large and well-characterized population of women. At the conclusion of the award period, Dr. Chae will have acquired the advanced epidemiologic skills which will enable her to independently conduct research in the prevention and treatment of heart failure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SAFETY AND EFFICACY OF CELLULAR CARDIOMYOPLASTY Principal Investigator & Institution: Taylor, Doris A.; Associate Professor; Medicine; Duke University Durham, Nc 27706 Timing: Fiscal Year 2001; Project Start 01-AUG-1999; Project End 31-JUL-2003 Summary: Description (Adapted from Applicant's Abstract): The overall goal of this project is to determine whether autotransplantation of skeletal myoblasts into scarred or failing myocardium will lead to long term survival of the myoblast and improvement in systolic and diastolic contractile function. The Principal Investigator plans to use a model of cryoablation injury to the ventricle injecting the myoblasts into the area of damage. In the first aim she will develop a method of labeling the transplanted cells so that they could be detected late and to facilitate determination of longevity. In the second aim, she will determine regional wall motion abnormalities in the area of myoblast transplantation and determine the microenvironment to which the cells are transplanted. In the third aim, she will determine whether the viability of harvested skeletal myoblasts is altered by the presence of congestive heart failure. She will also test the efficacy of myoblast transplantation in a model of coronary ischemia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SAFETY AND EFFICACY OF EXERCISE FOR INDIVIDUALS WITH CHF Principal Investigator & Institution: Swank, Ann M.; Exercise Physiology Laboratory; University of Louisville University of Louisville Louisville, Ky 40292 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2005 Summary: (provided by applicant): Congestive heart failure is a chronic form of heart disease characterized by ventricular dysfunction and exercise intolerance. Nearly five million Americans have CHF and over 400,000 new cases are diagnosed each year. Interventions such as exercise training that have the potential to limit hospital readmissions and subsequent costly procedures will be important for cost effective disease management. The safety and effectiveness of combined strength training (ST) and aerobic exercise regimens for the individual with CHF has not been determined. Combining exercise modalities will optimize exercise outcomes. This proposal will provide preliminary data regarding the safety and effectiveness of combining strength training (ST) with aerobic exercise training for individuals with CHF. This project will use a randomized, controlled design with subjects randomly assigned to one of three experimental training groups: (1) aerobic exercise training alone (AT), (2) AT with low intensity strength training and (3) AT with high intensity strength training. Indices of ventricular function including ventricular volumes/pressures and geometry during a standardized ST exercise protocol will be measured using echocardiography to assess safety of ST. We hypothesize that adding ST to aerobic exercise will result in a similar stress to ventricular function as aerobic exercise alone indicating that combining exercise modalities may be safe for individuals with CHF. The effectiveness of adding ST to aerobic exercise will be measured through changes in muscular strength as measured by the 1-repetition maximum and quality of life changes as determined by questionnaire. Previous work from our lab indicates an average strength increase of 26 percent for a combined high intensity ST (80 percent maximal strength) and aerobic exercise program among individuals with CHF. It is hypothesized that strength gains in this investigation will be similar. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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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: 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

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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 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: SONOMICROMETRY SYSTEM FOR ROTARY BLOOD PUMP CONTROL Principal Investigator & Institution: Prem, Edward K.; Vascor, Inc. 566 Alpha Dr Pittsburgh, Pa 15238 Timing: Fiscal Year 2003; Project Start 15-JUL-2001; Project End 31-JAN-2005 Summary: (provided by applicant): Design and qualification testing of an automatic, closed-loop control system for implanted rotary blood pumps is proposed The control system is expected to significantly improve the efficacy and safety of treating Congestive Heart Failure patients with rotary blood pumps by eliminating problems associated with rotary pumps such as ventricular collapse caused by over-pumping and inadequate perfusion caused by under-pumping Three sonomicrometry transducers are permanently implanted within the wall of the left ventricle A software-based controller uses the sensed inter-transducer distances to optimally control the speed of a rotary pump to avoid excessive distension or contraction of the ventricle Specific aims of the project are to 1) Design and evaluate a clinical sonomicrometry lead suitable for human use -A formal specification will be prepared, leads and installation tools will be designed, prototypes will be fabricated, and in vitro and in vivo tests will be performed 2) Design and evaluate transducer interface circuitry capable of being sufficiently miniaturized for human implant - A formal specification will be prepared, circuitry will be designed, prototypes will be fabricated, and in vitro and in vivo tests will be performed 3) Develop and evaluate a closed loop pump control algorithm - A formal specification will be prepared, the algorithm will be developed, the algorithm will be evaluated using a computer model of the human circulatory system, and in vitro and in vivo tests will be performed 4) Fabricate and qualify sonomicrometry leads for human use - Production procedures will be prepared, a pilot production line will be setup, production processes will be validated, leads will be fabricated, and in vitro and in vivo qualification tests will be performed. 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: STICH TRIAL - NEUROHORMONAL/ CYTOKINE/ GENETIC CORE LAB Principal Investigator & Institution: Feldman, Arthur M.; Magee Professor and Chair; Medicine; Thomas Jefferson University Office of Research Administration Philadelphia, Pa 191075587 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-DEC-2006 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

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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 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: T-CELL RESPONSES PREDICT INFLUENZA RISK IN OLDER ADULTS Principal Investigator & Institution: Mcelhaney, Janet E.; Associate Professor; None; Eastern Virginia Medical School Norfolk, Va 23507 Timing: Fiscal Year 2002; Project Start 15-APR-2002; Project End 31-MAR-2005 Summary: (Provided by Applicant) This proposal addresses the NIA Program (PA-97097), "The Impact of Immune Senescence and Maturation on Vaccine Responsiveness in the Elderly" and describes a strategy to advance the basic science of influenza learned from studies in the aged mouse model which will be applied to a very high-risk population of older adults with congestive heart failure (CHF). The innovation in this proposal has been the development of a simple laboratory measure of cytotoxic Tlymphocyte (CTL) activity using an ex vivo assay of granzyme B (Grz B). This translational research will characterize the protective immunologic response to influenza vaccination, define the defective T-cell mechanism that increases risk for influenza in older adults, and determine individual risk based on clinical markers of disease severity in CHF. CHF provides a model for studying the significant added risk of serious influenza illness to that related to advancing age. In the process, important clinical indicators and laboratory measures of influenza risk will identify older people

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with a high risk for serious influenza illness. The general hypothesis is that Iow levels of Grz B predict high risk for influenza illness and are associated with a dysregulation of cytokine production in older adults. To explore this hypothesis, vaccinated healthy older adults and older adults with CHF will be studied to determine the: 1) association between antibody, cytokine and Grz B levels and the development of influenza illness, 2) mechanism underlying poor Grz B responses to influenza vaccination with advancing age and CHF, and 3) relationship between functional performance and antibody, cytokine and Grz B levels Aim (1) will be accomplished by measuring antibody, cytokine and Grz B levels before and after influenza vaccination in different risk groups for influenza. From these results, the principal investigator will test a threshold level of Grz B for its ability to predict risk for influenza-related illness in older people with CHF. The components of a "protective" T-cell response to vaccination will be defined. Aim (2) will be accomplished by measuring age and CHF-related changes in cytokine and Grz B levels and the number virus-specific T-cells in different T-cell subsets. Aim (3) will be accomplished by comparing cytokine and Grz B levels in virus-stimulated PBMC, to clinical indicators of CHF severity as a potential marker of "immunologic frailty" for complications of influenza. By comparing these immune responses to influenza vaccination in healthy young and older adults and older adults with CHF, the mechanism that leads to decreased efficacy of current influenza vaccines will be identified. The goal is to define an immunologic test that measures influenza risk, a measure critical to future vaccine development and targeted prophylaxis in older adults. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

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. 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

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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: THYROID HORMONE RECEPTOR FUNCTION IN CARDIAC HYPERTROPHY Principal Investigator & Institution: Ojamaa, Kaie M.; Associate Professor; North ShoreLong Island Jewish Res Inst Jewish Research Institute Manhasset, Ny 11030 Timing: Fiscal Year 2003; Project Start 28-APR-2003; Project End 31-MAR-2007 Summary: (provided by applicant): Many aspects of cardiac contractile function are determined by the action of thyroid hormones, specifically triiodothyronine (T3), on myocyte-specific gene transcription that is mediated byT3 binding to one or more nuclear thyroid hormone receptors (TR). The precise role of the individual TRs (TR alpha I,TR beta 1) and their post-transcriptional modification in determining transcription of specific cardiomyocyte genes, including co-myosin heavy chain (alphaMHC), remains unknown. The myocardium in conditions of pathologic and physiologic hypertrophy exhibits altered expression of many T3-responsive genes, which can be partially normalized by T3 treatment. The present application will test the hypothesis that impaired T3 responsiveness in the hypertrophied heart is the result of altered expression and phosphorylation of TR isoforms which affect all aspects of nuclear receptor function including DNA binding, dimerization, interaction with co-regulators, ligand affinity and transcriptional activity. In the first two specific aims, we propose to test the hypothesis that the hypertrophic cardiac phenotype is a result of changes in nuclear, content of TR isoforms and that the individual TR alpha I and beta 1 isoforms are differentially phosphorylated as assessed by isolation of nuclear proteins from purified adult rat ventricular myocytes. Our preliminary data suggest that the non-T3 binding isoform, TR alpha 2,has the unique ability to repress T3-inducible transcription of cardiac alpha-MHC and SERCA2 genes. A recombinant adenovirus strategy will be used in specific aim 3 to overexpress TR alpha 2 protein in cultured cardiomyocytes,and the resulting changes in transcription of the endogenous alpha-MHC gene will be measured by a novel assay to quantify alpha-MHC heteronuclear RNA. Specific aim 4 will test will the hypothesis that protein kinase C signaling pathways that are activated in the hypertrophic myocardium result in phosphorylation of specific TR isoforms, which in turn mediate changes in cardiac phenotype remarkably similar to that of the hypothyroid heart. We will study the effects of adenoviral-mediated overexpression of individual PKC delta, epsilon, and zeta isoenzymes on specific TR isoform phosphorylation and alpha-MHC gene transcription. Completion of these studies will provide novel mechanistic information regarding the role of TRs in mediating the hypertrophic phenotype, and provide the rationale for the potential therapeutic utility of T3 in the setting of congestive heart failure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: TIME SERIES MODELING OF TRENDS IN MEDICATION PRESCRIBING Principal Investigator & Institution: Stafford, Randall S.; Assistant Professor; Medicine; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2002; Project Start 19-APR-2002; Project End 31-DEC-2004 Summary: Physician decisions regarding medication prescribing have a large impact on health care costs and clinical outcomes. Surprisingly little is known, however, about the

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relative impact of a range of factors that may influence physician behavior in the prescribing of medications. By extension, the ability to explain and project trends in medication prescribing is currently limited. This study will develop a novel economic model of the simultaneous influence of multiple determinants on trends in medication prescribing. Econometric time-series regression techniques will be used to estimate the relative influence of temporally varying predictor variables and discrete temporal events on observed national trends in the prescribing of pharmaceuticals for hypertension, depression, asthma, and congestive heart failure. Nationally representative quarterly data on 1978 through 2000 trends in drug prescribing for these conditions will come from the National Disease and Therapeutic Index survey available through IMS Health. Quarterly patient sample sizes in 1998 are about 1,700 for depression, 550 for congestive heart failure, 5,100 for hypertension and 2,000 for asthma. Data on potential predictors of trends will be developed from a variety of sources. Drug-specific trend information on pharmaceutical promotion and wholesale drug prices also will be available from IMS Health. Other predictors will include information on drug dosing, other drug characteristics, clinical trial results publication, media reporting on medications, and clinical guideline publication. By constructing a comprehensive model of the temporal determinants of prescribing behavior, this study will assess the relative influence of these factors. Econometric time series regression models built on the theory of demand for differentiated products will be employed to test specific hypotheses regarding the role of these factors. A key hypothesis will be that promotional influences are more potent than scientific influences. In addition, the research will evaluate hypotheses related to the influence of drug prices, the interaction of science and promotion, and the impact of brand name expiration. Results from the analysis will be relevant to efforts to design and implement clinical and health policies to encourage the effective and cost-effective use of medications. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

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) 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

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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: VENTRICULAR DYNAMICS FROM SURGICALLY INSERTED MARKERS Principal Investigator & Institution: Miller, D Craig.; Professor; Cardiothoracic Surgery; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2003; Project Start 01-FEB-1983; Project End 31-JUL-2008 Summary: The studies outlined in this application employ radiopaque marker technology in ovine experimental models to test hypotheses concerning the mechanisms for left ventricular (LV) remodeling leading to congestive heart failure (CHF) and/or chronic ischemic mitral regurgitation (CIMR). In addition to standard LV and valvular marker arrays, we have added LV transmural beadsets for simultaneous measurement of 4-D biomechanics of myofiber sheets and extracellular matrix. These studies focus on LV systolic torsion, LV diastolic torsional recoil, and transmural LV normal strains and shear strains. The knowledge derived should lead to improved surgical and medical therapies based on rational criteria for the lethal cascade culminating in CHF after a myocardial infarction (MI). We have recently discovered that LV torsion recoil, crucial to rapid early diastolic LV filling, is globally abolished by an MI causing CIMR, yet

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systolic torsion is preserved in all but the infarcted region. Elimination of LV torsion recoil may be an important initial CHF trigger in CIMR. To provide a mechanistic understanding of this phenomenon, we have developed a new and powerful technological capability (analysis of 3-D motion of transmural beadsets) which allows detailed examination of transmural LV normal strains and shear strains; these data can be transformed, using quantitative histologic information, to measure myofiber dynamics throughout the wall, throughout the entire cardiac cycle, and throughout the entire post-MI period of LV remodeling. We will test four global hypotheses: 1.) CIMR arises as a LV disease process whereby an inferior MI produces transmural strain abnormalities in the myofibers in remote, normally-perfused LV regions, which triggers a deleterious cascade that ultimately creates additional wall strain abnormalities in the remote viable regions; 2.) The CIMR disease process begins primarily as a diastolic mechanism involving limitation of normal fiber and chamber recoil mechanisms required to augment LV compliance rapidly in earliest diastole, thereby facilitating active LV filling at a low left atrial pressures; 3.) The MR observed in CIMR only reflects the severity of the underlying LV systolic dysfunction (reflecting LV dilatation and distortion of the valvular-ventricular apparatus sufficient to produce leaflet malcoaptation), and is not the central mechanism leading to CHF; and, 4.) Restriction of post-infarct mitral annular and LV dilatation favorably affects this remodeling cascade, as well as prevents CIMR. Testing these hypotheses will be possible using the unique capabilities of our measurement technology to track specific transmural LV wall, ventricular, annular, and leaflet anatomical sites on a beat-to-beat basis whenever desired as the LV remodeling process evolves over time. The knowledge gained should translate directly into more rational surgical as well as medical treatments for patients after an MI with CHF, CIMR, or both. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: VENTRICULAR MATRIX REMODELING: CORRELATES AND PROGNOSIS Principal Investigator & Institution: Ramachandran, Vasan S.; Associate Professor of Medicine; Medicine; Boston University Medical Campus 715 Albany St, 560 Boston, Ma 02118 Timing: Fiscal Year 2001; Project Start 01-JUN-2001; Project End 31-MAY-2005 Summary: Recent studies have established that cardiac extracellular matrix (ECM) remodeling is a major determinant of pathologic LV hypertrophy (LVH) and progressive LV dilatation, and as a result, contributes to the development of LV dysfunction and overt congestive heart failure (CHF). The recent development of reliable serologic assays for procollagen peptides, metalloproteinases (MMP) and their tissue inhibitors (TIMP), and cytokines permits the in vivo assessment of LV ECM remodeling, and raises the possibility of expanding the utility of these markers 'from the bench to the bedside.' Prior studies of ECM biomarkers in CHF have been limited to cross-sectional investigations of small samples of highly selected patients with advanced disease. The fundamental question whether serum markers of ECM remodeling are important correlates of LV dilatation or LVH, or are independent predictors of incident CHF in the community remains unanswered. We propose to assess the diagnostic and prognostic value of serum markers of LV remodeling (ECM markers: procollagen peptides, MMP-9, TIMP-1; and aldosterone, TNF-alpha) in a stratified sample of 1244 subjects from the community-based Framingham Study. The aims of this proposal are to: 1. Determine the relations between serum markers of ECM remodeling and traditional CHF risk factors. 2. Analyze the cross-sectional relations between markers of

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ECM remodeling and : echocardiographic LVH and LV dilatation; Doppler indices of LV filling; serum natriuretic peptides. 3. Investigate prospectively the relations between ECM remodeling markers and: progressive LV dilatation and LVH, and CHF incidence, adjusting for standard risk factors. We hypothesize that biomarkers of ECM remodeling will permit us to identify individuals with LVH and LV dilatation, and will improve our ability to predict CHF risk beyond that already achievable through use of known risk factors. The Framingham Study is uniquely suited for this research by virtue of the single-site, population-based design, availability of antecedent and contemporary risk factor data, use of standardized criteria for CHF, and the continuous longitudinal surveillance of all study subjects. The proposed translational research will likely yield seminal information that could directly improve our efforts to prevent CHF through the biochemical assessment of cardiac ECM remodeling. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: VIDEOPHONE MONITORING OF HEART FAILURE SYMPTOM PATTERNS Principal Investigator & Institution: Patterson, Patricia K.; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2001; Project Start 15-SEP-2001; Project End 31-AUG-2004 Summary: (from applicant's Abstract) The proposed pilot test will explore the feasibility of identifying symptom patterns in older persons with advanced congestive heart failure by videophone rather than in-person home visits. The aims are to: a) identify symptom patterns of frequency, severity and duration; b) determine whether remote visual and audio communication is more advantageous than audio alone for monitoring severe CHF, according to patients and nurses; c) determine the frequency with which clinical measurements are advised and/or obtained and d) identify relationships among symptom patterns and subject characteristics of health status, clinical status, functional status, quality of life and retrospective and prospective health utilization, A prospective longitudinal non-experimental design is planned with 15 outpatients who will receive 10 weekly videophone calls from an advanced practice nurse for observations and data collection regarding CHF symptoms. A subset of 20 calls will be recorded with audio and audiovisual methods, and four nurses will observe the recordings and rate them for ease of assessing patients. A comparison of communication receptivity between sound and sound-plus-image among skilled cardiac nurses will provide cutting edge knowledge on which to build telehealth care delivery models. Additional analyses will characterize the sample, identify symptom characteristics, symptom patterns and perceptions of videophone utility. The data will be used to develop analysis models of symptom patterns over time in individuals and aggregates. This work will contribute new knowledge about symptoms in a traditionally high-cost chronically ill population that has not been widely studied for symptom patterns or telenursing applications. 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

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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 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

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Affymetrix microarrays to determine genes associated with hypertrophy in failing explanted human myocardium. Multiple analytic approaches will be used, including a hypothesis-based analysis of pre-selected candidate genes, exploratory analyses, and global analyses of patterns in gene expression. In Aim 2, the applicant will demonstrate that myocardial XO activity correlates with expression of these hypertrophy genes in humans. In Aim 3, the applicant will test the hypothesis that XO inhibition with allopurinol attenuates the expression of hypertrophy genes in serial endomyocardial biopsies, and prevents an increase in cardiac mass in patients with dilated cardiomyopathy. These experiments will determine the transcriptional targets of XO in human myocardium, thereby clarifying the role of oxidative stress in heart failure. Moreover. they are the first steps in determining whether XO inhibition is a novel treatment strategy for heart failure. This research will be performed at the Johns Hopkins Medical Institutions under the mentorship of Dr. Joshua Hare, an expert in the field of oxidative stress in heart failure. Genomic analyses will be performed in collaboration with the HopGene PGAmApplied Genomics in Cardiopulmonary Disease. The applicant's interdisciplinary training, strong mentorship, career development program, supportive environment, and novel research plan will give him the experience and tools he needs to develop into a highly successful, independent clinical investigator. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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

Beta-blockers in severe congestive heart failure. by Farquhar D.; 2001 Aug 7; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=81349

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Changing trends in mortality and admissions to hospital for elderly patients with congestive heart failure in Montreal. by Feldman DE, Thivierge C, Guerard L, Dery V, Kapetanakis C, Lavoie G, Beck EJ.; 2001 Oct 16; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=81537

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Clinical treatment reverses attentional deficits in congestive heart failure. by Almeida OP, Tamai S.; 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=57979

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

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

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Congestive heart failure in rats is associated with increased expression and targeting of aquaporin-2 water channel in collecting duct. by Nielsen S, Terris J, Andersen D, Ecelbarger C, Frokiaer J, Jonassen T, Marples D, Knepper MA, Petersen JS.; 1997 May 13; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=24699

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Congestive heart failure: What can we offer our patients? by Kostuk WJ.; 2001 Oct 16; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=81540

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Management of congestive heart failure: a gender gap may still exist. Observations from a contemporary cohort. by Burstein JM, Yan R, Weller I, Abramson BL.; 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=149453

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Management of congestive heart failure: How well are we doing? by Giannetti N.; 2001 Aug 7; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=81332

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Myocyte proliferation in end-stage cardiac failure in humans. by Kajstura J, Leri A, Finato N, Di Loreto C, Beltrami CA, Anversa P.; 1998 Jul 21; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=21157

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Pacing in congestive heart failure. by Morris-Thurgood JA, Frenneaux MP.; 2000; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=59611

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Quality of congestive heart failure treatment at a Canadian teaching hospital. by Weil E, Tu JV.; 2001 Aug 7; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=81327

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Transcatheter Coil Occlusion of a Thoracic Arteriovenous Fistula in an Infant with Congestive Heart Failure. by Recto MR, Elbl F.; 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101150

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

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

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•

A clinical pathway for congestive heart failure. Author(s): Hoskins LM, Clark HM, Schroeder MA, Walton-Moss B, Thiel L. Source: Home Healthcare Nurse. 2001 April; 19(4): 207-17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11985252&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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Acute and 3-month treatment effects of candesartan cilexetil on hemodynamics, neurohormones, and clinical symptoms in patients with congestive heart failure. Author(s): Mitrovic V, Willenbrock R, Miric M, Seferovic P, Spinar J, Dabrowski M, Kiowski W, Marks DS, Alegria E, Dukat A, Lenz K, Arens HA. Source: American Heart Journal. 2003 March; 145(3): E14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12660683&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 congestive heart failure after laparoscopic cholecystectomy: a case report. Author(s): Giaquinto D, Swigar K, Johnson MD. Source: Aana Journal. 2003 February; 71(1): 17-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12776645&dopt=Abstract

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Addition of valsartan to an angiotensin-converting enzyme inhibitor improves cardiac sympathetic nerve activity and left ventricular function in patients with congestive heart failure. Author(s): Kasama S, Toyama T, Kumakura H, Takayama Y, Ichikawa S, Suzuki T, Kurabayashi M. Source: Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine. 2003 June; 44(6): 884-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12791814&dopt=Abstract

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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): 71-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12723015&dopt=Abstract

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Age and sex do not bias the use of angiotensin-converting enzyme inhibitors in acute myocardial infarction and congestive heart failure. Author(s): Blackman IC, Bond M, Bowling A, Banning A, Dudley N, Elder A, Martin A, Rai GS. Source: Journal of the American Geriatrics Society. 2003 April; 51(4): 572-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12657085&dopt=Abstract

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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): Silverberg DS, Wexler D, Blum M, Sheps D, Schwartz D, Yachnin T, Baruch R, Tchebiner J, Zubkov A, Shaked M, Steinbruch S, Keren G, Iaina A. Source: Perit Dial Int. 2001; 21 Suppl 3: S236-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11887828&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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Alcohol consumption and risk for congestive heart failure in the Framingham Heart Study. Author(s): Walsh CR, Larson MG, Evans JC, Djousse L, Ellison RC, Vasan RS, Levy D. Source: Annals of Internal Medicine. 2002 February 5; 136(3): 181-91. Summary for Patients In: http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11827493&dopt=Abstract

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Aldosterone as a target in congestive heart failure. Author(s): Rajagopalan S, Pitt B. Source: The Medical Clinics of North America. 2003 March; 87(2): 441-57. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12693733&dopt=Abstract

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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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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: congestive heart failure and beyond. Author(s): Lombardi WL, Litwin SE. Source: Coronary Artery Disease. 1999 September; 10(6): 361-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10474785&dopt=Abstract

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Apnea-hypopnea threshold for CO2 in patients with congestive heart failure. Author(s): Xie A, Skatrud JB, Puleo DS, Rahko PS, Dempsey JA. Source: American Journal of Respiratory and Critical Care Medicine. 2002 May 1; 165(9): 1245-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11991873&dopt=Abstract

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Apnea-related heart rate variability in congestive heart failure patients. Author(s): Tateishi O, Shouda T, Sakai T, Honda Y, Mochizuki S, Machida K. Source: Clinical and Experimental Hypertension (New York, N.Y. : 1993). 2003 April; 25(3): 183-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12716080&dopt=Abstract

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Assessing elderly patients with congestive heart failure via in-home interactive telecommunication. Author(s): Jenkins RL, McSweeney M. Source: Journal of Gerontological Nursing. 2001 January; 27(1): 21-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11915093&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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Beneficial neurohormonal profile of spironolactone in severe congestive heart failure: results from the RALES neurohormonal substudy. Author(s): Rousseau MF, Gurne O, Duprez D, Van Mieghem W, Robert A, Ahn S, Galanti L, Ketelslegers JM; Belgian RALES Investigators. Source: Journal of the American College of Cardiology. 2002 November 6; 40(9): 1596601. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12427411&dopt=Abstract

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Benefit and safety of enhanced external counterpulsation in treating coronary artery disease patients with a history of congestive heart failure. Author(s): Lawson WE, Kennard ED, Holubkov R, Kelsey SF, Strobeck JE, Soran O, Feldman AM; IEPR investigators. Source: Cardiology. 2001; 96(2): 78-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11740136&dopt=Abstract

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Beta-adrenergic blockers in chronic congestive heart failure. Author(s): Gattis WA. Source: American Journal of Health-System Pharmacy : Ajhp : Official Journal of the American Society of Health-System Pharmacists. 2002 March 1; 59(5): 467-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11887416&dopt=Abstract

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Beta-blockade in hypertension and congestive heart failure. Author(s): Ambrosioni E, Bacchelli S, Esposti DD, Borghi C. Source: Journal of Cardiovascular Pharmacology. 2001 December; 38 Suppl 3: S25-31. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11811389&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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BiPAP in severe acute congestive heart failure. Author(s): Krall S. Source: The Journal of Emergency Medicine. 2002 October; 23(3): 301. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12426022&dopt=Abstract

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Bisoprolol dose-response relationship in patients with congestive heart failure: a subgroup analysis in the cardiac insufficiency bisoprolol study(CIBIS II). Author(s): Simon T, Mary-Krause M, Funck-Brentano C, Lechat P, Jaillon P. Source: European Heart Journal. 2003 March; 24(6): 552-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12643888&dopt=Abstract

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Biventricular pacing for congestive heart failure. Author(s): Lagrotteria JM. Source: Critical Care Nursing Quarterly. 2003 January-March; 26(1): 50-8; Quiz 59-60. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12669948&dopt=Abstract

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Biventricular pacing for congestive heart failure: early experience in surgical epicardial versus coronary sinus lead placement. Author(s): Izutani H, Quan KJ, Biblo LA, Gill IS. Source: Heart Surg Forum. 2002; 6(1): E1-6; Discussion E1-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12611737&dopt=Abstract

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Biventricular pacing for patients with severe congestive heart failure: a single center experience. Author(s): Mascioli G, Curnis A, Bontempi L, Dei Cas L. Source: Ital Heart J. 2002 October; 3(10): 598-602. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12478818&dopt=Abstract

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Biventricular pacing in a patient with severe congestive heart failure. Author(s): Tanaka H, Okishige K, Murakami M, Someya T, Arai H, Sunamori M. Source: Jpn J Thorac Cardiovasc Surg. 2002 July; 50(7): 290-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12166268&dopt=Abstract

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Biventricular pacing in congestive heart failure: a boost toward finer living. Author(s): Luck JC, Wolbrette DL, Boehmer JP, Ulsh PJ, Silber D, Naccarelli GV. Source: Current Opinion in Cardiology. 2002 January; 17(1): 96-101. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11790940&dopt=Abstract

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Blunted sympathetic response in diabetic patients with decompensated congestive heart failure. Author(s): Burger AJ, Aronson D. Source: International Journal of Cardiology. 2001 December; 81(2-3): 243-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11744142&dopt=Abstract

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BNP and congestive heart failure. Author(s): Cowie MR, Mendez GF. Source: Progress in Cardiovascular Diseases. 2002 January-February; 44(4): 293-321. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12007084&dopt=Abstract

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B-type natriuretic peptide (BNP): can it improve our management of patients with congestive heart failure? Author(s): Mueller C, Buser P. Source: Swiss Medical Weekly : Official Journal of the Swiss Society of Infectious Diseases, the Swiss Society of Internal Medicine, the Swiss Society of Pneumology. 2002 December 14; 132(43-44): 618-22. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12587045&dopt=Abstract

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B-type natriuretic peptide for diagnosis and treatment of congestive heart failure. Author(s): Kuster GM, Tanner H, Printzen G, Suter TM, Mohacsi P, Hess OM. Source: Swiss Medical Weekly : Official Journal of the Swiss Society of Infectious Diseases, the Swiss Society of Internal Medicine, the Swiss Society of Pneumology. 2002 December 14; 132(43-44): 623-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12587046&dopt=Abstract

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B-type natriuretic peptide for the treatment of congestive heart failure. Author(s): Schreiner GF, Protter AA. Source: Current Opinion in Pharmacology. 2002 April; 2(2): 142-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11950624&dopt=Abstract

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B-type natriuretic peptide levels: diagnostic and prognostic in congestive heart failure: what's next? Author(s): Maisel A. Source: Circulation. 2002 May 21; 105(20): 2328-31. Erratum In: Circulation 2002 July 16; 106(3): 387. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12021215&dopt=Abstract

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B-type natriuretic peptide measurements in diagnosing congestive heart failure in the dyspneic emergency department patient. Author(s): Maisel A. Source: Reviews in Cardiovascular Medicine. 2002; 3 Suppl 4: S10-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12439426&dopt=Abstract

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Cardiac energetics in congestive heart failure. Author(s): Ashrafian H. Source: Circulation. 2002 February 12; 105(6): E44-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11839640&dopt=Abstract

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Cardiac resynchronization in patients with congestive heart failure and chronic atrial fibrillation: effect of upgrading to biventricular pacing after chronic right ventricular pacing. Author(s): Leon AR, Greenberg JM, Kanuru N, Baker CM, Mera FV, Smith AL, Langberg JJ, DeLurgio DB. Source: Journal of the American College of Cardiology. 2002 April 17; 39(8): 1258-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11955841&dopt=Abstract

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Care management interventions for older patients with congestive heart failure. Author(s): Windham BG, Bennett RG, Gottlieb S. Source: Am J Manag Care. 2003 June; 9(6): 447-59; Quiz 460-1. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12816174&dopt=Abstract

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Characterization of transient outward K+ current and ultra-rapid delayed rectifier K+ current in isolated human atrial myocytes from patients with congestive heart failure. Author(s): Xu ZX, Jin MW. Source: Acta Pharmacologica Sinica. 2002 February; 23(2): 110-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11866869&dopt=Abstract

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Comparative haemodynamic responses to the first dose of short- and long-acting ACE inhibitors in patients with congestive heart failure. Author(s): Anthopoulos L, Apostolou T, Bonoris P, Foussas S, Lefkos N, Zombolos S. Source: Current Medical Research and Opinion. 2001; 17(4): 290-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11922403&dopt=Abstract

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Comparison of candesartan, enalapril, and their combination in congestive heart failure: randomized evaluation of strategies for left ventricular dysfunction (RESOLVD) pilot study. The RESOLVD Pilot Study Investigators. Author(s): McKelvie RS, Yusuf S, Pericak D, Avezum A, Burns RJ, Probstfield J, Tsuyuki RT, White M, Rouleau J, Latini R, Maggioni A, Young J, Pogue J. Source: Circulation. 1999 September 7; 100(10): 1056-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10477530&dopt=Abstract

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Comparison of incidences of congestive heart failure in older African-Americans, Hispanics, and whites. Author(s): Aronow WS, Ahn C, Kronzon I. Source: The American Journal of Cardiology. 1999 September 1; 84(5): 611-2, A9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10482169&dopt=Abstract

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Congestive heart failure and continuous positive airway pressure therapy: support of a new modality for improving the prognosis and survival of patients with advanced congestive heart failure. Author(s): Midelton GT, Frishman WH, Passo SS. Source: Heart Disease. 2002 March-April; 4(2): 102-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11975841&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 in renal transplant recipients: risk factors, outcomes, and relationship with ischemic heart disease. Author(s): Rigatto C, Parfrey P, Foley R, Negrijn C, Tribula C, Jeffery J. Source: Journal of the American Society of Nephrology : Jasn. 2002 April; 13(4): 1084-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11912270&dopt=Abstract

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Congestive heart failure. Author(s): Alt M. Source: Nebr Nurse. 2002 March-May; 35(1): 19-20; Quiz 21, 38. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11951358&dopt=Abstract

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Congestive heart failure: a house divided. Author(s): Weber KT. Source: Congestive Heart Failure (Greenwich, Conn.). 2002 January-February; 8(1): 8-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11821622&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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Congestive heart failure: improving outcomes for at-risk populations. Author(s): Oduwole AM. Source: Ethn Dis. 2002 Winter; 12(1): S2-46-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11913642&dopt=Abstract

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Congestive heart failure: understanding the pathophysiology and management. Author(s): Fletcher L, Thomas D. Source: Journal of the American Academy of Nurse Practitioners. 2001 June; 13(6): 24957. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11930867&dopt=Abstract

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Co-prescribing of medications used to treat obstructive lung disease, congestive heart failure and depression among users of topical beta blockers: estimates from three US Veterans Affairs Medical Centers. Author(s): Valuck RJ, Perlman JI, Anderson C, Wortman GI. Source: Pharmacoepidemiology and Drug Safety. 2001 October-November; 10(6): 511-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11828833&dopt=Abstract

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Correlation of the Agency for Health Care Policy and Research congestive heart failure admission guideline with mortality: peer review organization voluntary hospital association initiative to decrease events (PROVIDE) for congestive heart failure. Author(s): Graff L, Orledge J, Radford MJ, Wang Y, Petrillo M, Maag R. Source: Annals of Emergency Medicine. 1999 October; 34(4 Pt 1): 429-37. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10499942&dopt=Abstract

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Couples coping with congestive heart failure: role and gender differences in psychological distress. Author(s): Rohrbaugh MJ, Cranford JA, Shoham V, Nicklas JM, Sonnega JS, Coyne JC. Source: Journal of Family Psychology : Jfp : Journal of the Division of Family Psychology of the American Psychological Association (Division 43). 2002 March; 16(1): 3-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11915408&dopt=Abstract

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Decreased serum vascular endothelial growth factor concentrations in patients with congestive heart failure. Author(s): Arakawa H, Ikeda U, Hojo Y, Ueno S, Nonaka-Sarukawa M, Yamamoto K, Shimada K. Source: Heart (British Cardiac Society). 2003 February; 89(2): 207-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12527680&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 congestive heart failure in type 2 diabetic patients with microalbuminuria or proteinuria: observations from the DIABHYCAR (type 2 DIABetes, Hypertension, CArdiovascular Events and Ramipril) study. Author(s): Vaur L, Gueret P, Lievre M, Chabaud S, Passa P; DIABHYCAR Study Group (type 2 DIABetes, Hypertension, CARdiovascular Events and Ramipril) study. Source: Diabetes Care. 2003 March; 26(3): 855-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12610049&dopt=Abstract

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Diaphragmatic function after intense exercise in congestive heart failure patients. Author(s): Kufel TJ, Pineda LA, Junega RG, Hathwar R, Mador MJ. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 2002 December; 20(6): 1399-405. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12503695&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 sodium intake and incidence of congestive heart failure in overweight US men and women: first National Health and Nutrition Examination Survey Epidemiologic Follow-up Study. Author(s): He J, Ogden LG, Bazzano LA, Vupputuri S, Loria C, Whelton PK. Source: Archives of Internal Medicine. 2002 July 22; 162(14): 1619-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12123406&dopt=Abstract

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Digitalis for treatment of congestive heart failure in patients in sinus rhythm. Author(s): Hood WB Jr, Dans A, Guyatt GH, Jaeschke R, McMurray J. Source: Nurs Times. 2001 August 23-29; 97(34): 40. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11957658&dopt=Abstract

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Digitalis for treatment of congestive heart failure in patients in sinus rhythm. Author(s): Hood WB, Dans A, Guyatt GH, Jaeschke R, McMurray JV. Source: Cochrane Database Syst Rev. 2001; (3): Cd002901. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11687032&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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Dilated cardiomyopathies as a cause of congestive heart failure. Author(s): Maisch B, Ristic AD, Hufnagel G, Funck R, Alter P, Tontsch D, Pankuweit S. Source: Herz. 2002 March; 27(2): 113-34. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12025458&dopt=Abstract

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Dissociation between hemodynamic changes and symptom improvement in patients with advanced congestive heart failure. Author(s): Shah MR, Hasselblad V, Stinnett SS, Kramer JM, Grossman S, Gheorghiade M, Adams KF Jr, Swedberg K, Califf RM, O'Connor CM. Source: European Journal of Heart Failure : Journal of the Working Group on Heart Failure of the European Society of Cardiology. 2002 June; 4(3): 297-304. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12034155&dopt=Abstract

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Diuretic therapy and resistance in congestive heart failure. Author(s): Ellison DH. Source: Cardiology. 2001; 96(3-4): 132-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11805380&dopt=Abstract

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Diuretics in the treatment of patients who present congestive heart failure and hypertension. Author(s): Reyes AJ. Source: Journal of Human Hypertension. 2002 March; 16 Suppl 1: S104-13. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11986906&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 a low-salt diet reduce morbidity and mortality in congestive heart failure? Author(s): Meadows R, Johnson ED. Source: The Journal of Family Practice. 2002 July; 51(7): 615. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12160497&dopt=Abstract

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Dofetilide in patients with congestive heart failure and left ventricular dysfunction. Danish Investigations of Arrhythmia and Mortality on Dofetilide Study Group. Author(s): Torp-Pedersen C, Moller M, Bloch-Thomsen PE, Kober L, Sandoe E, Egstrup K, Agner E, Carlsen J, Videbaek J, Marchant B, Camm AJ. Source: The New England Journal of Medicine. 1999 September 16; 341(12): 857-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10486417&dopt=Abstract

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Doxazosin and congestive heart failure. Author(s): Sica DA. Source: Congestive Heart Failure (Greenwich, Conn.). 2002 May-June; 8(3): 178-84. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12045387&dopt=Abstract

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Doxazosin and congestive heart failure. Author(s): Messerli FH. Source: Journal of the American College of Cardiology. 2001 November 1; 38(5): 1295-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11691497&dopt=Abstract

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Doxorubicin cardiotoxicity: prevention of congestive heart failure with serial cardiac function monitoring with equilibrium radionuclide angiocardiography in the current era. Author(s): Mitani I, Jain D, Joska TM, Burtness B, Zaret BL. Source: Journal of Nuclear Cardiology : Official Publication of the American Society of Nuclear Cardiology. 2003 March-April; 10(2): 132-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12673177&dopt=Abstract

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Drug absorption in congestive heart failure: impact on management. Author(s): Sica DA. Source: Progress in Cardiovascular Nursing. 1999 Spring; 14(2): 72-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10457961&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 diltiazem on cardiac function assessed by echocardiography and neurohumoral factors after reperfused myocardial infarction without congestive heart failure. Author(s): Maki N, Yoshiyama M, Omura T, Yoshimura T, Kawarabayashi T, Sakamoto K, Hirota K, Iida H, Takeuchi K, Yoshikawa J. Source: Cardiovascular Drugs and Therapy / Sponsored by the International Society of Cardiovascular Pharmacotherapy. 2001 November; 15(6): 493-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11916358&dopt=Abstract

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Effect of dofetilide on QT dispersion and the prognostic implications of changes in QT dispersion for patients with congestive heart failure. Author(s): Brendorp B, Elming H, Jun L, Kober L, Torp-Pedersen C; DIAMOND Study Group. Danish Investigations Of Arrhythmia and Mortality On Dofetilide. Source: European Journal of Heart Failure : Journal of the Working Group on Heart Failure of the European Society of Cardiology. 2002 March; 4(2): 201-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11959050&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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Effect of vasoactive therapy on heart rate variability in patients with acutely decompensated congestive heart failure. Author(s): Burger AJ, Aronson D. Source: The American Journal of Cardiology. 1999 August 15; 84(4): 476-8, A10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10468094&dopt=Abstract

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Effect of verapamil in elderly patients with left ventricular diastolic dysfunction as a cause of congestive heart failure. Author(s): Hung MJ, Cherng WJ, Kuo LT, Wang CH. Source: Int J Clin Pract. 2002 January-February; 56(1): 57-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11831838&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 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 exercise training on peak performance and quality of life in congestive heart failure patients. Author(s): Gottlieb SS, Fisher ML, Freudenberger R, Robinson S, Zietowski G, Alves L, Krichten C, Vaitkevicus P, McCarter R. Source: Journal of Cardiac Failure. 1999 September; 5(3): 188-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10496191&dopt=Abstract

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Effects of the 1994 Canadian Cardiovascular Society clinical practice guidelines for congestive heart failure. Author(s): Tsuyuki RT, Ackman ML, Montague TJ; Clinical Quality Improvement Network Investigators. Source: The Canadian Journal of Cardiology. 2002 February; 18(2): 147-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11875584&dopt=Abstract

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Efficacy and safety of berberine for congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. Author(s): Zeng XH, Zeng XJ, Li YY. Source: The American Journal of Cardiology. 2003 July 15; 92(2): 173-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12860219&dopt=Abstract

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Efficacy 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 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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Electrical therapy in patients with congestive heart failure introduction. Author(s): Blanck Z, Georgakopoulos ND, Berger M, Cooley R, Dhala A, Sra J, Deshpande S, Akhtar M. Source: Current Problems in Cardiology. 2002 February; 27(2): 45-93. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11893983&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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Evaluation of arteriolar hyalinosis of the skin of patients with chronic congestive heart failure. Author(s): Kishimoto C, Shioji K, Ito H, Kinoshita M, Lee JD, Shimizu H, Ueda T. Source: Circulation Journal : Official Journal of the Japanese Circulation Society. 2002 April; 66(4): 382-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11954954&dopt=Abstract

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Evaluation of pulmonary arterial catheter parameters utilizing intermittent pneumatic compression boots in congestive heart failure. Author(s): Ringley CD, Johanning JM, Gruenberg JC, Veverka TJ, Barber KR. Source: The American Surgeon. 2002 March; 68(3): 286-9; Discussion 289-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11893109&dopt=Abstract

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Evidence-based emergency medicine. Predicting the future: can this patient with acute congestive heart failure be safely discharged from the emergency department? Author(s): Ann Intern Med. 2002 Feb 5;136(3):I16 Source: Annals of Emergency Medicine. 2002 February; 39(2): 181-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11928738

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Exercise as a treatment modality for congestive heart failure. Author(s): Monchamp T, Frishman WH. Source: Heart Disease. 2002 March-April; 4(2): 110-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11975842&dopt=Abstract

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Factors precipitating congestive heart failure--role of patient non-compliance. Author(s): Joshi PP, Mohanan CJ, Sengupta SP, Salkar RG. Source: J Assoc Physicians India. 1999 March; 47(3): 294-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10999123&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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Female patients with congestive heart failure: how they conceive their life situation. Author(s): Martensson J, Karlsson JE, Fridlund B. Source: Journal of Advanced Nursing. 1998 December; 28(6): 1216-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9888366&dopt=Abstract

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Fetal congestive heart failure: correlation of Tei-index and Cardiovascular-score. Author(s): Falkensammer CB, Paul J, Huhta JC. Source: Journal of Perinatal Medicine. 2001; 29(5): 390-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11723840&dopt=Abstract

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Fifteen years of ACE-inhibition in congestive heart failure. Author(s): Rapezzi C. Source: Ital Heart J. 2000 September; 1 Suppl 3: S10-1. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11003010&dopt=Abstract

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Firing properties of single muscle vasoconstrictor neurons in the sympathoexcitation associated with congestive heart failure. Author(s): Macefield VG, Rundqvist B, Sverrisdottir YB, Wallin BG, Elam M. Source: Circulation. 1999 October 19; 100(16): 1708-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10525490&dopt=Abstract

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First clinical trial with etomoxir in patients with chronic congestive heart failure. Author(s): Schmidt-Schweda S, Holubarsch C. Source: Clinical Science (London, England : 1979). 2000 July; 99(1): 27-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10887055&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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Fostering hope in the elderly congestive heart failure patient in critical care. Author(s): Roberts SL, Johnson LH, Keely B. Source: Geriatric Nursing (New York, N.Y.). 1999 July-August; 20(4): 195-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10711090&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 of congestive heart failure in older persons with prior myocardial infarction and serum low-density lipoprotein cholesterol > or = 125 mg/dl treated with statins versus no lipid-lowering drug. Author(s): Aronow WS, Ahn C. Source: The American Journal of Cardiology. 2002 July 15; 90(2): 147-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12106845&dopt=Abstract

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From digoxin to angiotensin-converting enzyme inhibitors: issues in pharmacotherapy for congestive heart failure. Author(s): Hackenbruck HA. Source: Clin Excell Nurse Pract. 2000 July; 4(4): 197-204. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11261079&dopt=Abstract

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Frontiers in congestive heart failure: anemia is associated with worse symptoms, greater impairment in functional capacity, and a significant increase in mortality in patients with advanced heart failure. Author(s): Tepper D. Source: Congestive Heart Failure (Greenwich, Conn.). 2002 July-August; 8(4): 235-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12147949&dopt=Abstract

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Frontiers in congestive heart failure: heart failure in a cold climate. Seasonal variation in heart failure-related morbidity and mortality. Author(s): Tepper D. Source: Congestive Heart Failure (Greenwich, Conn.). 2002 March-April; 8(2): 90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11927783&dopt=Abstract

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Frontiers in congestive heart failure: initial experience with an implantable cardioverter-defibrillator incorporating cardiac resynchronization therapy. Author(s): Tepper D. Source: Congestive Heart Failure (Greenwich, Conn.). 2002 March-April; 8(2): 91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11927784&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 capacity in patients with congestive heart failure. Author(s): Hendrican MC, McKelvie RS, Smith T, McCartney N, Pogue J, Teo KK, Yusuf S. Source: Journal of Cardiac Failure. 2000 September; 6(3): 214-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10997747&dopt=Abstract

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Functional decline after congestive heart failure and acute myocardial infarction and the impact of psychological attributes. A prospective study. Author(s): Kempen GI, Sanderman R, Miedema I, Meyboom-de Jong B, Ormel J. Source: Quality of Life Research : an International Journal of Quality of Life Aspects of Treatment, Care and Rehabilitation. 2000; 9(4): 439-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11131936&dopt=Abstract

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Functional status and depression among men and women with congestive heart failure. Author(s): Murberg TA, Bru E, Aarsland T, Svebak S. Source: International Journal of Psychiatry in Medicine. 1998; 28(3): 273-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9844832&dopt=Abstract

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Gas exchange efficiency in congestive heart failure II. Author(s): Johnson RL Jr. Source: Circulation. 2001 February 20; 103(7): 916-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11181463&dopt=Abstract

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Gas exchange efficiency in congestive heart failure. Author(s): Johnson RL Jr. Source: Circulation. 2000 June 20; 101(24): 2774-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10859280&dopt=Abstract

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Gender differences in 1-year survival and quality of life among patients admitted with congestive heart failure. Author(s): Chin MH, Goldman L. Source: Medical Care. 1998 July; 36(7): 1033-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9674621&dopt=Abstract

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Gender-related differences in modulation of heart rate in patients with congestive heart failure. Author(s): Aronson D, Burger AJ. Source: Journal of Cardiovascular Electrophysiology. 2000 October; 11(10): 1071-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11059968&dopt=Abstract

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Generalist and cardiologist care for congestive heart failure. Author(s): Srivatsa S, Amjadi HR. Source: Annals of Internal Medicine. 2000 September 19; 133(6): 481-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10975971&dopt=Abstract

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Generalist and cardiologist care for congestive heart failure. Author(s): Nurhussein MA. Source: Annals of Internal Medicine. 2000 September 19; 133(6): 481; Author Reply 482. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10975970&dopt=Abstract

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Generic versus disease-specific health status measures. An example using coronary artery disease and congestive heart failure patients. Author(s): Wolinsky FD, Wyrwich KW, Nienaber NA, Tierney WM. Source: Evaluation & the Health Professions. 1998 June; 21(2): 216-43. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10183345&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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Glucose and insulin abnormalities relate to functional capacity in patients with congestive heart failure. Author(s): Suskin N, McKelvie RS, Burns RJ, Latini R, Pericak D, Probstfield J, Rouleau JL, Sigouin C, Solymoss CB, Tsuyuki R, White M, Yusuf S. Source: European Heart Journal. 2000 August; 21(16): 1368-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10952826&dopt=Abstract

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Grading the graders of congestive heart failure in children. Author(s): Ross RD. Source: The Journal of Pediatrics. 2001 May; 138(5): 618-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11343033&dopt=Abstract

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Growth hormone as a potential future therapy for congestive heart failure. Author(s): Fazio S, Cittadini A, Biondi B, Palmieri EA, Sacca L. Source: Coronary Artery Disease. 1999 September; 10(6): 383-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10474788&dopt=Abstract

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Growth hormone as additional treatment for patients with chronic congestive heart failure: a review. Author(s): Bergh CH. Source: Growth Hormone & Igf Research : Official Journal of the Growth Hormone Research Society and the International Igf Research Society. 1998 April; 8 Suppl B: 171-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10990157&dopt=Abstract

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Growth hormone therapy in patients with congestive heart failure: need for further research. Author(s): Johnson MR, Gheorghiade M. Source: American Heart Journal. 1999 June; 137(6): 989-91. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10347317&dopt=Abstract

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Guidelines clarify drug therapy for congestive heart failure. Author(s): Rollins G. Source: Rep Med Guidel Outcomes Res. 2001 March 8; 12(5): 7-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12053921&dopt=Abstract

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Health related quality of life in patients with congestive heart failure: comparison with other chronic diseases and relation to functional variables. Author(s): Juenger J, Schellberg D, Kraemer S, Haunstetter A, Zugck C, Herzog W, Haass M. Source: Heart (British Cardiac Society). 2002 March; 87(3): 235-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11847161&dopt=Abstract

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Heart rate variability enhances the prognostic value of established parameters in patients with congestive heart failure. Author(s): Kruger C, Lahm T, Zugck C, Kell R, Schellberg D, Schweizer MW, Kubler W, Haass M. Source: Zeitschrift Fur Kardiologie. 2002 December; 91(12): 1003-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12490990&dopt=Abstract

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Heart rate variability in congestive heart failure. Author(s): Tateishi O, Shouda T, Azuma Y, Chin K, Nogimura T, Gotou Y, Itou T, Mochizuki S, Machida K. Source: Clinical and Experimental Hypertension (New York, N.Y. : 1993). 2002 JanuaryFebruary; 24(1-2): 75-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11848171&dopt=Abstract

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Heart rate variability measurement correlates with cardiac norepinephrine spillover in congestive heart failure. Author(s): Tygesen H, Rundqvist B, Waagstein F, Wennerblom B. Source: The American Journal of Cardiology. 2001 June 1; 87(11): 1308-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11377364&dopt=Abstract

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Hibernation and congestive heart failure. Author(s): Dutka DP, Camici PG. Source: Heart Failure Reviews. 2003 April; 8(2): 167-73. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12766496&dopt=Abstract

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High prevalence of left ventricular systolic and diastolic asynchrony in patients with congestive heart failure and normal QRS duration. Author(s): Yu CM, Lin H, Zhang Q, Sanderson JE. Source: Heart (British Cardiac Society). 2003 January; 89(1): 54-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12482792&dopt=Abstract

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Home care nursing for persons with congestive heart failure: description and relationship to hospital readmission. Author(s): Martens KH. Source: Home Healthcare Nurse. 2000 June; 18(6): 404-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11951301&dopt=Abstract

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Home-based intervention in congestive heart failure: long-term implications on readmission and survival. Author(s): Stewart S, Horowitz JD. Source: Circulation. 2002 June 18; 105(24): 2861-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12070114&dopt=Abstract

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Hormonal profile in patients with congestive heart failure. Author(s): Kontoleon PE, Anastasiou-Nana MI, Papapetrou PD, Alexopoulos G, Ktenas V, Rapti AC, Tsagalou EP, Nanas JN. Source: International Journal of Cardiology. 2003 February; 87(2-3): 179-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12559538&dopt=Abstract

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Hormone levels predict congestive heart failure, mortality. Author(s): SoRelle R. Source: Circulation. 2002 February 12; 105(6): E9073-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11842833&dopt=Abstract

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Hormone replacement therapy and the risk of incident congestive heart failure: the Cardiovascular Health Study. Author(s): Rea TD, Psaty BM, Heckbert SR, Cushman M, Meilahn E, Olson JL, Lemaitre RN, Smith NL, Sotoodehnia N, Chaves PH. Source: Journal of Women's Health (2002). 2003 May; 12(4): 341-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12804341&dopt=Abstract

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Hospital outcomes in patients presenting with congestive heart failure complicating acute myocardial infarction: a report from the Second National Registry of Myocardial Infarction (NRMI-2). Author(s): Wu AH, Parsons L, Every NR, Bates ER; Second National Registry of Myocardial Infarction. Source: Journal of the American College of Cardiology. 2002 October 16; 40(8): 1389-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12392826&dopt=Abstract

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Hospitalization for congestive heart failure: is it still a cardiology business? Author(s): Grigioni F, Carinci V, Favero L, Bacchi Reggiani L, Magnani G, Potena L, Barbieri A, Magelli C, Branzi A, Magnani B. Source: European Journal of Heart Failure : Journal of the Working Group on Heart Failure of the European Society of Cardiology. 2002 January; 4(1): 99-104. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11812670&dopt=Abstract

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Hospitalized congestive heart failure after renal transplantation in the United States. Author(s): Abbott KC, Hypolite IO, Hshieh P, Cruess D, Taylor AJ, Agodoa LY. Source: Annals of Epidemiology. 2002 February; 12(2): 115-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11880219&dopt=Abstract

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How do beta-blockers improve ventricular function in patients with congestive heart failure? Author(s): Barry WH, Gilbert EM. Source: Circulation. 2003 May 20; 107(19): 2395-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12756189&dopt=Abstract

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Hyperkalemia in congestive heart failure patients aged 63 to 85 years with subclinical renal disease. Author(s): Obialo CI, Ofili EO, Mirza T. Source: The American Journal of Cardiology. 2002 September 15; 90(6): 663-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12231103&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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Hyperthyroidism: a “curable” cause of congestive heart failure--three case reports and a review of the literature. Author(s): Riaz K, Forker AD, Isley WL, Hamburg MS, McCullough PA. Source: Congestive Heart Failure (Greenwich, Conn.). 2003 January-February; 9(1): 40-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12556677&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 and concurrent acid-base and electrolyte abnormalities in patients with congestive heart failure. Author(s): Milionis HJ, Alexandrides GE, Liberopoulos EN, Bairaktari ET, Goudevenos J, Elisaf MS. Source: European Journal of Heart Failure : Journal of the Working Group on Heart Failure of the European Society of Cardiology. 2002 March; 4(2): 167-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11959045&dopt=Abstract

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Identifying opportunities to address the congestive heart failure burden: the Improving Cardiovascular Outcomes in Nova Scotia (ICONS) study. Author(s): Howlett JG, Johnstone DE, Sketris I, O'Reilly M, Horne GS, Cox JL; Improving Cardiovascular Outcomes in Nova Scotia investigators. Source: The Canadian Journal of Cardiology. 2003 March 31; 19(4): 439-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12704493&dopt=Abstract

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Immunomodulating therapy: new treatment modality in congestive heart failure. Author(s): Aukrust P, Damas JK, Gullestad L. Source: Congestive Heart Failure (Greenwich, Conn.). 2003 March-April; 9(2): 64-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12671336&dopt=Abstract

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Impact of beta-blocker treatment on the prognostic value of currently used risk predictors in congestive heart failure. Author(s): Zugck C, Haunstetter A, Kruger C, Kell R, Schellberg D, Kubler W, Haass M. Source: Journal of the American College of Cardiology. 2002 May 15; 39(10): 1615-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12020488&dopt=Abstract

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Impact of congestive heart failure and other cardiac diseases on patient outcomes. Author(s): Collins AJ. Source: Kidney International. Supplement. 2002 October; (81): S3-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12230476&dopt=Abstract

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Impact of pharmacotherapy on lymphocyte volumes and activity of the Na+/H+ exchanger in patients with congestive heart failure. Author(s): Feuring M, Jester I, Tillmann HC, Bertsch T, Kugler I, Schmidt BM, Wehling M. Source: Methods Find Exp Clin Pharmacol. 2001 September; 23(7): 409-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11771856&dopt=Abstract

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Improvement of cardiac function after treatment with octreotide followed by transsphenoidal surgery in an acromegalic patient who presented with congestive heart failure. Author(s): Shimakura A, Miyakoshi H, Ohkuwa H, Kitabayashi M, Komai T, Hisada A, Aoki K, Sakagami S, Kobayashi K, Takata S. Source: Japanese Heart Journal. 2002 January; 43(1): 69-77. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12041892&dopt=Abstract

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Increased circulating interleukin-18 in patients with congestive heart failure. Author(s): Naito Y, Tsujino T, Fujioka Y, Ohyanagi M, Okamura H, Iwasaki T. Source: Heart (British Cardiac Society). 2002 September; 88(3): 296-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12181230&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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Induction of functional inducible nitric oxide synthase in monocytes of patients with congestive heart failure. Link with tumour necrosis factor-alpha. Author(s): Comini L, Bachetti T, Agnoletti L, Gaia G, Curello S, Milanesi B, Volterrani M, Parrinello G, Ceconi C, Giordano A, Corti A, Ferrari R. Source: European Heart Journal. 1999 October; 20(20): 1503-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10493849&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-mediated glucose uptake in congestive heart failure. Author(s): Doehner W, Anker SD. Source: The American Journal of Cardiology. 1999 September 15; 84(6): 761-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10498157&dopt=Abstract

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Intact negative feedback of four cardiac hormones in congestive heart failure. Author(s): Vesely DL, San Miguel GI, Hassan I, Schocken DD. Source: Metabolism: Clinical and Experimental. 2002 May; 51(5): 582-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11979389&dopt=Abstract

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Interleukin-18 in patients with congestive heart failure: induction of atrial natriuretic peptide gene expression. Author(s): Seta Y, Kanda T, Tanaka T, Arai M, Sekiguchi K, Yokoyama T, Kurimoto M, Tamura J, Kurabayashi M. Source: Res Commun Mol Pathol Pharmacol. 2000 July-August; 108(1-2): 87-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11758978&dopt=Abstract

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Internet and telephone-based congestive heart failure program as effective as and cheaper than traditional one, study says. Author(s): Jackson RA. Source: Rep Med Guidel Outcomes Res. 2001 February 22; 12(4): 9-10, 12. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11767797&dopt=Abstract

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Intravenous milrinone in treatment of advanced congestive heart failure. Author(s): Zewail AM, Nawar M, Vrtovec B, Eastwood C, Kar MN, Delgado RM 3rd. Source: Texas Heart Institute Journal / from the Texas Heart Institute of St. Luke's Episcopal Hospital, Texas Children's Hospital. 2003; 30(2): 109-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12809251&dopt=Abstract

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Intravenous nesiritide (human B-type natriuretic peptide) reduces plasma endothelin1 levels in patients with decompensated congestive heart failure. Author(s): Aronson D, Burger AJ. Source: The American Journal of Cardiology. 2002 August 15; 90(4): 435-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12161240&dopt=Abstract

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Intravenous nesiritide vs nitroglycerin for treatment of decompensated congestive heart failure: a randomized controlled trial. Author(s): Publication Committee for the VMAC Investigators (Vasodilatation in the Management of Acute CHF). Source: Jama : the Journal of the American Medical Association. 2002 March 27; 287(12): 1531-40. Erratum In: Jama 2002 August 7; 288(5): 577. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11911755&dopt=Abstract

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Intravenous vasodilator therapy in congestive heart failure. Author(s): Moazemi K, Chana JS, Willard AM, Kocheril AG. Source: Drugs & Aging. 2003; 20(7): 485-508. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12749747&dopt=Abstract

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Is specialty care associated with improved survival of patients with congestive heart failure? Author(s): Indridason OS, Coffman CJ, Oddone EZ. Source: American Heart Journal. 2003 February; 145(2): 300-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12595848&dopt=Abstract

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Is there a role for thiamine in the management of congestive heart failure? Author(s): Saif MW. Source: Southern Medical Journal. 2003 January; 96(1): 114-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12602748&dopt=Abstract

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Large left-to-right shunts and congestive heart failure increase total energy expenditure in infants with ventricular septal defect. Author(s): Farrell AG, Schamberger MS, Olson IL, Leitch CA. Source: The American Journal of Cardiology. 2001 May 1; 87(9): 1128-31, A10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11348620&dopt=Abstract

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Lean tissue adjusted peak oxygen consumption in congestive heart failure. Author(s): Wensel R, Anker SD. Source: Journal of the American College of Cardiology. 2001 July; 38(1): 287-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11451290&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 bundle-branch block is associated with increased 1-year sudden and total mortality rate in 5517 outpatients with congestive heart failure: a report from the Italian network on congestive heart failure. Author(s): Baldasseroni S, Opasich C, Gorini M, Lucci D, Marchionni N, Marini M, Campana C, Perini G, Deorsola A, Masotti G, Tavazzi L, Maggioni AP; Italian Network on Congestive Heart Failure Investigators. Source: American Heart Journal. 2002 March; 143(3): 398-405. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11868043&dopt=Abstract

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Left ventricular and biventricular pacing in congestive heart failure. Author(s): Gerber TC, Nishimura RA, Holmes DR Jr, Lloyd MA, Zehr KJ, Tajik AJ, Hayes DL. Source: Mayo Clinic Proceedings. 2001 August; 76(8): 803-12. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11499820&dopt=Abstract

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Left ventricular volume reduction by radiofrequency heating of chronic myocardial infarction in patients with congestive heart failure. Author(s): Victal OA, Teerlink JR, Gaxiola E, Wallace AW, Najar S, Camacho DH, Gutierrez A, Herrera G, Zuniga G, Mercado-Rios F, Ratcliffe MB. Source: Circulation. 2002 March 19; 105(11): 1317-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11901042&dopt=Abstract

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Level of activities associated with mobility during everyday life in patients with chronic congestive heart failure as measured with an “activity monitor”. Author(s): van den Bergemons H, Bussmann J, Balk A, Keijzer-Oster D, Stam H. Source: Physical Therapy. 2001 September; 81(9): 1502-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11688587&dopt=Abstract

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Life-sustaining treatments in patients who died of chronic congestive heart failure compared with metastatic cancer. Author(s): Tanvetyanon T, Leighton JC. Source: Critical Care Medicine. 2003 January; 31(1): 60-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12544994&dopt=Abstract

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Lifetime risk for developing congestive heart failure: the Framingham Heart Study. Author(s): Lloyd-Jones DM, Larson MG, Leip EP, Beiser A, D'Agostino RB, Kannel WB, Murabito JM, Vasan RS, Benjamin EJ, Levy D; Framingham Heart Study. Source: Circulation. 2002 December 10; 106(24): 3068-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12473553&dopt=Abstract

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Limitation of excessive extracellular matrix turnover may contribute to survival benefit of spironolactone therapy in patients with congestive heart failure: insights from the randomized aldactone evaluation study (RALES). Rales Investigators. Author(s): Zannad F, Alla F, Dousset B, Perez A, Pitt B. Source: Circulation. 2000 November 28; 102(22): 2700-6. Erratum In: Circulation 2001 January 23; 103(3): 476. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11094035&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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Loculated pericardial effusion due to congestive heart failure: an unusual case of vanishing tumor--a case report. Author(s): Sakamoto H, Sakamaki T, Kanda T, Kurabayashi M, Nagai R, Fujii J. Source: Angiology. 1999 August; 50(8): 683-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10451237&dopt=Abstract

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Long-acting natriuretic peptide, vessel dilator, and kaliuretic peptide enhance urinary excretion rate of albumin, total protein, and beta(2)-microglobulin in patients with congestive heart failure. Author(s): Vesely DL, Perez-Lamboy GI, Schocken DD. Source: Journal of Cardiac Failure. 2001 March; 7(1): 55-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11264551&dopt=Abstract

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Longstanding atrial fibrillation causes depletion of atrial natriuretic peptide in patients with advanced congestive heart failure. Author(s): van den Berg MP, Tjeerdsma G, Jan de Kam P, Boomsma F, Crijns HJ, van Veldhuisen DJ. Source: European Journal of Heart Failure : Journal of the Working Group on Heart Failure of the European Society of Cardiology. 2002 June; 4(3): 255-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12034149&dopt=Abstract

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Long-term benefits of biventricular pacing in congestive heart failure: results from the MUltisite STimulation in cardiomyopathy (MUSTIC) study. Author(s): Linde C, Leclercq C, Rex S, Garrigue S, Lavergne T, Cazeau S, McKenna W, Fitzgerald M, Deharo JC, Alonso C, Walker S, Braunschweig F, Bailleul C, Daubert JC. Source: Journal of the American College of Cardiology. 2002 July 3; 40(1): 111-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12103264&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 intermittent dobutamine infusion combined with oral amiodarone improves the survival of patients with severe congestive heart failure. Author(s): Nanas JN, Kontoyannis DA, Alexopoulos GP, Anastasiou-Nana MI, Tsagalou EP, Stamatelopoulos SF, Moulopoulos SD. Source: Chest. 2001 April; 119(4): 1173-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11296186&dopt=Abstract

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Long-term left ventricular pacing: assessment and comparison with biventricular pacing in patients with severe congestive heart failure. Author(s): Touiza A, Etienne Y, Gilard M, Fatemi M, Mansourati J, Blanc JJ. Source: Journal of the American College of Cardiology. 2001 December; 38(7): 1966-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11738301&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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Low vitamin D status: a contributing factor in the pathogenesis of congestive heart failure? Author(s): Zittermann A, Schleithoff SS, Tenderich G, Berthold HK, Korfer R, Stehle P. Source: Journal of the American College of Cardiology. 2003 January 1; 41(1): 105-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12570952&dopt=Abstract

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Mammalian cardenolides as biomarkers in congestive heart failure. Author(s): Jortani SA, Valdes R Jr. Source: Cardiovascular Toxicology. 2001; 1(2): 165-70. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12213990&dopt=Abstract

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Management of new-onset congestive heart failure in a patient with complex congenital heart disease. Author(s): Khan AN, Boatman J, Anderson AS. Source: Congestive Heart Failure (Greenwich, Conn.). 2002 January-February; 8(1): 54-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11821629&dopt=Abstract

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Management of the dental patient with congestive heart failure. Author(s): Rhodus NL, Falace DA. Source: Gen Dent. 2002 May-June; 50(3): 260-5, Quiz 266-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12116514&dopt=Abstract

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Marinobufagenin, an endogenous ligand of alpha-1 sodium pump, is a marker of congestive heart failure severity. Author(s): Fridman AI, Matveev SA, Agalakova NI, Fedorova OV, Lakatta EG, Bagrov AY. Source: Journal of Hypertension. 2002 June; 20(6): 1189-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12023690&dopt=Abstract

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Mechanisms and management of diuretic resistance in congestive heart failure. Author(s): De Bruyne LK. Source: Postgraduate Medical Journal. 2003 May; 79(931): 268-71. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12782772&dopt=Abstract

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Medical resource use and costs of congestive heart failure after carvedilol use. Author(s): Najib MM, Goldberg Arnold RJ, Kaniecki DJ, Pettit KG, Roth D, Antell L, Xuan J. Source: Heart Disease. 2002 March-April; 4(2): 70-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11975837&dopt=Abstract

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Metastatic malignant melanoma presenting as congestive heart failure: diagnosis by transoesophageal echocardiography. Author(s): Schneider B, Zienkiewicz T. Source: European Journal of Echocardiography : the Journal of the Working Group on Echocardiography of the European Society of Cardiology. 2002 June; 3(2): 168-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12114103&dopt=Abstract

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Mortality associated with the quality of care of patients hospitalized with congestive heart failure. Author(s): Luthi JC, McClellan WM, Fitzgerald D, Krumholz HM, Delaney RJ, Bratzler DW, Elward K, Cangialos CB, Ballar DJ; Multi-State Collaborative Congestive Heart Failure Study Group. Source: International Journal for Quality in Health Care : Journal of the International Society for Quality in Health Care / Isqua. 2002 February; 14(1): 15-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11871625&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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Myocardial imaging with 123I-BMIPP in patients with congestive heart failure. Author(s): Ishida Y, Yasumura Y, Nagaya N, Fukuchi K, Komamura K, Takamiya M, Miyatake K. Source: International Journal of Cardiac Imaging. 1999 February; 15(1): 71-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10453405&dopt=Abstract

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Myocardial Na,K-ATPase: the molecular basis for the hemodynamic effect of digoxin therapy in congestive heart failure. Author(s): Kjeldsen K, Norgaard A, Gheorghiade M. Source: Cardiovascular Research. 2002 September; 55(4): 710-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12176120&dopt=Abstract

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Nesiritide (Natrecor): a new treatment for acutely decompensated congestive heart failure. Author(s): Colbert K, Greene MH. Source: Critical Care Nursing Quarterly. 2003 January-March; 26(1): 40-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12669946&dopt=Abstract

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Neurohumoral activation and ventricular arrhythmias in patients with decompensated congestive heart failure: role of endothelin. Author(s): Aronson D, Burger AJ. Source: Pacing and Clinical Electrophysiology : Pace. 2003 March; 26(3): 703-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12698670&dopt=Abstract

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New rapid laboratory test for congestive heart failure B-type natriuretic peptide (BNP). Author(s): Barlow JF. Source: S D J Med. 2002 November; 55(11): 467. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12449586&dopt=Abstract

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New therapeutic choices in the management of acute congestive heart failure. Author(s): Young JB. Source: Reviews in Cardiovascular Medicine. 2001; 2 Suppl 2: S19-24. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12439358&dopt=Abstract

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New therapeutic options in congestive heart failure: Part I. Author(s): McMurray J, Pfeffer MA. Source: Circulation. 2002 April 30; 105(17): 2099-106. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11980691&dopt=Abstract

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New therapeutic options in congestive heart failure: Part II. Author(s): McMurray J, Pfeffer MA. Source: Circulation. 2002 May 7; 105(18): 2223-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11994259&dopt=Abstract

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New therapies for the treatment of congestive heart failure. Author(s): Burger AJ, Burger MR, Aronson D. Source: Drugs Today (Barc). 2002 January; 38(1): 31-48. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12532183&dopt=Abstract

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NO balance: regulation of the cytoskeleton in congestive heart failure by nitric oxide. Author(s): Badorff C, Dimmeler S. Source: Circulation. 2003 March 18; 107(10): 1348-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12642351&dopt=Abstract

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Noninvasive assessment of cardiac resynchronization therapy for congestive heart failure using myocardial strain and left ventricular peak power as parameters of myocardial synchrony and function. Author(s): Popovic ZB, Grimm RA, Perlic G, Chinchoy E, Geraci M, Sun JP, Donal E, Xu XF, Greenberg NL, Wilkoff BL, Thomas JD. Source: Journal of Cardiovascular Electrophysiology. 2002 December; 13(12): 1203-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12521333&dopt=Abstract

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Nontransplant surgical options for congestive heart failure. Author(s): Kherani AR, Garrido MJ, Cheema FH, Naka Y, Oz MC. Source: Congestive Heart Failure (Greenwich, Conn.). 2003 January-February; 9(1): 1724. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12556673&dopt=Abstract

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Observations from a home-based congestive heart failure intervention. Author(s): Ohldin A. Source: Home Care Provider. 2001 December; 6(6): 212-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11744898&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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One in 5 at risk for congestive heart failure. Author(s): SoRelle R. Source: Circulation. 2002 December 10; 106(24): E9066-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12473571&dopt=Abstract

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Optimization of atrioventricular delay and follow-up in a patient with congestive heart failure and with bi-ventricular pacing. Author(s): Ishikawa T, Sumita S, Kimura K, Kikuchi M, Matsushita K, Ohkusu Y, Nakagawa T, Kosuge M, Usui T, Umemura A. Source: Japanese Heart Journal. 2001 November; 42(6): 781-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11933927&dopt=Abstract

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Optimizing treatment for chronic congestive heart failure in children. Author(s): Shaddy RE. Source: Critical Care Medicine. 2001 October; 29(10 Suppl): S237-40. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11593067&dopt=Abstract

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Orthostatic hypotension in elderly women with congestive heart failure. Author(s): Potocka-Plazak K, Plazak W. Source: Aging (Milano). 2001 October; 13(5): 378-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11820711&dopt=Abstract

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Oscillations in peripheral arterial tone in congestive heart failure patients: a new marker for Cheyne-Stokes breathing. Author(s): Freimark D, Adler Y, Sheffy J, Schechter D, Schwammenthal E, Wiser I, Motro M, Lavie P. Source: Cardiology. 2002; 98(1-2): 21-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12373043&dopt=Abstract

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Outcome of congestive heart failure in elderly persons: influence of left ventricular systolic function. The Cardiovascular Health Study. Author(s): Gottdiener JS, McClelland RL, Marshall R, Shemanski L, Furberg CD, Kitzman DW, Cushman M, Polak J, Gardin JM, Gersh BJ, Aurigemma GP, Manolio TA. Source: Annals of Internal Medicine. 2002 October 15; 137(8): 631-9. Summary for Patients In: http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12379062&dopt=Abstract

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Overview: old and new controversies in the treatment of advanced congestive heart failure. Author(s): Loh E. Source: Journal of Cardiac Failure. 2001 June; 7(2 Suppl 1): 1-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11605163&dopt=Abstract

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Oxygen desaturation and heart rate variability due to Cheyne-Stokes respiration in congestive heart failure patients. Author(s): Tateishi O, Mochizuki S, Machida K. Source: Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie. 2002; 56 Suppl 2: 345S-348S. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12653191&dopt=Abstract

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Patient perceptions of quality of life and treatment in an outpatient congestive heart failure clinic. Author(s): Paul S, Sneed N. Source: Congestive Heart Failure (Greenwich, Conn.). 2002 March-April; 8(2): 74-6, 77-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11927780&dopt=Abstract

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Percentage of peak-to-peak pulsatility of portal blood flow can predict right-sided congestive heart failure. Author(s): Hu JT, Yang SS, Lai YC, Shih CY, Chang CW. Source: World Journal of Gastroenterology : Wjg. 2003 August; 9(8): 1828-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12918130&dopt=Abstract

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Pharmacotherapy in congestive heart failure: diuretic resistance and strategies to overcome resistance in patients with congestive heart failure. Author(s): Ravnan SL, Ravnan MC, Deedwania PC. Source: Congestive Heart Failure (Greenwich, Conn.). 2002 March-April; 8(2): 80-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11927781&dopt=Abstract

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Plasma lipophilic antioxidants and malondialdehyde in congestive heart failure patients: relationship to disease severity. Author(s): Polidori MC, Savino K, Alunni G, Freddio M, Senin U, Sies H, Stahl W, Mecocci P. Source: Free Radical Biology & Medicine. 2002 January 15; 32(2): 148-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11796203&dopt=Abstract

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Plasma oxidized low-density lipoprotein as a prognostic predictor in patients with chronic congestive heart failure. Author(s): Tsutsui T, Tsutamoto T, Wada A, Maeda K, Mabuchi N, Hayashi M, Ohnishi M, Kinoshita M. Source: Journal of the American College of Cardiology. 2002 March 20; 39(6): 957-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11897436&dopt=Abstract

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Prevalence of depression in congestive heart failure. Author(s): Havranek EP, Ware MG, Lowes BD. Source: The American Journal of Cardiology. 1999 August 1; 84(3): 348-50, A9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10496452&dopt=Abstract

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Prognostic impact of workload in patients with congestive heart failure. Author(s): Huelsmann M, Stefenelli T, Berger R, Frey B, Pacher R. Source: American Heart Journal. 2002 February; 143(2): 308-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11835036&dopt=Abstract

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Prognostic judgments and triage decisions for patients with acute congestive heart failure. Author(s): Smith WR, Poses RM, McClish DK, Huber EC, Clemo FL, Alexander D, Schmitt BP. Source: Chest. 2002 May; 121(5): 1610-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12006451&dopt=Abstract

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Prolonged oxygen uptake kinetics during low-intensity exercise are related to poor prognosis in patients with mild-to-moderate congestive heart failure. Author(s): Schalcher C, Rickli H, Brehm M, Weilenmann D, Oechslin E, Kiowski W, Brunner-La Rocca HP. Source: Chest. 2003 August; 124(2): 580-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12907546&dopt=Abstract

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Pulmonary function, cardiac function, and exercise capacity in a follow-up of patients with congestive heart failure treated with carvedilol. Author(s): Guazzi M, Agostoni P, Matturri M, Pontone G, Guazzi MD. Source: American Heart Journal. 1999 September; 138(3 Pt 1): 460-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10467196&dopt=Abstract

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QRS duration and mortality in patients with congestive heart failure. Author(s): Iuliano S, Fisher SG, Karasik PE, Fletcher RD, Singh SN; Department of Veterans Affairs Survival Trial of Antiarrhythmic Therapy in Congestive Heart Failure. Source: American Heart Journal. 2002 June; 143(6): 1085-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12075267&dopt=Abstract

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Qt dispersion has no prognostic information for patients with advanced congestive heart failure and reduced left ventricular systolic function. Author(s): Brendorp B, Elming H, Jun L, Kober L, Malik M, Jensen GB, Torp-Pedersen C. Source: Circulation. 2001 February 13; 103(6): 831-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11171791&dopt=Abstract

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QT interval dispersion as a predictor of arrhythmic events in congestive heart failure. Importance of aetiology. Author(s): Galinier M, Vialette JC, Fourcade J, Cabrol P, Dongay B, Massabuau P, Boveda S, Doazan JP, Fauvel JM, Bounhoure JP. Source: European Heart Journal. 1998 July; 19(7): 1054-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9717041&dopt=Abstract

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Qtc interval as a guide to select those patients with congestive heart failure and reduced left ventricular systolic function who will benefit from antiarrhythmic treatment with dofetilide. Author(s): Brendorp B, Elming H, Jun L, Kober L, Malik M, Jensen GB, Torp-Pedersen C; DIAMOND Study Group. Source: Circulation. 2001 March 13; 103(10): 1422-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11245647&dopt=Abstract

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Quality of care and hospital readmission in congestive heart failure: an explicit review process. Author(s): Polanczyk CA, Newton C, Dec GW, Di Salvo TG. Source: Journal of Cardiac Failure. 2001 December; 7(4): 289-98. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11782850&dopt=Abstract

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Quality of care by race and gender for congestive heart failure and pneumonia. Author(s): Ayanian JZ, Weissman JS, Chasan-Taber S, Epstein AM. Source: Medical Care. 1999 December; 37(12): 1260-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10599607&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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Quality of congestive heart failure treatment at a Canadian teaching hospital. Author(s): Weil E, Tu JV. Source: Cmaj : Canadian Medical Association Journal = Journal De L'association Medicale Canadienne. 2001 August 7; 165(3): 284-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11517643&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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Quinapril in patients with congestive heart failure: controlled trial versus captopril. Author(s): Acanfora D, Furgi G, Trojano L, Picone C, Iannuzzi GL, Rossi M, Papa A, Rengo C, Rengo F. Source: American Journal of Therapeutics. 1997 May-June; 4(5-6): 181-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10423609&dopt=Abstract

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Radial, carotid and aortic distensibility in congestive heart failure: effects of highdose angiotensin-converting enzyme inhibitor or low-dose association with angiotensin type 1 receptor blockade. Author(s): Giannattasio C, Achilli F, Failla M, Capra A, Vincenzi A, Valagussa F, Mancia G. Source: Journal of the American College of Cardiology. 2002 April 17; 39(8): 1275-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11955844&dopt=Abstract

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Randomized, double-blind, placebo-controlled, pilot trial of infliximab, a chimeric monoclonal antibody to tumor necrosis factor-alpha, in patients with moderate-tosevere heart failure: results of the anti-TNF Therapy Against Congestive Heart Failure (ATTACH) trial. Author(s): Chung ES, Packer M, Lo KH, Fasanmade AA, Willerson JT; Anti-TNF Therapy Against Congestive Heart Failure Investigators. Source: Circulation. 2003 July 1; 107(25): 3133-40. Epub 2003 June 09. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12796126&dopt=Abstract

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Rationale for the use of aldosterone antagonists in congestive heart failure. Author(s): Rocha R, Williams GH. Source: Drugs. 2002; 62(5): 723-31. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11929327&dopt=Abstract

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Re: Ma, et al., Electrocardiographic manifestations: digitalis toxicity and Kumar, et al., A rare cause of congestive heart failure, The Journal of Emergency Medicine, 2001; 20:145-52, 153-7. Author(s): Martinez-Lopez JI. Source: The Journal of Emergency Medicine. 2002 April; 22(3): 299; Author Reply 299300. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11932098&dopt=Abstract

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Recognition and clinical management of depression in congestive heart failure. Author(s): Friedman EH. Source: Archives of Internal Medicine. 2002 February 11; 162(3): 362. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11822938&dopt=Abstract

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Relation between neurohormonal activation and enhanced ventilatory response to exercise in patients with chronic congestive heart failure. Author(s): Kinugawa T, Tomikura Y, Ogino K, Osaki S, Kato M, Igawa O, Hisatome I, Shigemasa C. Source: The American Journal of Cardiology. 2002 March 1; 89(5): 604-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11867051&dopt=Abstract

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Relation of aldosterone “escape” despite angiotensin-converting enzyme inhibitor administration to impaired exercise capacity in chronic congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. Author(s): Cicoira M, Zanolla L, Franceschini L, Rossi A, Golia G, Zeni P, Caruso B, Zardini P. Source: The American Journal of Cardiology. 2002 February 15; 89(4): 403-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11835920&dopt=Abstract

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Relationship between interleukin-6 production in the lungs and pulmonary vascular resistance in patients with congestive heart failure. Author(s): Mabuchi N, Tsutamoto T, Wada A, Ohnishi M, Maeda K, Hayashi M, Kinoshita M. Source: Chest. 2002 April; 121(4): 1195-202. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11948053&dopt=Abstract

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Renal and cardiac function during alpha1-beta-blockade in congestive heart failure. Author(s): Heitmann M, Davidsen U, Stokholm KH, Rasmussen K, Burchardt H, Petersen EB. Source: Scandinavian Journal of Clinical and Laboratory Investigation. 2002; 62(2): 97104. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12004934&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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Selective aldosterone blockade with eplerenone in patients with congestive heart failure. Author(s): Salam AM. Source: Expert Opinion on Investigational Drugs. 2003 August; 12(8): 1423-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12882627&dopt=Abstract

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Serum magnesium aberrations in furosemide (frusemide) treated patients with congestive heart failure: pathophysiological correlates and prognostic evaluation. Author(s): Cohen N, Almoznino-Sarafian D, Zaidenstein R, Alon I, Gorelik O, Shteinshnaider M, Chachashvily S, Averbukh Z, Golik A, Chen-Levy Z, Modai D. Source: Heart (British Cardiac Society). 2003 April; 89(4): 411-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12639869&dopt=Abstract

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Setting up a clinic for congestive heart failure patients. Author(s): Paul S. Source: Critical Care Nurse. 2000 December; 20(6): 81-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11878262&dopt=Abstract

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Stability of B-type natriuretic peptide levels during exercise in patients with congestive heart failure: implications for outpatient monitoring with B-type natriuretic peptide. Author(s): McNairy M, Gardetto N, Clopton P, Garcia A, Krishnaswamy P, Kazanegra R, Ziegler M, Maisel AS. Source: American Heart Journal. 2002 March; 143(3): 406-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11868044&dopt=Abstract

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Strength/endurance training versus endurance training in congestive heart failure. Author(s): Delagardelle C, Feiereisen P, Autier P, Shita R, Krecke R, Beissel J. Source: Medicine and Science in Sports and Exercise. 2002 December; 34(12): 1868-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12471289&dopt=Abstract

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Successful implantation of transveneous biventricular permanent pacemaker for refractory congestive heart failure: the first case-report in Thailand. Author(s): Sriratanasathavorn C, Chotinaiwattarakul C, Nutakul T, Khaosaard B. Source: J Med Assoc Thai. 2003 May; 86 Suppl 1: S116-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12866778&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 after withdrawal of dofetilide in patients with congestive heart failure and a short baseline QTc interval; a follow-up on the Diamond-CHF QT substudy. Author(s): Brendorp B, Torp-Pedersen C, Elming H, Kober L. Source: European Heart Journal. 2003 February; 24(3): 274-9. Erratum In: Eur Heart J. 2003 June; 24(12): 1176. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12590905&dopt=Abstract

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Sympatholysis and cardiac sympathetic nerve function in the treatment of congestive heart failure. Author(s): Liang CS. Source: Journal of the American College of Cardiology. 2003 August 6; 42(3): 549-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12906987&dopt=Abstract

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Systolic blood pressure, diastolic blood pressure, and pulse pressure as predictors of risk for congestive heart failure in the Framingham Heart Study. Author(s): Haider AW, Larson MG, Franklin SS, Levy D; Framingham Heart Study. Source: Annals of Internal Medicine. 2003 January 7; 138(1): 10-6. Summary for Patients In: http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12513039&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 effects of dobutamine on cardiac sympathetic activity in patients with congestive heart failure. Author(s): Al-Hesayen A, Azevedo ER, Newton GE, Parker JD. Source: Journal of the American College of Cardiology. 2002 April 17; 39(8): 1269-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11955843&dopt=Abstract

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The paradox of increased natriuretic hormones in congestive heart failure patients: does the endocrine heart also fail in heart failure? Author(s): Goetze JP, Kastrup J, Rehfeld JF. Source: European Heart Journal. 2003 August; 24(16): 1471-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12919769&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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Tolerability of beta-blocker initiation and titration in the Metoprolol CR/XL Randomized Intervention Trial in Congestive Heart Failure (MERIT-HF). Author(s): Gottlieb SS, Fisher ML, Kjekshus J, Deedwania P, Gullestad L, Vitovec J, Wikstrand J; MERIT-HF Investigators. Source: Circulation. 2002 March 12; 105(10): 1182-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11889011&dopt=Abstract

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Treatment of congestive heart failure. Author(s): Stevenson LW. Source: Jama : the Journal of the American Medical Association. 2002 May 1; 287(17): 2209-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11980515&dopt=Abstract

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Treatment of congestive heart failure. Author(s): Jerant AF. Source: Jama : the Journal of the American Medical Association. 2002 May 1; 287(17): 2209-10; Author Reply 2210. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11980514&dopt=Abstract

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Treatment of congestive heart failure. Author(s): de Denus S, Spinler SA. Source: Jama : the Journal of the American Medical Association. 2002 May 1; 287(17): 2209; Author Reply 2210. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11980513&dopt=Abstract

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Treatment of congestive heart failure. Author(s): Brumley RD. Source: Jama : the Journal of the American Medical Association. 2002 May 1; 287(17): 2209; Author Reply 2210. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11980512&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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Underutilisation of ACE inhibitors in patients with congestive heart failure. Author(s): Bungard TJ, McAlister FA, Johnson JA, Tsuyuki RT. Source: Drugs. 2001; 61(14): 2021-33. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11735631&dopt=Abstract

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Update on recent clinical trials in congestive heart failure. Author(s): Betkowski AS, Hauptman PJ. Source: Current Opinion in Cardiology. 2000 July; 15(4): 293-303. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11139094&dopt=Abstract

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Update on treatment for congestive heart failure. Author(s): Sucov A. Source: Medicine and Health, Rhode Island. 2002 February; 85(2): 64-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11881170&dopt=Abstract

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Uric acid--a marker for systemic inflammatory response in patients with congestive heart failure? Author(s): Olexa P, Olexova M, Gonsorcik J, Tkac I, Kisel'ova J, Olejnikova M. Source: Wiener Klinische Wochenschrift. 2002 March 28; 114(5-6): 211-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12238311&dopt=Abstract

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Use of antiarrhythmics and implantable cardioverter-defibrillators in congestive heart failure. Author(s): Estes NA 3rd, Weinstock J, Wang PJ, Homoud MK, Link MS. Source: The American Journal of Cardiology. 2003 March 20; 91(6A): 45D-52D. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12670642&dopt=Abstract

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Use of beta-blockers in chronic congestive heart failure. Author(s): Mahanonda N, Samranthin M, Panyarachun S. Source: J Med Assoc Thai. 2000 October; 83(10): 1240-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11143491&dopt=Abstract

•

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

•

Usefulness of biventricular pacing in patients with congestive heart failure and right bundle branch block. Author(s): Garrigue S, Reuter S, Labeque JN, Jais P, Hocini M, Shah DC, Haissaguerre M, Clementy J. Source: The American Journal of Cardiology. 2001 December 15; 88(12): 1436-41, A8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11741571&dopt=Abstract

•

Utility of a rapid B-natriuretic peptide assay in differentiating congestive heart failure from lung disease in patients presenting with dyspnea. Author(s): Morrison LK, Harrison A, Krishnaswamy P, Kazanegra R, Clopton P, Maisel A. Source: Journal of the American College of Cardiology. 2002 January 16; 39(2): 202-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11788208&dopt=Abstract

•

Utility of B-type natriuretic peptide in the diagnosis of congestive heart failure in an urgent-care setting. Author(s): Dao Q, Krishnaswamy P, Kazanegra R, Harrison A, Amirnovin R, Lenert L, Clopton P, Alberto J, Hlavin P, Maisel AS. Source: Journal of the American College of Cardiology. 2001 February; 37(2): 379-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11216950&dopt=Abstract

•

Validating facemask use for gas exchange analysis in patients with congestive heart failure. Author(s): Baran DA, Rosenwinkel E, Spierer DK, Lisker J, Whelan J, Rosa M, Goldsmith RL. Source: Journal of Cardiopulmonary Rehabilitation. 2001 March-April; 21(2): 94-100. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11314290&dopt=Abstract

110 Congestive Heart Failure

•

Validation of a treadmill exercise test protocol with improved metabolic plateau formation in patients with chronic congestive heart failure. Author(s): Scott AC, Francis DP, Davies LC, Coats AJ, Piepoli MF. Source: The American Journal of Cardiology. 2001 June 1; 87(11): 1328-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11377372&dopt=Abstract

•

Validity of the right ventricular Doppler index for assessment of severity of congestive heart failure in patients with dilated cardiomyopathy. Author(s): Izumi C, Kibira S, Watanabe H, Nakagawa M, Wen S, Fujii H, Saito T, Matsuoka H, Miura M. Source: Heart and Vessels. 1999; 14(5): 232-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10830919&dopt=Abstract

•

Value of Doppler index combining systolic and diastolic myocardial performance in predicting cardiopulmonary exercise capacity in patients with congestive heart failure: effects of dobutamine. Author(s): Parthenakis FI, Kanakaraki MK, Kanoupakis EM, Skalidis EI, Diakakis GF, Filippou OK, Vardas PE. Source: Chest. 2002 June; 121(6): 1935-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12065360&dopt=Abstract

•

Vascular endothelial growth factor and soluble P-selectin in acute and chronic congestive heart failure. Author(s): Chin BS, Chung NA, Gibbs CR, Blann AD, Lip GY. Source: The American Journal of Cardiology. 2002 December 1; 90(11): 1258-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12450612&dopt=Abstract

•

Vasopeptidase inhibitor reduces inhospital costs for patients with congestive heart failure: results from the IMPRESS trial. Inhibition of Metallo Protease by BMS186716 in a Randomized Exercise and Symptoms Study in Subjects With Heart Failure. Author(s): Eisenstein EL, Nelson CL, Simon TA, Smitten AL, Lapuerta P, Mark DB. Source: American Heart Journal. 2002 June; 143(6): 1112-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12075271&dopt=Abstract

•

Ventricular dyssynchrony in dilated cardiomyopathy: the role of biventricular pacing in the treatment of congestive heart failure. Author(s): Aranda JM Jr, Schofield RS, Leach D, Conti JB, Hill JA, Curtis AB. Source: Clin Cardiol. 2002 August; 25(8): 357-62. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12173901&dopt=Abstract

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Ventricular unloading and myocyte recovery: insight gained into the pathophysiology of congestive heart failure. Author(s): Margulies KB. Source: Current Cardiology Reports. 2000 May; 2(3): 181-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10980891&dopt=Abstract

•

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

•

Vitamin C inhibits endothelial cell apoptosis in congestive heart failure. Author(s): Rossig L, Hoffmann J, Hugel B, Mallat Z, Haase A, Freyssinet JM, Tedgui A, Aicher A, Zeiher AM, Dimmeler S. Source: Circulation. 2001 October 30; 104(18): 2182-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11684628&dopt=Abstract

•

Weight loss of 146 kg with diet and reversal of severe congestive heart failure in a young, morbidly obese patient. Author(s): Zuber M, Kaeslin T, Studer T, Erne P. Source: The American Journal of Cardiology. 1999 October 15; 84(8): 955-6, A8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10532524&dopt=Abstract

•

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. 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

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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

•

What is the differential diagnosis for patients with symptoms of congestive heart failure (CHF) and normal systolic function? Author(s): Edens-Bartholomew N, Newton WP. Source: The Journal of Family Practice. 2000 November; 49(11): 1047. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11093571&dopt=Abstract

112 Congestive Heart Failure

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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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CHAPTER 2. NUTRITION AND CONGESTIVE HEART FAILURE Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and congestive heart failure.

Finding Nutrition Studies on Congestive 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.7 The IBIDS includes references and citations to both human and animal research studies. As a service of the ODS, access to the IBIDS database is available free of charge at the following Web address: http://ods.od.nih.gov/databases/ibids.html. After entering the search area, you have three choices: (1) IBIDS Consumer Database, (2) Full IBIDS Database, or (3) Peer Reviewed Citations Only. Now that you have selected a database, click on the “Advanced” tab. An advanced search allows you to retrieve up to 100 fully explained references in a comprehensive format. Type “congestive heart failure” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.

7

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

114 Congestive Heart Failure

The following is a typical result when searching for recently indexed consumer information on congestive heart failure: •

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

•

Antenatal diagnosis and treatment of a case of fetal goitrous hypothyroidism associated with high-output cardiac failure. Author(s): Department of Obstetrics, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka University Graduate School of Medicine, Osaka, Japan. Source: Morine, M Takeda, T Minekawa, R Sugiyama, T Wasada, K Mizutani, T Suehara, N Ultrasound-Obstet-Gynecol. 2002 May; 19(5): 506-9 0960-7692

•

Bradykinin infusion in chronic cardiac failure and the effects of captopril. Author(s): Department of Medicine, Royal Victoria Hospital, BT12 6BA, Belfast, UK. Source: Maguire, S M McAuley, D McGurk, C Nugent, A G Johnston, G D Nicholls, D P Eur-J-Heart-Fail. 2001 December; 3(6): 671-7 1388-9842

•

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

•

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

•

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

•

Drug absorption in congestive heart failure: impact on management. Author(s): Division of Clinical Pharmacology and Hypertension, Medical College of Virginia of Virginia Commonwealth University, Richmond 23298-0160, USA. Source: Sica, D A Prog-Cardiovasc-Nurs. 1999 Winter; 14(1): 30-2 0889-7204

•

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): Department of Internal Medicine, University of Palermo, Palermo, Italy. Source: Paterna, S Di Pasquale, P Parrinello, G Amato, P Cardinale, A Follone, G Giubilato, A Licata, G Eur-J-Heart-Fail. 2000 September; 2(3): 305-13 1388-9842

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End-stage cardiac failure in a morbidly obese patient treated by biliopancreatic diversion and cardiac transplantation. Author(s): Baylor College of Medicine, Houston, TX, USA. [email protected] Source: Taylor, T V Bozkurt, B Shayani, P Lafuente, J Noon, G Obes-Surg. 2002 June; 12(3): 416-8 0960-8923

•

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

•

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

•

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. 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

•

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

•

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

•

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

•

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-

116 Congestive Heart Failure

•

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

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

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

•

Antenatal diagnosis and treatment of a case of fetal goitrous hypothyroidism associated with high-output cardiac failure. Author(s): Department of Obstetrics, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka University Graduate School of Medicine, Osaka, Japan. Source: Morine, M Takeda, T Minekawa, R Sugiyama, T Wasada, K Mizutani, T Suehara, N Ultrasound-Obstet-Gynecol. 2002 May; 19(5): 506-9 0960-7692

•

Bradykinin infusion in chronic cardiac failure and the effects of captopril. Author(s): Department of Medicine, Royal Victoria Hospital, BT12 6BA, Belfast, UK. Source: Maguire, S M McAuley, D McGurk, C Nugent, A G Johnston, G D Nicholls, D P Eur-J-Heart-Fail. 2001 December; 3(6): 671-7 1388-9842

•

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

•

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

•

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

•

Drug absorption in congestive heart failure: impact on management. Author(s): Division of Clinical Pharmacology and Hypertension, Medical College of Virginia of Virginia Commonwealth University, Richmond 23298-0160, USA. Source: Sica, D A Prog-Cardiovasc-Nurs. 1999 Winter; 14(1): 30-2 0889-7204

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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): Department of Internal Medicine, University of Palermo, Palermo, Italy. Source: Paterna, S Di Pasquale, P Parrinello, G Amato, P Cardinale, A Follone, G Giubilato, A Licata, G Eur-J-Heart-Fail. 2000 September; 2(3): 305-13 1388-9842

•

End-stage cardiac failure in a morbidly obese patient treated by biliopancreatic diversion and cardiac transplantation. Author(s): Baylor College of Medicine, Houston, TX, USA. [email protected] Source: Taylor, T V Bozkurt, B Shayani, P Lafuente, J Noon, G Obes-Surg. 2002 June; 12(3): 416-8 0960-8923

•

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

•

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

•

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. 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

•

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

•

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

•

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

118 Congestive Heart Failure

•

•

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-

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

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

•

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

•

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

•

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

•

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/

•

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

•

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

•

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

•

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

Nutrition

•

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

•

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

•

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

•

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

•

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

•

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

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The following is a specific Web list relating to congestive 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

•

Minerals 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

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Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10020,00.html Creatine Monohydrate Source: Healthnotes, Inc.; www.healthnotes.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 •

Food and Diet 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 CONGESTIVE HEART FAILURE Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to congestive 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 congestive 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 “congestive 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 congestive heart failure: •

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 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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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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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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Angioplasty of residual stenosis after severe anteroseptal myocardial infarction: is it able to improve systolic function and to prevent cardiac failure? Author(s): Toussaint M, Guyomard F, Meliani A, Tran-Thanh X, Jouannon C, Durup F, Devaux JY. Source: European Journal of Heart Failure : Journal of the Working Group on Heart Failure of the European Society of Cardiology. 2003 January; 5(1): 81-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12559219&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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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 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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Coenzyme Q10: a vital therapeutic nutrient for the heart with special application in congestive heart failure. Author(s): Sinatra ST.

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Source: Conn Med. 1997 November; 61(11): 707-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9419958&dopt=Abstract •

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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Creatine supplementation in congestive heart failure. Author(s): Field ML. Source: Cardiovascular Research. 1996 January; 31(1): 174-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8849604&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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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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Echocardiographic features of peripartum cardiac failure: the Zaria syndrome. Author(s): Danbauchi SS.

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Source: Trop Doct. 2002 January; 32(1): 24-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11991020&dopt=Abstract •

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. 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

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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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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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Factors contributing to the decision for euthanasia of dogs with congestive heart failure. Author(s): Mallery KF, Freeman LM, Harpster NK, Rush JE. Source: J Am Vet Med Assoc. 1999 April 15; 214(8): 1201-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10212683&dopt=Abstract

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Feasibility of paclitaxel in a patient with anthracycline-induced congestive heart failure. Author(s): Colleoni M, Nelli P, Vicario G, Sgarbossa G, Pancheri F, Manente P.

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Source: European Journal of Cancer (Oxford, England : 1990). 1997 February; 33(2): 3212. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9135512&dopt=Abstract •

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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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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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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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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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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Magnesium supplementation in patients with congestive heart failure. Author(s): Costello RB, Moser-Veillon PB, DiBianco R.

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Source: Journal of the American College of Nutrition. 1997 February; 16(1): 22-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9013430&dopt=Abstract •

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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Metabolic and nutritional support in acute cardiac failure. Author(s): Berger MM, Mustafa I. Source: Current Opinion in Clinical Nutrition and Metabolic Care. 2003 March; 6(2): 195201. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12589189&dopt=Abstract

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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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Neurobiology of respiratory-pattern training in congestive heart failure. Author(s): Friedman EH. Source: European Heart Journal. 1999 July; 20(14): 1052-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10382008&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.

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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 •

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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Profound neonatal congestive heart failure caused by maternal consumption of blue cohosh herbal medication. Author(s): Jones TK, Lawson BM. Source: The Journal of Pediatrics. 1998 March; 132(3 Pt 1): 550-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9544922&dopt=Abstract

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Protective effects of Mu-Fang-Ji-Tang against myocardial injury in a murine model of congestive heart failure induced by viral myocarditis. Author(s): Wang WZ, Matsumori A, Matoba Y, Matsui S, Sato Y, Hirozane T, Shioi T, Sasayama S. Source: Life Sciences. 1998; 62(13): 1139-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9519794&dopt=Abstract

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Reversible congestive heart failure caused by myocardial hibernation. Author(s): Wilson JM. Source: Texas Heart Institute Journal / from the Texas Heart Institute of St. Luke's Episcopal Hospital, Texas Children's Hospital. 1999; 26(1): 19-27. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10217467&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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The effect of dietary creatine supplementation on skeletal muscle metabolism in congestive heart failure. Author(s): Andrews R, Greenhaff P, Curtis S, Perry A, Cowley AJ. Source: European Heart Journal. 1998 April; 19(4): 617-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9597411&dopt=Abstract

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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 thinking on TCM differential treatment of congestive heart failure. Author(s): Liang D, Zhang M. 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

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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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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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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. 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

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 congestive 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 Amyloidosis Source: Integrative Medicine Communications; www.drkoop.com Cardiac Arrhythmia Source: Healthnotes, Inc.; www.healthnotes.com Cardiomyopathy Source: Healthnotes, Inc.; www.healthnotes.com Cardiovascular Disease Overview Source: Healthnotes, Inc.; www.healthnotes.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 Diabetes Mellitus Source: Integrative Medicine Communications; www.drkoop.com Dysmenorrhea Source: Healthnotes, Inc.; www.healthnotes.com Edema Source: Healthnotes, Inc.; www.healthnotes.com

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Edema 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 Hypertension Source: Healthnotes, Inc.; www.healthnotes.com Hypertension Source: Integrative Medicine Communications; www.drkoop.com Menopausal Symptoms (other Than Osteoporosis) Source: Prima Communications, Inc.www.personalhealthzone.com Muscular Dystrophy Source: Integrative Medicine Communications; www.drkoop.com Myocardial Infarction 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 Water Retention 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

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Chinese Medicine Hongshen Alternative names: Red Ginseng; Radix Ginseng Rubra Source: Chinese Materia Medica

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Herbs and Supplements Amiloride Source: Healthnotes, Inc.; www.healthnotes.com Amino Acids Overview Source: Healthnotes, Inc.; www.healthnotes.com Arginine Source: Healthnotes, Inc.; www.healthnotes.com Arginine Source: Prima Communications, Inc.www.personalhealthzone.com Asian Ginseng Alternative names: Panax ginseng Source: Integrative Medicine Communications; www.drkoop.com Astragalus Sp Alternative names: Vetch, Rattlepod, Locoweed; Astragalus sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Black Cohosh Source: Prima Communications, Inc.www.personalhealthzone.com Blue Cohosh Alternative names: Caulophyllum thalictroides Source: Healthnotes, Inc.; www.healthnotes.com Caulophyllum Alternative names: Blue Cohosh; Caulophyllum thalictroides (MICH.) Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org 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 (coq10) Source: Prima Communications, Inc.www.personalhealthzone.com Coleus Alternative names: Coleus forskohlii Source: Healthnotes, Inc.; www.healthnotes.com Crataegus Alternative names: Hawthorn; Crataegus oxyacantha L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org

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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 Felodipine Source: Healthnotes, Inc.; www.healthnotes.com Gravel Root Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca 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 Horsetail Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Juniper Berry Source: Prima Communications, Inc.www.personalhealthzone.com Loop Diuretics Source: Healthnotes, Inc.; www.healthnotes.com Loop Diuretics Source: Integrative Medicine Communications; www.drkoop.com

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Loop Diuretics Source: Prima Communications, Inc.www.personalhealthzone.com Nitroglycerin Source: Healthnotes, Inc.; www.healthnotes.com Panax Ginseng Source: Integrative Medicine Communications; www.drkoop.com Sanguinaria Alternative names: Bloodroot; Sanguinaria canadensis L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Taraxacum Officinale Source: Integrative Medicine Communications; www.drkoop.com Taurine Source: Prima Communications, Inc.www.personalhealthzone.com Triamterene Source: Healthnotes, Inc.; www.healthnotes.com

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

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CHAPTER 4. DISSERTATIONS ON CONGESTIVE HEART FAILURE Overview In this chapter, we will give you a bibliography on recent dissertations relating to congestive 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 “congestive heart failure” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on congestive heart failure, we have not necessarily excluded non-medical dissertations in this bibliography.

Dissertations on Congestive 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 congestive 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: •

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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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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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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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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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 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 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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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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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 CONGESTIVE HEART FAILURE Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning congestive heart failure.

Recent Trials on Congestive Heart Failure The following is a list of recent trials dedicated to congestive heart failure.8 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

8

These are listed at www.ClinicalTrials.gov.

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Purpose - Excerpt: A placebo-controlled trial of BiDil added to standard therapy in African-American patients with heart failure. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00047775 •

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 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

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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 •

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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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 Web Site: http://clinicaltrials.gov/ct/show/NCT00043758

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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.

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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 •

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 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

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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. 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

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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 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

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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.

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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 •

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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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

•

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)

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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 •

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

146 Congestive Heart Failure

the safety of MyoCell(tm) implantation via epicardial injection during CABG surgery and its effect on regional myocardial function. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00050765 •

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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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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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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•

Study to Compare the Effects of Two Dosages of Tolvaptan in Congestive Heart Failure Patients Condition(s): Congestive Heart Failure 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

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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 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

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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 “congestive 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 CONGESTIVE 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.9 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “congestive heart failure” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on congestive heart failure, we have not necessarily excluded non-medical patents in this bibliography.

Patents on Congestive Heart Failure By performing a patent search focusing on congestive 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. 9Adapted

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

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The following is an example of the type of information that you can expect to obtain from a patent search on congestive heart failure: •

14723 Receptor, a novel G-protein coupled receptor Inventor(s): Glucksmann; Maria Alexandra (Lexington, MA), Tsai; Fong-Ying (Newton, MA) Assignee(s): Millennium Pharmaceuticals, Inc. (Cambridge, MA) Patent Number: 6,448,005 Date filed: December 8, 1999 Abstract: The present invention relates to a newly identified receptor belonging to the superfamily of G-protein-coupled receptors. The invention also relates to polynucleotides encoding the receptor. The invention further relates to methods using the receptor polypeptides and polynucleotides as a target for diagnosis and treatment in receptor-mediated disorders, specifically, cardiovascular diseases, including congestive heart failure. The invention further relates to drug-screening methods using the receptor polypeptides and polynucleotides to identify agonists and antagonists for diagnosis and treatment. The invention further encompasses agonists and antagonists based on the receptor polypeptides and polynucleotides. The invention further relates to procedures for producing the receptor polypeptides and polynucleotides. Excerpt(s): G-protein coupled receptors (GPCRS) constitute a major class of proteins responsible for transducing a signal within a cell. GPCRs have three structural domains: an amino terminal extracellular domain, a transmembrane domain containing seven transmembrane segments, three extracellular loops, and three intracellular loops, and a carboxy terminal intracellular domain. Upon binding of a ligand to an extracellular portion of a GPCR, a signal is transduced within the cell that results in a change in a biological or physiological property of the cell. GPCRs, along with G-proteins and effectors (intracellular enzymes and channels modulated by G-proteins), are the components of a modular signaling system that connects the state of intracellular second messengers to extracellular inputs. The GPCR protein superfamily can be divided into five families: Family I, receptors typified by rhodopsin and the.beta.2-adrenergic receptor and currently represented by over 200 unique members (Dohlman et al., Annu. Rev. Biochem. 60:653-688 (1991)); Family II, the parathyroid hormone/calcitonin/secretin receptor family (Juppner et al., Science 254:1024-1026 (1991); Lin et al., Science 254:1022-1024 (1991)); Family III, the metabotropic glutamate receptor family (Nakanishi, Science 258 597:603 (1992)); Family IV, the cAMP receptor family, important in the chemotaxis and development of D. discoideum (Klein et al., Science 241:1467-1472 (1988)); and Family V, the fungal mating pheromone receptors such as STE2 (Kurjan, Annu. Rev. Biochem. 61:1097-1129 1992)). Web site: http://www.delphion.com/details?pn=US06448005__

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Carvedilol methanesulfonate Inventor(s): Franchini; Miriam (Allentown, NJ), Venkatesh; Gopadi M. (Bell Brook, OH) Assignee(s): SmithKline Beecham Corporation (Philadelphia, PA) Patent Number: 6,515,010 Date filed: May 15, 2002

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Abstract: This invention relates to carvedilol methanesulfonate, compositions containing this compound and methods of using carvedilol methanesulfonate to treat hypertension, congestive heart failure and angina. Excerpt(s): This invention relates to a pharmaceutically active compound, 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 carvedilol methanesulfonate, which is the methanesulfonate salt of 1-(carbazol-4-yloxy-3-[[2-(o-methoxyphenoxy)ethyl]amino]-2-propanol, compositions containing this compound, and methods of using carvedilol methanesulfonate to treat hypertension, congestive heart failure and angina. U.S. Pat. No 4,503,067 describes a compound which is known as carvedilol. This compound is a novel multiple action drug useful in the treatment of hypertension and angina. Carvedilol is known to be both a competitive non-selective.beta.-adrenoceptor antagonist and a vasodilator. The vasodilatory actions of carvedilol result primarily from.alpha.sub.1 -adrenoceptor blockade, whereas the.beta.-adrenoceptor blocking activity of the drug prevents reflex tachycardia when used in the treatment of hypertension. These multiple actions of carvedilol are responsible for the antihypertensive efficacy of the drug. Also, carvedilol, as a consequence of its antioxidant action in attenuating oxygen free radical-initiated lipid peroxidation, is useful in organ protection, in particular, cardioprotection. Additionally, carvedilol is useful in the treatment of congestive heart failure. The currently marketed formulation of carvedilol is a conventional, swallow tablet and prescribed as a twice-a-day medication in the United States. This formulation is in immediate release form; that is to say the nature of the formulation is such that by the time carvedilol leaves the stomach, it is either in solution or it is in the form of a suspension of fine particles, i.e. a form from which carvedilol can be readily absorbed. Web site: http://www.delphion.com/details?pn=US06515010__ •

Conjunctive analysis of biological marker expression for diagnosing organ failure Inventor(s): Jackowski; George (Kettleby, CA), Stanton; Eric B. (Burlington, CA) Assignee(s): Syn X Pharma (CA) Patent Number: 6,461,828 Date filed: September 4, 2001 Abstract: A diagnostic tool is disclosed for accurately and rapidly diagnosing the condition of an ailing organ. Although applicable to numerous organ and organ systems, this application particularly illustrates the concept of conjunctive marker utilization as it relates to diagnosing and distinguishing congestive heart failure. The invention particularly relates to the conjunctive utilization of cardiac Troponin I (cTn-I) and natriuretic peptide, e.g. ANP, pro-ANP, BNP, pro-BNP and CNP as a retrospective tool for diagnosing the underlying mechanism of heart failure and as a prospective analytical device for monitoring disease progression and efficacy of therapeutic agents. Excerpt(s): This invention relates to the concept of conjunctive utilization of biological markers expressed in response to abnormal pressure, volume change and stress to a particular organ (e.g. N-terminal ANP (pro-ANP) in heart tissue) along with the expression of biological markers that are indicative of tissue damage (e.g. cardiac Troponin I (cTnI), or fibrosis markers for heart tissue) as a diagnostic tool to accurately and rapidly diagnose the condition of the ailing organ. Although this concept is applicable to numerous organ and organ systems, this application will particularly

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illustrate the concept of conjunctive marker utilization with respect to the heart, specifically with respect to congestive heart failure. The invention particularly relates to the conjunctive utilization of cardiac Troponin I (cTnI) and natriuretic peptides, e.g. brain natriuretic peptide (BNP), N-terminai BNP (pro-BNP)), c-type natriuretic peptide (CNP), atrial natriuretic peptide (ANP), and N-terminal ANP (pro-ANP) as a retrospective tool for diagnosing the underlying mechanism of heart failure and as a prospective analytical device for monitoring disease progression and efficacy of therapeutic agents. Congestive heart failure (CHF) effects approximately 4.8 million Americans. About 400,000 new cases are diagnosed annually and the condition is responsible for approximately 200,000 deaths per year. These statistics, in conjunction with the approximately;1 million hospitalizations annually attributable to CHF, result in an annual expenditure on the order of $10 billion. The underlying reasons for this failure in heart functionality are varied. Thinning and weakening of the ventricle walls leads to dilation and a loss of pumping ability (systolic dysfunction). Alternatively, loss of elasticity results in a stiffening, which may result in a diminished volume of the heart's chambers and loss of pumping capacity (diastolic dysfunction) and cardiac output. Additionally, abnormalities in the functioning of the heart's valves can lead to insufficient cardiac output, for which the body attempts to compensate by causing the heart to increase its heart rate, hypertrophy and/or dilate. The compensation mechanisms utilized by the body may lead to architectural changes in the form of remodeling (especially after MI) or adaptation of the heart muscle, ultimately leading to irrevocable loss of function. Related causes of cardiac failure may be one or more conditions such as coronary artery disease, ischemic heart damage, e.g. damage resulting from a heart attack, uncontrolled hypertension, the direct and/or indirect effects of diabetes on the heart, valvular heart disease, cardiomyopathy, autoimmune response, disease and abuse by external agents such as alcohol, tobacco, anabolic steroids, and the like. Web site: http://www.delphion.com/details?pn=US06461828__ •

Dual chamber pacing system having time-adaptive AV delay Inventor(s): Heynen; Henri G. M. (Geleen, NL), Struble; Chester (Eijsden, NL) Assignee(s): Medtronic, Inc. (Minneapolis, MN) Patent Number: 6,507,756 Date filed: April 3, 2000 Abstract: Rate responsive pacing systems that employ a time-dependent AV delay in the pacing hearts in Congestive Heart Failure (CHF) with Dilated Cardiomyopathy (DCM) (a CHF/DCM heart) during a post-implant Time-Adaptive period are disclosed. A starting or initial AV delay is set to an intrinsic AV delay time interval exhibited by the patient's heart at the time of implant. A chronic AV delay is then set to a therapeutic AV delay time interval that is shorter than the intrinsic AV delay time interval and alleviates symptoms of the CHF/DCM heart. A Time-Adaptive AV delay (TA-AV delay) is employed during a post-implant Time-Adaptive period that gradually changes the initial AV delay to the chronic AV delay at the end of the post-implant Time-Adaptive period. Excerpt(s): The present invention relates to dual chamber pacing systems, including rate responsive pacing systems, and more particularly to the employment of a timedependent AV delay for pacing hearts in Congestive Heart Failure (CHF) with Dilated Cardiomyopathy (DCM). Dual chamber pacing systems operating in the multi-

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programmable, DDD and DDDR pacing modes have been widely adopted in implantable dual chamber pacemakers and certain implantable cardioverter/defibrillators (ICDs) for providing atrial and ventricular (AV) synchronized pacing on demand. A DDD pacemaker implantable pulse generator (IPG) includes an atrial sense amplifier to detect atrial depolarizations or P-waves and generate an atrial sense event (A-EVENT) signal, a ventricular sense amplifier to detect ventricular depolarizations or R-waves and generate a ventricular sense event (VEVENT) signal, atrial and ventricular pacing pulse generators providing atrial and ventricular pacing (A-PACE and V-PACE) pulses, respectively, and an operating system governing pacing and sensing functions. If the atria fail to spontaneously beat within a pre-defined time interval (atrial escape interval), the pacemaker supplies an A-PACE pulse to the atria through an appropriate lead system. The IPG supplies a V-PACE pulse to the ventricles through an appropriate lead system at the time-out of an AV delay timed from a preceding A-EVENT or generation of an A-PACE pulse unless a nonrefractory V-EVENT is generated in response to an R-wave during the AV delay. Such AV synchronous pacemakers which perform this function have the capability of tracking the patient's natural sinus rhythm and preserving the hemodynamic contribution of the atrial contraction over a wide range of heart rates. The rate-adaptive DDDR pacing mode functions in the above-described manner but additionally provides rate modulation of a pacing escape interval between a programmable lower rate and an upper rate limit (URL) as a function of a physiologic signal or rate control parameter (RCP) developed by one or more physiologic sensors and related to the need for cardiac output. In the DDDR pacing mode, reliance on the intrinsic atrial heart rate is preferred if it is appropriately between the URL and the programmed lower rate. At times when the intrinsic atrial rate is inappropriately high, a variety of "mode switching" schemes for effecting switching between tracking modes and non-tracking modes (and a variety of transitional modes) based on the relationship between the atrial rate and the sensor derived pacing rate have been proposed as exemplified by commonly assigned U.S. Pat. No. 5,144,949, incorporated herein by reference in its entirety. Web site: http://www.delphion.com/details?pn=US06507756__ •

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-2-

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thiophenepropionic 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 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

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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 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__ •

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-2-

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thiophenepropionic 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. Web site: http://www.delphion.com/details?pn=US06558699__ •

Implantable cardiac rhythm management device for assessing status of CHF patients Inventor(s): Hopper; Donald L. (Maple Grove, MN), Jones; Bruce R. (Hopkins, MN), Nelson; James P. (Lino Lakes, MN), Stahmann; Jeffrey E. (Ramsey, MN) Assignee(s): Cardiac Pacemakers, Inc. (St. Paul, MN) Patent Number: 6,459,929 Date filed: April 12, 2000 Abstract: A method and apparatus for providing congestive heart failure therapy status. An electronic device, preferably a cardiac rhythm management device, capable of measuring transthoracic impedance and for sensing a level of physical activity is implanted in a patient. The transthoracic impedance signal is processed to obtain an estimate of the subject's minute ventilation, respiratory rate, tidal volume, inspiratory rate and expiratory rate. From accelerometer measured activity, an estimate is obtained of oxygen uptake, carbon dioxide production and work rate. Ratios of tidal volume to respiratory rate, tidal volume to inspiratory time, tidal volume to expiratory time, heart rate to minute ventilation, respiratory rate to minute ventilation, tidal volume to minute ventilation, minute ventilation to oxygen uptake, minute ventilation to carbon dioxide production, minute ventilation to work rate, heart rate to work rate, oxygen uptake to heart rate and other ratios are meaningful status indicators for assessing the efficacy of particular therapy regimens to CHF patients. Excerpt(s): This invention relates generally to an apparatus and method for treating and assessing the efficacy of such treatment of CHF patients, and more particularly to an improved cardiac rhythm management device incorporating circuitry for sensing respiratory, heart rate and/or activity-related parameters. Other rate adaptive CRMs have incorporated some form of an activity sensor, such as an accelerometer, for developing a control signal that varies with a patient's level of physical activity. This control signal is then used to vary the pacing rate of a rate adaptive CRM device to maintain an appropriate pacing rate for the level of exercise being exerted. In implantable CRM devices especially designed for treating patients with CHF, one approach that has proved successful involves the automatic optimization of the AV delay of an implantable, dual-chamber pacemaker. For a general description of the prior art relating to pacemakers for treating CHF, reference is made to the Baumann U.S. Pat. No. 5,800,471, the teachings of which are incorporated herein by reference as if set forth in full.

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Web site: http://www.delphion.com/details?pn=US06459929__ •

Implantable device and method for long-term detection and monitoring of congestive heart failure Inventor(s): Erlebacher; Jay (55 Woodland Park Dr., Tenafly, NJ 07670) Assignee(s): none reported Patent Number: 6,473,640 Date filed: January 20, 2000 Abstract: The implantable device for long term monitoring of congestive heart failure employs a signal generator, such as within a pacemaker, to generate an electrical signal which is monitored to obtain a single or dual frequency measurement that can independently measure systemic venous and pulmonary (lung) impedance. The device is able to detect changes in resistance to a flow of current in the systemic venous system and changes in impedance to a flow of current through a lung to thereby indicate separate detection of systemic venous and pulmonary congestion. Excerpt(s): This invention relates to an implantable device and method for long term detection and monitoring of congestive heart failure. More particularly, this invention relates to a device and method of assessing pulmonary congestive and/or systemic venous congestion. As is known, congestive heart failure (CHF) in a patient is caused, in part, by a build-up of fluid in the lungs and body of a patient. Typically, the of buildup of fluid in the. lungs and body (i.e. edema) is a sign of failing heart circulation, for example, as described in U.S. Pat. No. 5,876,353. Accordingly, attempts have been made for detecting the occurrence of edema in the lungs, for example, using impedance monitoring. In some cases, proposals have been made to take external or internal measurements of impedance as an index of lung water content (edema). However, suitable results have not been obtained to permit long term monitoring of pulmonary and systemic venous congestion. By way of example, U.S. Pat. Nos. 5,876,353 and 5,957,861 describe the use of an impedance monitor for discerning edema in a patient through the use of respiratory rate and direct current (DC) impedance. In particular, an impedance and respiratory monitoring circuit is added to a pacemaker system in order to obtain measurements of transthoracic impedance and respiratory rate. These measurements are taken over a long term to obtain a long term average signal so that differences can be used to algorithmically process the variance over time for use to assess the amount of tissue edema over the long term changing condition. However, such techniques fail to distinguish between left heart failure causing lung (pulmonary) edema and right heart failure causing systemic venous congestion. In clinical cases, right and left heart failure may occur in concert or independent of each other. DC impedance in particular is more reflective of systemic venous congestion and may be insensitive for detection of pulmonary edema. Furthermore, respiratory rate changes are a relatively late consequence of CHF and may not occur far enough in advance of dangerous clinical consequences to permit intervention. In addition, respiratory rate changes are not specific to CHF. They occur with exacerbations of various ling diseases such as emphysema, asthma and the like, as well as with anxiety, fever, ascent to high altitudes, and other common conditions. Web site: http://www.delphion.com/details?pn=US06473640__

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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. Web site: http://www.delphion.com/details?pn=US06549806__

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Implantable medical device for monitoring congestive heart failure Inventor(s): Bennett; Tom D. (Shoreview, MN), Deno; D. Curtis (Andover, MN), Hill; Michael R. S. (Minneapolis, MN), Igel; David A. (Lino Lakes, MN), Mulligan; Lawrence J. (Andover, MN) Assignee(s): Medtronic, Inc. (Minneapolis, MN) Patent Number: 6,438,408 Date filed: December 28, 2000 Abstract: An implantable stimulator and monitor measures a group of heart failure parameters indicative of the state of heart failure employing EGM signals, measures of blood pressure including absolute pressure P, developed pressure (DP=systolic Pdiastolic P), and/or dP/dt, and measures of heart chamber volume (V) over one or more cardiac cycles. These parameters include: (1) relaxation or contraction time constant tau (.tau.); (2) mechanical restitution (MR), i.e., the mechanical response of a heart chamber to premature stimuli applied to the heart chamber; (3) recirculation fraction (RF), i.e., the rate of decay of PESP effects over a series of heart cycles; and (4) end systolic elastance (E.sub.ES), i.e., the ratios of end systolic blood pressure P to volume V. These heart failure parameters are determined periodically regardless of patient posture and activity level. However, certain of the parameters are only measured or certain of the data are only stored when the patient heart rate is regular and within a normal sinus range between programmed lower and upper heart rates. The parameter data is associated with a date and time stamp and with other patient data, e.g., patient activity level, and the associated parameter data is stored in IMD memory for retrieval at a later date employing conventional telemetry systems. Incremental changes in the parameter data over time, taking any associated time of day and patient data into account, provide a measure of the degree of change in the heart failure state of the heart. Excerpt(s): The present invention relates generally to implantable medical devices and more specifically to implantable monitors for monitoring signs of acute or chronic cardiac mechanical dysfunction such as congestive heart failure (CHF) or cardiogenic shock to enable a physician to diagnose the condition of the heart and prescribe appropriate therapies. Patients suffering from chronic CHF manifest an elevation of left ventricular end-diastolic pressure, according to the well-known heterometric autoregulation principles espoused by Frank and Starling. This may occur while left ventricular end-diastolic volume remains normal due to a decrease in left ventricular compliance concomitant with increased ventricular wall stiffness. CHF due to chronic hypertension, ischemia, infarct or idiopathic cardiomyopathy is associated with compromised systolic and diastolic function involving decreased atrial and ventricular muscle compliance. These may be conditions associated with chronic disease processes or complications from cardiac surgery with or without specific disease processes. Most heart failure patients do not normally suffer from a defect in the conduction system leading to ventricular bradycardia, but rather suffer from symptoms which may include a general weakening of the contractile function of the cardiac muscle, attendant enlargement thereof, impaired myocardial relaxation and depressed ventricular filling characteristics in the diastolic phase following contraction. Pulmonary edema, shortness of breath, and disruption in systemic blood pressure are associated with acute exacerbations of heart failure. All these disease processes lead to insufficient cardiac output to sustain mild or moderate levels of exercise and proper function of other body organs, and progressive worsening eventually results in cardiogenic shock, arrhythmias, electromechanical dissociation, and death. Such patients are normally treated with drug therapies, including digitalis, which may lead to toxicity and loss of effectiveness. Many

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inotropic drugs have recently become available, targeted at various receptors in the myocyte and designed for the purpose of directly stimulating cardiac tissue in order to increase contractility. However, there exist many possible undesirable side effects, in addition to the fact that these drugs do not always work for their intended purpose. This is especially characteristic of the patient suffering from end-stage heart failure. Web site: http://www.delphion.com/details?pn=US06438408__ •

Method and apparatus for predicting mortality in congestive heart failure patients Inventor(s): Casscells, III; Samuel W. (3656 Wickersham La., Houston, TX 77027), Naghavi; Monteza (Houston, TX), Siadaty; M. Said (Houston, TX) Assignee(s): Casscells, III; Samuel W. (Houston, TX) Patent Number: 6,454,707 Date filed: March 6, 2000 Abstract: Methods of predicting mortality or imminent death in patients with congestive heart failure include detecting changes in the patient's temperature and/or the detection of hypothermia. The invention also relates to devices and kits for implementation of these methods. Excerpt(s): The present invention generally relates to methods of predicting mortality in patients with congestive heart failure, and more particularly to such methods including detection of hypothermia in a congestive heart failure patient. The invention also relates to apparatus, devices and kits for carrying out the methods. Congestive heart failure (CHF) is a leading, and increasing, cause of morbidity and mortality. Numerous predictors of mortality in patients with CHF have been described in the literature. For example, Myers et al.sup.1 reports that in predicting outcome in severe chronic heart failure, peak oxygen uptake (VO.sub.2) surpassed clinical variables, right-heart catheterization data, exercise time, and other exercise test variables. Other prognostic variables have also been identified, including left ventricular ejection function (LVEF), age, creatinine, right ventricular ejection fraction (RVEF), hyponatremia, bilirubin and recently, lymphocyte count. Nevertheless, these variables together account for only a portion of the variance, with the strong predictors usually applying to only a few patients, leaving prognosis uncertain for the individual patient. The ability to accurately predict which patients are likely to have the shortest survival times is particularly needed in the selection of patients for heart transplantation or left ventricular assist device (LVAD) implantation.sup.2-19. An accurate prognosis helps physicians optimize therapies for their patients. Even if in the circumstances a more accurate prognosis would not improve therapy (e.g., when the therapy has already been optimized), most patients and their families want as accurate a prognosis as possible. The invention contemplates a method, apparatus and kit devices for detecting a drop in a patient's body temperature as a means of predicting imminent death in congestive heart failure patients. Web site: http://www.delphion.com/details?pn=US06454707__

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Method and apparatus for treatment of congestive heart failure by improving perfusion of the kidney Inventor(s): Gelfand; Mark (New York, NY), Levin; Howard R. (Teaneck, NJ) Assignee(s): CHF Solutions, Inc. (New York, NY) Patent Number: 6,514,226 Date filed: February 10, 2000 Abstract: A method for treating congestive heart failure (CHF) has been developed that restores kidney renal functions by artificially perfusion of at least one kidney. The kidney is perfused with the patient's blood or other suitable perfusion fluid. A catheter inserted into the aorta of the patient has a distal end that supplies the perfusion fluid into a renal artery of the patient. The catheter may be coupled to an implanted blood pump or to an external supply of perfusion pressure. The restoration of kidney function assists the heart by removing excess fluid, urine and toxin from the patient, and by normalizing the patient's renin-angiotensin system and other neurohormonal substances. The method is applicable to treat chronic and acute CHF. Excerpt(s): The invention generally relates to the treatment of congestive heart failure (CHF). In particular, the invention relates to a method and apparatus to treat patients with congestive heart failure by normalization of kidney perfusion to restore to the patient the benefits of normal kidney functioning. Congestive heart failure (CHF) is a serious condition affecting an estimated 5 million Americans. Increasing prevalence, hospitalizations, and deaths have made CHF a major chronic health condition in the United States. There are an estimated 400,000 new cases of CHF each year. These cases are often first diagnosed as the end stage of cardiac disease. The average mortality rate of CHF is 10 percent after the 1st year and 50 percent after 5 years. Thus, half of the patients diagnosed with CHF will die within 5 years of their diagnosis. The magnitude of the problem is expected to get much worse as more cardiac patients are able to survive and live longer. As patients live longer, the potential for developing CHF increases. In addition, because the incidence of heart failure rises substantially beyond age 65, the prevalence of this condition is likely to increase as the population ages. Web site: http://www.delphion.com/details?pn=US06514226__

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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

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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 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__ •

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

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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__ •

Methods of treating sexual dysfunction in an individual suffering from a retinal disease, class 1 congestive heart failure, or myocardial infarction using a PDE5 inhibitor Inventor(s): Emmick; Jeffrey T. (Plainfield, IN), Ferguson; Kenneth M. (Bothell, WA), Pullman; William E. (Carmel, IN), Whitaker; John S. (Woodinvill, WA) Assignee(s): Lilly Icos, LLC. (Wilmington, DE) Patent Number: 6,451,807 Date filed: April 26, 2000 Abstract: The present invention relates to highly selective phosphodiesterase (PDE) enzyme inhibitors and to their use in methods of treating sexual dysfunction in individuals suffering from a retinal disease, class 1 congestive heart failure, or myocardial infarction. Excerpt(s): The present invention relates to highly selective phosphodiesterase (PDE) enzyme inhibitors and to their use in pharmaceutical articles of manufacture. In particular, the present invention relates to potent inhibitors of cyclic guanosine 3',5'monophosphate specific phosphodiesterase type 5 (PDE5) that when incorporated into a pharmaceutical product are useful for the treatment of sexual dysfunction. The articles of manufacture described herein are characterized by selective PDE5 inhibition, and accordingly, provide a benefit in therapeutic areas where inhibition of PDE5 is desired, with minimization or elimination of adverse side effects resulting from inhibition of other phosphodiesterase enzymes. The biochemical, physiological, and clinical effects of cyclic guanosine 3',5'-monophosphate specific phosphodiesterase (cGMP-specific PDE) inhibitors suggest their utility in a variety of disease states in which modulation of smooth muscle, renal, hemostatic, inflammatory, and/or endocrine function is desired. Type 5 cGMP-specific phosphodiesterase (PDE5) is the major cGMP hydrolyzing enzyme in vascular smooth muscle, and its expression in penile corpus cavernosum has been reported (Taher et al., J. Urol., 149:285A (1993)). Thus, PDE5 is an attractive target in the treatment of sexual dysfunction (Murray, DN&P 6(3):150-56 (1993)). A pharmaceutical product, which provides a PDE5 inhibitor, is currently available and marketed under the trademark VIAGRA.RTM. The active ingredient in VIAGRA.RTM. is sildenafil. The product is sold as an article of manufacture including 25, 50, and 100 mg tablets of sildenafil and a package insert. The package insert provides that sildenafil is a more potent inhibitor of PDE5 than other known phosphodiesterases (greater than 80 fold for PDE1 inhibition, greater than 1,000 fold for PDE2, PDE3, and PDE4 inhibition). The IC.sub.50 for sildenafil against PDE5 has been reported as 3 nM (Drugs of the Future, 22(2), pp. 128-143 (1997)), and as 3.9 nM (Boolell et al., Int. J. of Impotence Res., 8 p. 47-52 (1996)). N.C. Sildenafil is described as having a 4,000-fold selectivity for PDE5 versus PDE3, and only a 10-fold selectivity for PDE5 versus PDE6. Its relative lack

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of selectivity for PDE6 is theorized to be the basis for abnormalities related to color vision. Web site: http://www.delphion.com/details?pn=US06451807__ •

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 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__

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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 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__

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Nitrosated and nitrosylated phosphodiesterase inhibitors, compositions and methods of use Inventor(s): Earl; Richard A. (Westford, MA), Garvey; David S. (Dover, MA), Khanapure; Subhash P. (Clinton, MA), Saenz de Tejada; Inigo (Madrid, ES) Assignee(s): NitroMed, Inc. (Bedford, MA) Patent Number: 6,462,044 Date filed: August 30, 2001 Abstract: The present invention describes novel nitrosated and/or nitrosylated phosphodiesterase inhibitors, and novel compositions containing at least one nitrosated and/or nitrosylated phosphodiesterase inhibitor, and, optionally, one or more compounds that donate, transfer or release nitric oxide, elevate endogenous levels of endothelium-derived relaxing factor, stimulate endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase and/or one or more vasoactive agents. The present invention also provides novel compositions containing at least one

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phosphodiesterase inhibitor, and one or more compounds that donate, transfer or release nitric oxide, elevate endogenous levels of endothelium-derived relaxing factor, stimulate endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase and/or one or more vasoactive agents. The present invention also provides methods for treating or preventing sexual dysfunctions in males and females, for enhancing sexual responses in males and females, and for treating or preventing diseases induced by the increased metabolism of cyclic guanosine 3',5'-monophosphate (cGMP), such as hypertension, pulmonary hypertension, congestive heart failure, renal failure, myocardial infraction, stable, unstable and variant (Prinzmetal) angina, atherosclerosis, cardiac edema, renal insufficiency, nephrotic edema, hepatic edema, stroke, asthma, bronchitis, chronic obstructive pulmonary disease (COPD), cystic fibrosis, dementia, immunodeficiency, premature labor, dysmenorrhoea, benign prostatic hyperplasis (BPH), bladder outlet obstruction, incontinence, conditions of reduced blood vessel patency, e.g., postpercutaneous transluminal coronary angioplasty (post-PTCA), peripheral vascular disease, allergic rhinitis, glucoma, and diseases characterized by disorders of gut motility, e.g., irritable bowel syndrome (IBS). Excerpt(s): This application is related to, not a continuing case to U.S. Pat. Nos. 6,172,060, 6,197,778, 6,177,428, 6,172,068, 6,221,881, 6,232,321, 6,197,782, 6,133,272, and 6,211,179. The present invention describes novel nitrosated and/or nitrosylated phosphodiesterase inhibitors, and novel compositions comprising at least one nitrosated and/or nitrosylated phosphodiesterase inhibitor, and, optionally, at least one compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase, and/or at least one vasoactive agent. The present invention also provides novel compositions comprising at least one phosphodiesterase inhibitor, and at least one compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase, and/or at least one vasoactive agent. The present invention also provides methods for treating or preventing sexual dysfunctions in males and females, for enhancing sexual responses in males and females, and for treating or preventing diseases induced by the increased metabolism of cyclic guanosine 3',5'-monophosphate (cGMP), such as hypertension, pulmonary hypertension, congestive heart failure, renal failure, myocardial infraction, stable, unstable and variant (Prinzmetal) angina, atherosclerosis, cardiac edema, renal insufficiency, nephrotic edema, hepatic edema, stroke, asthma, bronchitis, chronic obstructive pulmonary disease (COPD), cystic fibrosis, dementia, immunodeficiency, premature labor, dysmenorrhoea, benign prostatic hyperplasis (BPH), bladder outlet obstruction, incontinence, conditions of reduced blood vessel patency, e.g., postpercutaneous transluminal coronary angioplasty (post-PTCA), peripheral vascular disease, allergic rhinitis, and glucoma, and diseases characterized by disorders of gut motility, such as irritable bowel syndrome (IBS). Adequate sexual function is a complex interaction of hormonal events and psychosocial relationships. There are four stages to sexual response as described in the International Journal of Gynecology & Obstetrics, 51(3):265-277 (1995). The first stage of sexual response is desire. The second stage of sexual response is arousal. Both physical and emotional stimulation may lead to breast and genital vasodilation and clitoral engorgement (vasocongestion). In the female, dilation and engorgement of the blood vessels in the labia and tissue surrounding the vagina produce the "orgasmic platform," an area at the distal third of the vagina where blood becomes sequestered. Localized perivaginal swelling and vaginal lubrication make up the changes in this stage of sexual response. Subsequently, ballooning of the proximal portion of the vagina and elevation of the uterus occurs. In the male,

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vasodilation of the cavemosal arteries and closure of the venous channels that drain the penis produce an erection. The third stage of sexual response is orgasm, while the fourth stage is resolution. Interruption or absence of any of the stages of the sexual response cycle can result in sexual dysfunction. One study found that 35% of males and 42% of females reported some form of sexual dysfunction. Read et al, J. Public Health Med., 19(4):387-391 (1997). Web site: http://www.delphion.com/details?pn=US06462044__ •

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__

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Porcine cardiomyocytes and their use in treatment of insufficient cardiac function Inventor(s): Dinsmore; Jonathan (Brookline, MA) Assignee(s): Diacrin, Inc. (Charlestown, MA) Patent Number: 6,491,912 Date filed: March 16, 1999 Abstract: Porcine cardiomyocytes and methods for using the cardiomyocytes to treat disorders characterized by insufficient cardiac function are described. The porcine cardiomyocytes are preferably embryonic porcine cardiomyocytes. The porcine cardiomyocytes can be modified to be suitable for transplantation into a xenogeneic subject, such as a human. For example, the porcine cardiomyocytes can be modified such that an antigen (e.g., an MHC class I antigen) on the cardiomyocyte surface which is capable of stimulating an immune response against the cardiomyocytes in a xenogeneic subject is altered (e.g., by contact with an anti-MHC class I antibody, or a fragment or derivative thereof) to inhibit rejection of the cardiomyocyte when introduced into the subject. In one embodiment, the porcine cardiomyocytes are obtained from a pig which is essentially free from organisms or substances which are capable of transmitting infection or disease to the recipient subject. The porcine cardiomyocytes of the present invention can be used to treat disorders characterized by insufficient cardiac function, e.g., congestive heart failure, in a xenogeneic subject by administering the cardiomyocytes to the subject. Excerpt(s): Heart disease is the predominant cause of disability and death in all industrialized nations. In the United States, it accounts for about 335 deaths per 100,000 individuals (approximately 40% of the total mortality) overshadowing cancer, which follows with 183 deaths per 100,000individuals. Four categories of heart disease account for about 85-90% of all cardiac-related deaths. These categories include: ischemic heart disease, hypertensive heart disease and pulmonary hypertensive heart disease, valvular disease, and congenital heart disease. Ischemic heart disease, in its various forms, accounts for about 60-75% of all deaths caused by heart disease. One of the factors that renders ischemic heart disease so devastating is the inability of the cardiac muscle cells to divide and repopulate areas of ischemic heart damage. As a result, cardiac cell loss as a result of injury or disease is irreversible. Human to human heart transplants have become the most effective form of therapy for severe heart damage. Many transplant centers now have one-year survival rates exceeding 80-90% and five-year survival rates above 70% after cardiac transplantation. Infections, hypertension, and renal dysfunction caused by cyclosporin, rapidly progressive coronary atherosclerosis, and inmunosuppressant-related cancers have been major complications however. Heart transplantation, moreover, is limited by the scarcity of suitable donor organs. In addition to the difficulty in obtaining donor organs, the expense of heart transplantation prohibits its widespread application. Another unsolved problem is graft rejection. Foreign hearts and heart cells are poorly tolerated by the recipient and are rapidly destroyed by the immune system in the absence of immunosuppressive drugs. While immunosuppressive drugs may be used to prevent rejection, they also block desirable immune responses such as those against bacterial and viral infections, thereby placing the recipient at risk of infection. There is a clear need, therefore, to address the limitations of the current heart transplantation therapy as treatment for heart disease. To overcome the current limitations of whole heart transplantation to treat heart disorders, the present invention provides cardiomyocytes, compositions including the cardiomyocytes, and methods for treating disorders characterized by insufficient cardiac function by administering the cardiomyocytes to subjects with such disorders. The

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cardiomyocytes of the present invention offer several advantages over whole heart transplantation to treat cardiac disorders. The cardiomyocytes are isolated from pigs, which provide a convenient, relatively inexpensive, and abundant source of cardiomyocytes. Moreover, in some instances, the cardiomyocytes of the invention can be modified such that rejection of the cardiomyocytes upon introduction into a xenogeneic recipient is inhibited, thereby eliminating the requirement for generalized suppression of the immune system. Web site: http://www.delphion.com/details?pn=US06491912__ •

Receptor specific atrial natriuretic peptides Inventor(s): Burnier; John P. (Pacifica, CA), Cunningham; Brian C. (Piedmont, CA), Lowe; David G. (Brisbane, CA), McDowell; Robert S. (San Francisco, CA), Oare; David (Belmont, CA) Assignee(s): Genentech, Inc. (South San Francisco, CA) Patent Number: 6,525,022 Date filed: September 16, 1998 Abstract: Human receptor selective atrial natriuretic factor variants containing various substitutions, especially G16R, show equal potency and binding affinity for the human A-receptor but have decreased affinity for the human clearance or C-receptor. These ANF variants have natriuretic, diuretic and vasorelaxant activity but have increased metabolic stability, making them suitable for treating congestive heart failure, acute kidney failure and renal hypertension. Excerpt(s): The invention relates to synthetic peptides having diuretic, natriuretic, and/or vasodilatory activity in mammals. The peptides of this invention are related to atrial natriuretic peptide (ANP) but exhibit decreased binding affinity to the natriuretic peptide clearance receptor (NPR-C) and improved stability toward peptidases ("enkephalinase") known to hydrolyze natriuretic peptides. Maintenance of normal extracellular fluid volume depends primarily on the excretion of sodium (natriuresis) and water (diuresis) by the kidneys. These are, in turn, primarily determined by (1) the rate at which plasma is filtered at the glomerulus (glomerular filtration rate, or GFR) and (2) the degree to which sodium is actively reabsorbed along the renal tubule (with water presumably following passively). Sodium reabsorbtion is regulated, in part, by the adrenal steroid hormone aldosterone, in part by blood pressure, hematocrit and plasma viscosity and in part by various atrial natriuretic factors (ANF's) or hormones (deBold, A. J. et al., Life Sciences 28:89-94 [1981]; Garcia R., Experientia 38:1071-73 [1982]; Currie, M. S. et al. Science 221:71-73 [1983]; Flynn T. G. et al., Biochem. Biophys. Res. Commun. 117:859-865 [1983]; Currie, M. G. et al., Science 223:67-69 [1984]; and Kanagawa, K. et al., Biochem. Biophys. Res. Commun. 118:131-139 [1984]). Atrial natriuretic factors are released as a result of sensors in the atrium responsible for detecting extracellular fluid volume. It is believed that an increase in extracellular fluid volume is detected by these sensors as the atrium stretches to accommodate the increased venous return volume. In response to this stimulus ANF is released into the blood stream where it is transported to the kidney. Binding of ANF to a specific natriuretic peptide receptor (hNPR-A) in the kidney causes inhibition of sodium reabsorbtion along the renal tubule decreasing the reabsorption of water and lowering the extracellular fluid volume. Web site: http://www.delphion.com/details?pn=US06525022__

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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 (-) 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__

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System and method for automatically verifying capture during multi-chamber stimulation Inventor(s): Bornzin; Gene A. (Simi Valley, CA), Bradley; Kerry (Glendale, CA), Florio; Joseph J. (La Canada, CA), Park; Euljoon (Stevenson Ranch, CA) Assignee(s): Pacesetter, Inc. (Sylmar, CA) Patent Number: 6,512,953 Date filed: April 26, 2001 Abstract: A system and corresponding method are provided to reliably detect capture during multi-chamber stimulation, and to further monitor the progression of congestive heart failure. The system provides a method by which intracardiac electrogram (IEGM) characteristics representing single-chamber capture and bi-ventricular capture are stored in memory and displayed. The annotation of the displayed waveforms is such that events associated with loss of capture, single-chamber capture, and bi-ventricular capture are clearly marked for ready interpretation by the physician. In a first situation, a stimulation pulse is followed by a time delay window and a subsequent depolarization complex that represents intrinsic responses of the chambers that have not been captured. In a second situation, a stimulation pulse is followed almost immediately by an evoked response that represents capture of one chamber, and a subsequent depolarization complex that represents an intrinsic response of one chamber that has not

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been captured. In a third situation, a stimulation pulse is almost immediately followed by an evoked response that represents simultaneous capture of two chambers. Excerpt(s): This invention relates generally to a programmable cardiac stimulating apparatus for the purpose of automatically verifying capture during multi-chamber stimulation. More specifically, the present invention is directed to an implantable stimulation device and associated method for automatically verifying simultaneous capture during bi-ventricular or bi-atrial stimulation, also referred to herein as bichamber stimulation or two corresponding chamber stimulation. 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 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. Web site: http://www.delphion.com/details?pn=US06512953__ •

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, endstage 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

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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 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 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__

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Patent Applications on Congestive Heart Failure As of December 2000, U.S. patent applications are open to public viewing.10 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to congestive heart failure: •

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 alphaadrenergic 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

10

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

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Allenic aryl sulfonamide hydroxamic acids as matrix metalloproteinase and tace inhibitors Inventor(s): Delos Santos, Efren Guillermo; (Nanuet, NY), Sandanayaka, Vincent Premaratna; (Northboro, MA) Correspondence: Daniel B. Moran; Five Giralda Farms; Madison; NJ; 07940; US Patent Application Number: 20030130238 Date filed: November 1, 2002 Abstract: Compounds of the formula 1are useful in treating disease conditions mediated by TNF-.alpha., such as rheumatoid arthritis, osteoarthritis, sepsis, AIDS, ulcerative colitis, multiple sclerosis, Crohn's disease, degenerative cartilage loss, graft rejection, cachexia, inflammation, fever, insulin resistance, septic shock, congestive heart failure, inflammatory disease of the central nervous system, inflammatory bowel disease and HIV. Excerpt(s): This invention relates to allenic aryl sulfonamide hydroxamic acids which act as inhibitors of TNF-.alpha. converting enzyme (TACE) and matrix metalloproteinase (MMP). The compounds of the present invention are useful in disease conditions mediated by MMP and TACE, such as rheumatoid arthritis, osteoarthritis, sepsis, AIDS, ulcerative colitis, multiple sclerosis, Crohn's disease, degenerative cartilage loss, graft rejection, cachexia, inflammation, fever, insulin resistance, septic shock, congestive heart failure, inflammatory disease of the central nervous system, inflammatory bowel disease and HIV. TNF-.alpha. converting enzyme (TACE) catalyzes the formation of TNF-.alpha. from membrane bound TNF-.alpha. precursor protein. TNF-.alpha. is a proinflammatory cytokine that is believed to have a role in rheumatoid arthritis [Shire, M. G.; Muller, G. W. Exp. Opin. Ther. Patents 1998, 8(5), 531; Grossman, J. M.; Brahn, E. J. Women's Health 1997, 6(6), 627; Isomaki, P.; Punnonen, J. Ann. Med. 1997, 29, 499; Camussi, G.; Lupia, E. Drugs, 1998, 55(5), 613.] septic shock [Mathison, et. al. J. Clin. Invest. 1988, 81, 1925; Miethke, et. al. J. Exp. Med. 1992, 175, 91.], graft rejection [Piguet, P. F.; Grau, G. E.; et. al. J. Exp. Med. 1987, 166, 1280.], cachexia [Beutler, B.; Cerami, A. Ann. Rev. Biochem. 1988, 57, 505.], anorexia, inflammation [Ksontini, R,; MacKay, S. L. D.; Moldawer, L. L. Arch. Surg. 1998, 133, 558.], congestive heart failure [Packer, M. Circulation, 1995, 92(6), 1379; Ferrari, R.; Bachetti, T.; et. al. Circulation, 1995, 92(6), 1479.], post-ischaemic reperfusion injury, inflammatory disease of the central nervous system, inflammatory bowel disease, insulin resistance [Hotamisligil, G. S.; Shargill, N. S.; Spiegelman, B. M.; et. al. Science, 1993, 259, 87.] and HIV infection [Peterson, P. K.; Gekker, G.; et. al. J. Clin. Invest. 1992, 89, 574; Pallares-Trujillo, J.; Lopez-Soriano, F. J. Argiles, J. M. Med. Res. Reviews, 1995, 15(6), 533.]], in addition to its well-documented antitumor properties [Old, L. Science, 1985, 230, 630.]. For example, research with antiTNF-.alpha. antibodies and transgenic animals has demonstrated that blocking the formation of TNF-.alpha. inhibits the progression of arthritis [Rankin, E. C.; Choy, E. H.; Kassimos, D.; Kingsley, G. H.; Sopwith, A. M.; Isenberg, D. A.; Panayi, G. S. Br. J. Rheumatol. 1995, 34, 334; Pharmaprojects, 1996, Therapeutic Updates 17 (Oct.), au197M2Z.]. This observation has recently been extended to humans as well as described in "TNF-.alpha. in Human Diseases", Current Pharmaceutical Design, 1996, 2, 662. Matrix metalloproteinases (MMPs) are a group of enzymes that have been implicated in the pathological destruction of connective tissue and basement membranes. These zinc containing endopeptidases consist of several subsets of enzymes including collagenases, stromelysins and gelatinases. Of these classes, the gelatinases have been shown to be the MMPs most intimately involved with the growth and spread of tumors. It is known that the level of expression of gelatinase is elevated in malignancies, and that gelatinase can

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degrade the basement membrane which leads to tumor metastasis. Angiogenesis, required for the growth of solid tumors, has also recently been shown to have a gelatinase component to its pathology. Furthermore, there is evidence to suggest that gelatinase is involved in plaque rupture associated with atherosclerosis. Other conditions mediated by MMPs are restenosis, MMP-mediated osteopenias, inflammatory diseases of the central nervous system, skin aging, tumor growth, osteoarthritis, rheumatoid arthritis, septic arthritis, corneal ulceration, abnormal wound healing, bone disease, proteinuria, aneurysmal aortic disease, degenerative cartilage loss following traumatic joint injury, demyelinating diseases of the nervous system, cirrhosis of the liver, glomerular disease of the kidney, premature rupture of fetal membranes, inflammatory bowel disease, periodontal disease, age related macular degeneration, diabetic retinopathy, proliferative vitreoretinopathy, retinopathy of prematurity, ocular inflammation, keratoconus, Sjogren's syndrome, myopia, ocular tumors, ocular angiogenesis/neo-vascularization and corneal graft rejection. For recent reviews, see: (1) Recent Advances in Matrix Metalloproteinase Inhibitor Research, R. P. Beckett, A. H. Davidson, A. H. Drummond, P. Huxley and M. Whittaker, Research Focus, Vol. 1,16-26, (1996), (2) Curr. Opin. Ther. Patents (1994) 4(1): 7-16, (3) Curr. Medicinal Chem. (1995) 2: 743-762, (4) Exp. Opin. Ther. Patents (1995) 5(2): 1087-110, (5) Exp. Opin. Ther. Patents (1995) 5(12): 1287-1196: (6) Exp. Opin. Ther. Patents (1998) 8(3): 281-259. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Cardiac rhythm management system with maximum tracking rate (MTR) hysteresis Inventor(s): Kramer, Andrew P.; (Stillwater, MN) Correspondence: Schwegman, Lundberg, Woessner & Kluth, P.A.; P.O. Box 2938; Minneapolis; MN; 55402; US Patent Application Number: 20030088287 Date filed: November 6, 2001 Abstract: A cardiac rhythm management system provides both a safe maximum pacing rate limit and a physiological maximum pacing rate limit. The present subject matter provides a solution to problems associated with the use of a single maximum tracking rate (MTR). In one embodiment, the present subject matter utilizes two MTRs, where the first is a normal MTR and the second is a hysteresis MTR. In one embodiment, the hysteresis MTR is set higher than the normal MTR. The hysteresis MTR functions as a maximum pacing rate limit while tracking an atrial rate until the atrial rate exceeds the hysteresis MTR limit. When the atrial rate exceeds the hysteresis MTR limit, the maximum pacing rate limit is set to the normal MTR. Once the atrial rate falls below a predetermined threshold, the maximum pacing rate limit is set to the hysteresis MTR. The predetermined threshold may be set to the normal MTR, the hysteresis MTR, or other rates. In one embodiment, changing the maximum pacing rate limit in this fashion allows for uninterrupted pacing treatment for patients, such as congestive heart failure (CHF) patients, who may display fast but physiologically normal heart rates and need cardiac resynchronization therapy (CRT) at such fast heart rates. Such a pacing treatment provides for a more rapid and natural maximum pacing rate limit for the patient, while still protecting the patient from being paced at abnormally high rates. Excerpt(s): The present invention relates generally to cardiac rhythm management devices, and more particularly, but not by way of limitation, to a cardiac rhythm management system with maximum pacing rate hysteresis. When functioning properly, the human heart maintains its own intrinsic rhythm, and is capable of pumping

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adequate blood throughout the body's circulatory system. However, some people have abnormal cardiac electrical conduction patterns and irregular cardiac rhythms that are referred to as cardiac arrhythmias. Such arrhythmias result in diminished blood circulation. One mode of treatment includes use of a cardiac rhythm management system. Such systems are often implanted in a patient and deliver electrical stimulation therapy to the patient's heart. Cardiac rhythm management systems include, among other things, pacemakers, also referred to as pacers. Pacemakers deliver timed sequences of low energy electrical stimuli, called pacing pulses, to the heart, typically via one or more intravascular leadwires or catheters (referred to as "leads") each having one or more electrodes disposed in or about the heart. Heart contractions are initiated in response to such pacing pulses (this is referred to as "capturing" the heart). Pacemakers also sense electrical activity of the heart in order to detect depolarization signals corresponding to the electrical excitation associated with heart contractions. This function is referred to as cardiac sensing. Cardiac sensing is used to time the delivery of pacing pulses with the heart's intrinsic (native) rhythm. By properly timing the delivery of pacing pulses, the heart can be induced to contract in a proper rhythm, greatly improving its output of blood. Pacemakers are often used to treat patients with bradyarrhythmias (also referred to as bradycardias), that is, hearts that beat too slowly. For that application, the pacemakers may operate in an "on-demand" mode, such that a pacing pulse is delivered to the heart only in absence of a normally timed intrinsic contraction. The on-demand pacing function is often embodied in algorithms exhibiting pace inhibition, in which pacing in a lead is prevented (inhibited) for one heart beat when a cardiac depolarization is detected in the same lead prior to the pace. In bradycardia patients, for example, on-demand pacing can ensure that pacing pulses are delivered only when the patient's intrinsic heart rate drops below a predetermined minimum pacing rate limit, referred to as a lower rate limit (LRL). Some pacemakers provide for two lower rate limits, a first LRL, sometimes called a normal LRL, to provide a minimum necessary heart rate during awake or exercise periods, and a second LRL, sometimes called a hysteresis LRL, to allow the heart to reach naturally slower rates during sleep. When the patent's heart rate falls below the hysteresis LRL, the pacemaker switches to the normal LRL to ensure the patient will have sufficient cardiac output by protecting the patient against abnormally slow heart rates. 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

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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 •

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: 20030114469 Date filed: August 28, 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; anda 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): a pharmaceutically acceptable carrier. Anti-diabetic agents include insulin secretion enhancers which are active ingredients that have the property to promote the secretion of insulin from pancreatic.beta.-cells. Examples of insulin secretion enhancers are a biguanide derivative, for example, metformin or, if appropriate, a pharmaceutically acceptable salt thereof, especially the hydrochloride thereof. Other

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insulin secretion enhancers include sulfonylureas (SU), especially those which promote the secretion of insulin from pancreatic.beta.-cells by transmitting signals of insulin secretion via SU receptors in the cell membrane including, but are not limited to, tolbutamide; chlorpropamide; tolazamide; acetohexamide; 4-chloro-N-[(1pyrolidinylamino)carbonyl]-benzensulfonamide (glycopyramide); glibenclamide (glyburide); gliclazide; 1-butyl-3-metanilylurea; carbutamide; glibonuride; glipizide; gliquidone; glisoxepid; glybuthiazole; glibuzole; glyhexamide; glymidine; glypinamide; phenbutamide; and tolylcyclamide, or pharmaceutically acceptable salts thereof. and repaglinide [(S)-2-ethoxy-4-{2-[[3-methyl-1-[2-(1-piperidinyl)p- henyl]butyl]amino]-2oxoethyl}benzoic acid]. Repaglinide is disclosed in EP 589874, EP 147850 A2, in particular Example 11 on page 61, and EP 207331 A1. It can be administered in the form as it is marketed, e.g., under the trademark NovoNorm.TM.; calcium (2S)-2-benzyl-3(cis-hexahydro-- 2-isoindolinlycarbonyl)-propionate dihydrate (mitiglinide--cf. EP 507534); furthermore representatives of the new generation of SUs such as glimepiride (cf. EP 31058); in free or pharmaceutically acceptable salt form. The term nateglinide likewise comprises crystal modifications such as disclosed in EP 0526171 B1 or U.S. Pat. No. 5,488,510, respectively, the subject matter of which, especially with respect to the identification, manufacture and characterization of crystal modifications, is herewith incorporated by reference to this application, especially the subject matter of claims 8-10 of said U.S. patent (referring to H-form crystal modification) as well as the corresponding references to the B-type crystal modification in EP 196222 B1 the subject matter of which, especially with respect to the identification, manufacture and characterization of the B-form crystal modification. Preferably, in the present invention, the B- or H-type, more preferably the H-type, is used. Nateglinide can be administered in the form as it is marketed, e.g., under the trademark STARLIX.TM. 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

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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, 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 •

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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Growth hormone secretagogues Inventor(s): Carpino, Philip A.; (Groton, CT) Correspondence: Pfizer INC.; Patent Department, Ms8260-1611; Eastern Point Road; Groton; CT; 06340; US Patent Application Number: 20030130284 Date filed: December 6, 2002 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, 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, maintanence of skin thickness, metabolic homeostasis or renal homeostasis. The compounds of the present invention are also useful in treating osteoporosis when used in combination with: a bisphosphonate compound such as alendronate; estrogen, premarin, and optionally progesterone; a.beta.sub.3 adrenergic receptor agonist; 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. Excerpt(s): This invention relates to dipeptide compounds, which are growth hormone secretagogues and are useful for the treatment and prevention of musculoskeletal frailty including osteoporosis. 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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Immunoassays for human and canine brain natriuretic peptide Inventor(s): Lewicki, John; (San Jose, CA), Porter, J. Gordon; (Newark, CA), Scarborough, Robert M.; (Hayward, CA), Seilhamer, J. Jeffrey; (Milpitas, CA) Correspondence: Morrison & Foerster Llp; 3811 Valley Centre Drive; Suite 500; San Diego; CA; 92130-2332; US Patent Application Number: 20030109430 Date filed: July 9, 2001

184 Congestive Heart Failure

Abstract: The cDNA sequence encoding porcine brain natriuretic peptide and related genes encoding canine and human peptides with natriuretic activity are disclosed. The gene is shown to make accessible the DNAs encoding analogous natriuretic peptides in other vertebrate species. The genes encoding these NPs can be used to effect modifications of the sequence to produce alternate forms of the NPs and to provide practical amounts of these proteins. The NPs of the invention can also be synthesized chemically. The invention peptides have the formula: 1 R.sup.1-Cys-Phe-Gly-Arg-Arg/Leu/-Asp-Arg- Lys Met (1) Ile-Gly/-Ser-Leu/-Ser-Gly-Leu-Gly-Cys-R.- sup.2 Ser Serwherein R.sup.1 is selected from the group consisting of: 2 (H); Gly-; Ser-Gly-; Asp/ Lys/ -Ser-Gly-; Gly Arg/ Asp/ His/ - Lys/ -Ser-Gly-; Gln Gly Arg/ Asp/ Met/ - His/ Lys/ -Ser-Gly-; Val Gln Gly Arg/ Asp/ Thr/ - Met/ - His/ - Lys/ -Ser-Gly-; Met Val Gln Gly Arg/ Asp/ Lys- Thr/ - Met/ - His/ - Lys/ -Ser-Gly-; Met Val Gln Gly Arg/ Asp/ Pro-Lys- Thr/ - Met/ - His/ - Lys/ -Ser-Gly-; Met Val Gln Gly Arg/ Asp/ SerPro-Lys- Thr/ - Met/ - His/ - Lys/ -Ser-Gly-; Met Val Gln Glyor a 10- to 109-amino acid sequence shown as the native upstream sequence for porcine, canine or human BNP in FIG. 8, or a composite thereof;R.sup.2 is (OH), NH.sub.2, or NR'R" wherein R' and R" are independently lower alkyl (1-4C) or is 3 Asn/ Lys Asn/ -Val Lys Asn/ -Val-Leu Lys Asn/ -Val-Leu-Arg Lys Asn/ -Val-Leu-Arg- Arg/ Lys Lys Asn/ -Val-Leu-Arg- Arg/ Tyr/ Lys Lys Hisor the amides (NH.sub.2 or NR'R") thereof, with the proviso that if formula (1) is 4 R.sup.1-Cys-Phe-Gly-Arg-Arg-Leu-Asp-Arg- Ile-Gly-Ser-Leu-Ser-GlyLeu-Gly-Cys-R.sup.2and R.sup.1 is Asp-Ser-Gly-, R.sup.2 cannot be Asn-Val-Leu-ArgArg-Tyr.The peptides of the invention can be formulated into pharmaceutical compositions and used to treat conditions associated with high extracellular fluid levels, especially congestive heart failure. Excerpt(s): This is a continuation-in-part of U.S. Ser. No. 206,470, filed Jun. 14, 1988, which is a continuation-in-part of U.S. Ser. No. 200,383, filed May 31, 1988. The invention relates generally to natriuretic and homologous peptides found in brain and cardiac tissue. More particularly, it relates to the gene encoding a natriuretic peptide obtained from porcine brain and genes encoding peptides related by amino acid sequence in other species. The existence of peptides in the atrium which are responsible for maintenance of normal extracellular fluid parameters--i.e., the volume and pressure of liquid in the blood vessels--is well known. A series of closely related peptides, designated atrial natriuretic peptides, have been isolated from several species and identified, and analogs of these peptides have been prepared. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

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.

Patents 185

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 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 •

Implantable heart assist system and method of applying same Inventor(s): Bolling, Steven F.; (Ann Arbor, MI), Charhut, Ken; (Lake Forest, CA) Correspondence: Knobbe Martens Olson & Bear Llp; 2040 Main Street; Fourteenth Floor; Irvine; CA; 91614; US Patent Application Number: 20030088147 Date filed: June 11, 2002 Abstract: A method for further reducing the load on a heart suffering (ventricular size maintenance) from congestive heart failure comprising the application of a subcardiac pump having inflow and outflow conduits configured to fluidly connect to non-primary vessels in such a manner as to reduce the load on and/or the size of the heart prior to applying a device intended to reduce the stress on a wall of the ailing heart. Excerpt(s): This application is a continuation-in-part of U.S. Application Ser. No. 10/078,260, filed on Feb. 15, 2002, which is a continuation-in-part of U.S. application Ser. No. 09/552,979, filed on Apr. 21, 2000, now U.S. Pat. No. 6,390,969, which is a continuation-in-part of U.S. application Ser. No. 09/470,841, filed on Dec. 23, 1999, now U.S. Pat. No. 6,387,037, which is a continuation-in-part of U.S. application Ser. No. 09/289,231, filed on Apr. 9, 1999, which is continuation-in-part of U.S. application Ser. No. 09/166,005, filed on Oct. 2, 1998, now U.S. Pat. No. 6,200,260, which claims the benefit of U.S. Provisional Application Serial No. 60/061,434, filed Oct. 9, 1997, all of which are incorporated herein in their entirety by reference. The present invention relates generally to a system for assisting the heart and, in particular, to an extracardiac pumping system and a method for both supplementing the circulation of blood through the patient and for enhancing vascular blood mixing using a minimally invasive procedure. During the last decade, congestive heart failure (CHF) has burgeoned into the most important public health problem in cardiovascular medicine. As reported in Gilum, R. F., Epidemiology of Heart Failure in the U.S., 126 Am. Heart J. 1042 (1993), four hundred thousand (400,000) new cases of CHF are diagnosed in the United States annually. The disorder is said to affect nearly 5 million people in this country and close to 20 million people worldwide. The number of hospitalizations for CHF has increased more than three fold in the last 15 years. Unfortunately, nearly 250,000 patients die of heart failure annually. According to the Framingham Heart Study, the 5-year mortality rate for patients with congestive heart failure was 75 per cent in men and 62 per cent in women (Ho, K. K. L., Anderson, K. M., Kannel, W. B., et al., Survival After the Onset of

186 Congestive Heart Failure

Congestive Heart Failure in Framingham Heart Study Subject, 88 Circulation 107 (1993)). This disorder represents the most common discharge diagnosis for patients over 65 years of age. Although the incidence of most cardiovascular disorders has decreased over the past 10 to 20 years, the incidence and prevalence of congestive heart failure has increased at a dramatic rate. This number will increase as patients who would normally die of an acute myocardial infarction (heart attack) survive, and as the population ages. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Indole carboxylic acids as thyroid receptor ligands Inventor(s): Aspnes, Gary E.; (Rockville, RI), Chiang, Yuan-Ching P.; (East Lyme, CT) Correspondence: Pfizer INC.; Patent Department, Ms8260-1611; Eastern Point Road; Groton; CT; 06340; US Patent Application Number: 20030078289 Date filed: September 24, 2002 Abstract: A compound of the formula 1wherein W, R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8 and R.sup.13 are as defined herein, useful in the treatment of obesity, overweight condition, hyperlipidemia, glaucoma, cardiac arrhythmias, skin disorders, thyroid disease, hypothyroidism, thyroid cancer and related disorders and diseases such as diabetes mellitus, atherosclerosis, hypertension, coronary heart disease, congestive heart failure, hypercholesteremia, depression, osteoporosis and hair loss. Excerpt(s): This non-provisional application claims the benefit of U.S. provisional application No. 60/325,385, filed Sep. 26, 2001. The present invention relates to novel thyroid receptor ligands and, more preferably, relates to indole carboxylic acids, and derivatives thereof, which are useful in the treatment of obesity, overweight condition, hyperlipidemia, glaucoma, cardiac arrhythmias, skin disorders, thyroid disease, hypothyroidism, thyroid cancer and related disorders and diseases such as diabetes mellitus, atherosclerosis, hypertension, coronary heart disease, congestive heart failure, hypercholesteremia, depression, osteoporosis and hair loss. The present invention also provides methods, pharmaceutical compositions and kits for treating such diseases and disorders. Thyroid hormones are important in normal development and in maintaining metabolic homeostasis. For example, thyroid hormones stimulate the metabolism of cholesterol to bile acids and enhance the lipolytic responses of fat cells to other hormones. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Isoindole-imide compounds, compositions, and uses thereof Inventor(s): Chen, Roger Shen-Chu; (Edison, NJ), Man, Hon-Wah; (Princeton, NJ), Muller, George W.; (Bridgewater, NJ), Robarge, Michael J.; (North Plainfield, NJ) Correspondence: Pennie And Edmonds; 1155 Avenue OF The Americas; New York; NY; 100362711 Patent Application Number: 20030096841 Date filed: December 21, 2001

Patents 187

Abstract: The invention relates to isoindole-imide compounds and pharmaceutically acceptable salts, hydrates, solvates, clathrates, enantiomers, diastereomers, racemates, or mixtures of stereoisomers thereof, pharmaceutical compositions comprising these isoindole-imide compounds, and methods for reducing the level of cytokines and their precursors in mammals. In particular, the invention pertains to isoindole-imide compounds that are potent inhibitors of the production of TNF-.alpha. in mammals. The isoindole-imides described herein are useful for treating or preventing diseases or disorders in mammals, for example, cancers, such as solid tumors and blood-born tumors; heart disease, such as congestive heart failure; osteoporosis; and genetic, inflammatory; allergic; and autoimmune diseases. Excerpt(s): This application is a continuation-in-part of U.S. application Ser. No. 09/972,487 filed Oct. 5, 2001, which claims the benefit of U.S. Provisional Application No. 60/258,372, filed Dec. 27, 2000, and which applications are hereby expressly incorporated by reference herein. The invention encompasses novel compounds including compounds having an isoindole-imide moiety, pharmaceutically acceptable salts, hydrates, solvates, clathrates, enantiomers, diastereomers, racemates, or mixtures of stereoisomers thereof, pharmaceutical compositions of these compounds, and methods of using these compounds and compositions in mammals for treatment or prevention of diseases. The present invention relates to isoindole-imide compounds and pharmaceutically acceptable salts, hydrates, solvate, clathrate, enantiomer, diastereomer, racemate, or mixture of stereoisomers thereof; pharmaceutical compositions comprising these isoindole-imide compounds; and methods for reducing the level of cytokines and their precursors in mammals. In particular, the invention includes isoindole-imide compounds that have one or more of the following activities: modulation of the production of TNF-.alpha.; modulation of the production of IL1.beta.; stimulation of the production of IL-10, or stimulation of the production T-cells. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Method and apparatus for providing positive airway pressure to a patient Inventor(s): Estes, Mark C.; (Sylmar, CA), Fiore, John; (Monroeville, PA), Kepler, Jeff; (Pittsburgh, PA), Mechlenburg, Douglas M.; (Murrysville, PA), Ressler, Heather; (New Alexandria, PA) Correspondence: Michael W. Haas, Intellectual Property Counsel; Respironics, INC.; 1010 Murry Ridge Lane; Murrysville; PA; 15668; US Patent Application Number: 20030121519 Date filed: November 26, 2002 Abstract: A system including methods and apparatus for treatment of a medical disorder such as obstructive sleep apnea or congestive heart failure. The system involves applying a gain to flow rate of pressurized gas delivered to a patient during inspiratory and/or expiratory phases of a respiratory cycle to deliver the pressurized gas in proportion to the respective gains during inspiration and/or 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 treatments, such as CPAP or bi-level positive airway pressure equipment to effect various beneficial treatment applications.

188 Congestive Heart Failure

Excerpt(s): This is a continuation-in-part of U.S. patent application Ser. No. 09/610,733 filed Jul. 6, 2000, which is a continuation of U.S. patent application Ser. No. 09/041,195 filed Mar. 12, 1998, now U.S. Pat. No. 6,105,575, which is a continuation-in-part of U.S. patent application Ser. No. 08/679,898 filed Jul. 15, 1996, which is a continuation-in-part of application Ser. No. 08/253,496 filed Jun. 3, 1994, now U.S. Pat. No. 5,535,738. 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. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Method and devices for decreasing elevated pulmonary venous pressure Inventor(s): Shaknovich, Alexander; (New York, NY) Correspondence: Knobbe Martens Olson & Bear Llp; 2040 Main Street; Fourteenth Floor; Irvine; CA; 92614; US Patent Application Number: 20030191527 Date filed: May 15, 2003 Abstract: 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 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-dimension non-expandable pulmonary vein prosthetic valves for implantation by a variety of surgical and percutaneous procedures are also described. Excerpt(s): This application claims priority to U.S. Provisional Application No. 60/228,574, filed Aug. 29, 2000. 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 fixed-dimension 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

Patents 189

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. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Method and system for the transitional care of congestive heart failure patients Inventor(s): Kowalski, Debra; (Troy, MI), Voytas, John; (Waterford, MI) Correspondence: Harness, Dickey & Pierce, P.L.C.; P.O. Box 828; Bloomfield Hills; MI; 48303; US Patent Application Number: 20030083904 Date filed: September 10, 2002 Abstract: A method for the transitional care of patients, including but not limited to congestive heart failure patients, includes the step of conducting a hospital consultation prior to a discharge from an extended hospital stay. When a patient is identified as being a proper candidate for a transitional care facility, the patient is discharged to the transitional care facility. At the transitional care facility, the patient is repeatedly educated regarding topics selected from the group of warning signs, medication, diet and exercise. The patient is tested for a level knowledge regarding the one or more topics. A transitional care facility consultation is conducted to determine whether the patient is a proper candidate for discharge to home care. In such event, the patient is discharged to home care and a summary is generated to a referring physician of the patient regarding a recommendation for continued care. Excerpt(s): This application is based on provisional patent application which has been assigned U.S. Serial No. 60/318,640, filed Sep. 10, 2001. The present invention generally relates to patient care. More particularly, the present invention relates to a method and system for the transitional care of patients discharged from a hospital. In one particular application, the present invention relates to a method and system for the transitional care of congestive heart failure patients which should significantly reduce the incidence of early hospital readmittance. Before a patient is discharged from an extended hospital stay, discharge instructions are conventionally provided that detail such items as continuing medication, exercise and diet. These instructions are not always sufficiently followed by the discharged patient. This is particularly true for geriatric patients whom often require more time to comprehend detailed instructions and in addition often become deconditioned while bedfast in the hospital. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

190 Congestive Heart Failure

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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.

Patents 191

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 treatment for decreasing mortality resulting from congestive heart failure Inventor(s): Lukas-Laskey, Mary Ann; (Philadelphia, PA), Ruffolo, Robert JR.; (Spring City, PA), Shusterman, Neil Howard; (Wynnewood, PA), Sponer, Gisbert; (Laudenbach, DE), Strein, Klaus; (Hemsbach, DE) Correspondence: Glaxosmithkline; Corporate Intellectual Property - Uw2220; P.O. Box 1539; King OF Prussia; PA; 19406-0939; US Patent Application Number: 20030105138 Date filed: December 19, 2002 Abstract: A method of treatment using a compound of Formula I: 1wherein:R.sub.1 is hydrogen, lower alkanoyl of up to 6 carbon atoms or aroyl selected from benzoyl and naphthoyl;R.sub.2 is hydrogen, lower alkyl of up to 6 carbon atoms or arylalkyl selected from benzyl, phenylethyl and phenylpropyl;R.sub.3 is hydrogen or lower alkyl of up to 6 carbon atoms;R.sub.4 is hydrogen or lower alkyl of up to 6 carbon atoms, or when X is oxygen, R.sub.4 together with R.sub.5 can represent --CH.sub.2--0--;X is a valency bond, --CH.sub.2, oxygen or sulfur;Ar is selected from phenyl, naphthyl, indanyl and tetrahydronaphthyl;R.sub.5 and R.sub.6 are individually selected from hydrogen, fluorine, chlorine, bromine, hydroxyl, lower alkyl of up to 6 carbon atoms, a -CONH.sub.2-- group, lower alkoxy of up to 6 carbon atoms, benzyloxy, lower alkylthio of up to 6 carbon atoms, lower alkysulphinyl of up to 6 carbon atoms and lower alkylsulphonyl of up to 6 carbon atoms; orR.sub.5 and R.sub.6 together represent methylenedioxy;or a pharmaceutically acceptable salt thereof, alone or in conjunction with one or more other therapeutic agents, said agents being selected from the group consisting of ACE inhibitors, diuretics, and digoxin for decreasing mortality resulting from congestive heart failure (CHF) in mammals, particularly humans. Excerpt(s): The present invention relates to a new method of treatment using compounds which are dual non-selective.beta.-adrenoceptor and.alpha.sub.1adrenoceptor antagonists, in particular the carbazolyl-(4)-oxypropanolamine compounds of Formula I, preferably carvedilol, for decreasing the mortality of patients suffering from congestive heart failure (CHF). The invention also relates to a method of treatment using compounds which are dual non-selective.beta.-adrenoceptor and.alpha.sub.1-adrenoceptor antagonists, in particular the carbazolyl-(4)oxypropanolamine compounds of Formula I, preferably carvedilol, in conjunction with one or more other therapeutic agents, said agents being selected from the group consisting of angiotensin converting enzyme (ACE) inhibitors, diuretics, and digoxin, for decreasing the mortality of patients suffering from CHF. Congestive heart failure occurs as a result of impaired pumping capability of the heart and is associated with abnormal retention of water and sodium. Traditionally, treatment of chronic mild failure has included limitation of physical activity, restriction of salt intake, and the use of a diuretic. If these measures are not sufficient, digoxin, which is an agent that increases the force of mycardial contraction, is typically added to the treatment regiment.

192 Congestive Heart Failure

Subsequently, angiotensin converting enzyme inhibitors, which are compounds that prevent the conversion of angiotensin I into the pressor-active angiotensin II, are prescribed for chronic treatment of congestive heart failure, in conjunction with a diuretic, digoxin, or both. Congestive heart failure is a condition that is associated with activation of both the renin-angiotensin system (RAS) and the sympathetic nervous system (SNS). Modulation of the RAS by angiotensin converting enzyme inhibitors has been shown to improve the symptoms associated with CHF. Sharpe, D. N., Murphy, J., Coxon, R. & Hannan S. F. (1984) Circulation, 70, 271-278. However, ACE inhibitors appear to have little effect on the enhanced SNS in CHF. Cohn, J. N., Johnson, G. & Ziesche, S., (1991) N. Engl. J. Med., 325, 293-302 and Francis, G. S., Rector, T. S. & Cohn, J. N. (1988) Am. Heart J., 116, 1464-1468. Therefore, there is a need for an agent that would be effective in blocking the activation of the SNS in CHF patients. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

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 and compositions for use of (S)-bisoprolol Inventor(s): Devane, John; (Athlone, IE), Kelly, John; (Drumcondra, IE) Correspondence: Finnegan, Henderson, Farabow; Garrett & Dunner, L.L.P.; 1300 I Street, N.W.; Washington; DC; 20005-3315; US Patent Application Number: 20030091633 Date filed: August 22, 2002 Abstract: Methods of treating, preventing, and/or managing cardiovascular conditions such as hypertension, ischemic heart disease, atrial fibrillation, congestive heart failure, angina pectoris, and cardiac arrhythmias, with the (S) stereoisomer of bisoprolol are disclosed, as are compositions and formulations comprising (S)-bisoprolol.

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Excerpt(s): This application claims priority to U.S. Provisional Patent Application No. 60/335,884, filed Nov. 15, 2001, the entire disclosure of which is incorporated herein by reference. Bisoprolol (1-[4-[[2-(1-methylethoxy)ethoxy]-methyl]phenoxy]-3-[(1-methylethyl)amino]-2-propanol), in its racemic form, is a commercially available drug that acts as a.beta.-adrenergic blocking agent (antagonist). The drug acts by blocking neurotransmitter action at.beta.-adrenergic receptors and, as a consequence, disrupts sympathetic nervous system transmission. The effects of.beta.-adrenergic blockade are widespread, reflecting the distribution of these receptors throughout the body. They include, but are not limited to, effects on the heart and cardiovascular system, the gastrointestinal tract, the respiratory tract, the eye, the liver, and the genitourinary system. These effects and others are described, for example, in textbooks such as Goodman and Gilman's. The Pharmacological Basis of Therapeutics (McGraw Hill, 1996) and Rang, Dale and Ritter's Pharmacology (Churchill Livingstone, 1999). The.beta.-adrenergic antagonists are indicated for a number of conditions including, but not limited to, hypertension, ischemic heart disease, atrial fibrillation, congestive heart failure, peripheral arterial occlusive disease, angina pectoris, cardiac dysrhythmias, heart failure, glaucoma, migraine, the effects of thyroid disease, and symptoms of anxiety, such as palpitations. The antagonists are most commonly used in treatment of diseases of the cardiovascular system. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Methods of treatment and pharmaceutical composition Inventor(s): Ksander, Gary Michael; (Amherst, NH), Webb, Randy Lee; (Flemington, NJ) Correspondence: Thomas Hoxie; Novartis, Corporate Intellectual Property; One Health Plaza 430/2; East Hanover; NJ; 07936-1080; US Patent Application Number: 20030144215 Date filed: January 14, 2003 Abstract: The invention relates a pharmaceutical composition comprising a combination of:(i) the AT 1-antagonist valsartan or a pharmaceutically acceptable salt thereof; and(ii) a NEP inhibitor or a pharmaceutically acceptable salt thereof and optionally a pharmaceutically acceptable carrier and to a method for the treatment or prevention of a condition or diseaseselected from the group consisting of hypertension, heart failure, such as (acute and chronic) congestive heart failure, left ventricular dysfunction and hypertrophic cardiomyopathy, diabetic cardiac myopathy, supraventricular and ventricular arrhythmias, atrial fibrillation, atrial flutter, detrimental vascular remodeling, myocardial infarction and its sequelae, atherosclerosis, angina (whether unstable or stable), renal insufficiency (diabetic and non-diabetic), heart failure, angina pectoris, diabetes, secondary aldosteronism, primary and secondary pulmonary hypertension, renal failure conditions, such as diabetic nephropathy, glomerulonephritis, scleroderma, glomerular sclerosis, proteinuria of primary renal disease, and also renal vascular hypertension, diabetic retinopathy, the management of other vascular disorders, such as migraine, peripheral vascular disease, Raynaud's disease, luminal hyperplasia, cognitive dysfunction, such as Alzheimer's, glaucoma and stroke, comprising administering a therapeutically effective amount of the pharmaceutical composition to a mammal in need thereof. Excerpt(s): The renin angiotensin system is a complex hormonal system comprised of a large molecular weight precursor, angiotensinogen, two processing enzymes, renin and angiotensin converting enzyme (ACE), and the vasoactive mediator angiotensin II (Ang

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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 •

MINIMALLY-INVASIVE DEVICES AND METHODS FOR TREATMENT OF CONGESTIVE HEART FAILURE Inventor(s): Bolduc, Lee R.; (Mountain View, CA), Boyd, Stephen W.; (Redwood City, CA), Donlon, Brian S.; (Los Altos, CA), Gifford, Hanson S. III; (Woodside, CA), Houle, Philip R.; (Palo Alto, CA), Rosenman, Daniel C.; (San Francisco, CA), Stevens, John H.; (Palo Alto, CA) Correspondence: Audley A. Ciamporcero JR.; Johnson & Johnson; One Johnson & Johnson Plaza; New Brunswick; NJ; 08933-7003; US Patent Application Number: 20030102000 Date filed: March 24, 2000 Abstract: A method of treatment of congestive heart failure comprises the steps of introducing an aortic occlusion catheter through a patient's peripheral artery, the aortic occlusion catheter having an occluding member movable from a collapsed position to an expanded position; positioning the occluding member in the patient's ascending aorta; moving the occluding member from the collapsed shape to the expanded shape after the positioning step; introducing cardioplegic fluid into the patient's coronary blood vessels to arrest the patient's heart; maintaining circulation of oxygenated blood through the patient's arterial system; and reshaping an outer wall of the patient's heart while the heart is arrested so as to reduce the transverse dimension of the left ventricle. The ascending aorta may be occluded and cardioplegic fluid delivered by means of an occlusion balloon attached to the distal end of an elongated catheter positioned

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transluminally in the aorta from a femoral, subclavian, or other appropriate peripheral artery. Excerpt(s): This application is a Continuation of co-pending U.S. patent application Ser. No. 08/685,262, filed Jul. 23, 1996, which is a Continuation-In-Part of application Ser. No. 08/485,600, filed Jun. 7, 1995, which is a Continuation-In-Part of application Ser. No. 08/281,962, filed Jul. 28, 1994, which is a Continuation-In-Part of application Ser. No. 08/163,241, filed Dec. 6, 1993, now U.S. Pat. No. 5,571,2215, which is a Continuation-InPart of application Ser. No. 08/023,778, filed Feb. 22, 1993, now issued as U.S. Pat. No. 5,452,733, the complete disclosures of which are hereby incorporated herein by reference for all purposes. In congestive heart failure or CHF, the heart has become so enlarged as a result of viral infection, myocardial infarction or other disease that it is unable to pump at a sufficient rate to maintain adequate circulation of blood throughout the body. As a result, blood backs up into the lungs, causing shortness of breath and other symptoms, and, if left untreated, the disease can lead to death. For some patients, the CHF may be treated effectively with medication. However, in many cases, the disease progresses to a point at which the patient requires a heart transplant. Unfortunately, due to a donor shortage, of the 40,000 patients who may require a transplant each year, only 2500 actually get one, with up to 15-20% of patients dying while on the waiting list for a donor heart. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Muscle cells and their use in cardiac repair Inventor(s): Dinsmore, Jonathan; (Brookline, MA), Edge, Albert; (Cambridge, MA) Correspondence: Monica R. Gerber, M.D., PH.D.; Choate, Hall & Stewart; Exchange Place; 53 State Street; Boston; MA; 02109; US Patent Application Number: 20030113301 Date filed: March 21, 2002 Abstract: Muscle cells and methods for using the muscle cells are provided. In one embodiment, the invention provides transplantable skeletal muscle cell compositions and their methods of use. In one embodiment, the muscle cells can be transplanted into patients having disorders characterized by insufficient cardiac function, e.g., congestive heart failure, in a subject by administering the skeletal myoblasts to the subject. The muscle cells can be autologous, allogeneic, or xenogeneic to the recipient. Excerpt(s): This application claims priority to U.S. Provisional Application No. 60/145,849, filed on Jul. 23, 1999, and to U.S. National application Ser. No. 09/624,885, filed on Jul. 24, 2000, both of which are incorporated herein in their entirety. Heart disease is the predominant cause of disability and death in all industrialized nations. Cardiac disease can lead to decreased quality of life and long term hospitalization. In addition, in the United States, it accounts for about 335 deaths per 100,000 individuals (approximately 40% of the total mortality) overshadowing cancer, which follows with 183 deaths per 100,000 individuals. Four categories of heart disease account for about 8590% of all cardiac-related deaths. These categories are: ischemic heart disease, hypertensive heart disease and pulmonary hypertensive heart disease, valvular disease, and congenital heart disease. Ischemic heart disease, in its various forms, accounts for about 60-75% of all deaths caused by heart disease. In addition, the incidence of heart failure is increasing in the United States. One of the factors that renders ischemic heart disease so devastating is the inability of the cardiac muscle cells to divide and

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repopulate areas of ischemic heart damage. As a result, cardiac cell loss as a result of injury or disease is irreversible. Human to human heart transplants have become the most effective form of therapy for severe heart damage. Many transplant centers now have one-year survival rates exceeding 80-90% and five-year survival rates above 70% after cardiac transplantation. Heart transplantation, however, is severely limited by the scarcity of suitable donor organs. In addition to the difficulty in obtaining donor organs, the expense of heart transplantation prohibits its widespread application. Another unsolved problem is graft rejection. Foreign hearts are poorly tolerated by the recipient and are rapidly destroyed by the immune system in the absence of immunosuppressive drugs. While immunosuppressive drugs may be used to prevent rejection, they also block desirable immune responses such as those against bacterial and viral infections, thereby placing the recipient at risk of infection. Infections, hypertension, and renal dysfunction caused by cyclosporin, rapidly progressive coronary atherosclerosis, and immunosuppressant-related cancers have been major complications however. 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 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

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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 •

Polypeptide sequences of human EDG-1c Inventor(s): Bergsma, Derk J.; (Berwyn, PA), Chambers, Jonathan K.; (Cambridge, GB), Chan, Winnie; (West Chester, PA), Jensen, Pamela Joy; (Wayne, PA), Johnson, Randall K.; (Ardmore, PA), Khandoudi, Nassirah; (Saint Gregoire, FR), Livi, George P.; (Havertown, PA), Robert, Phillipe; (Saint Gregoire, FR), Stadel, Jeffrey M.; (Wayne, PA), Wilson, Shelagh; (Hertford, GB) Correspondence: Glaxosmithkline; Corporate Intellectual Property - Uw2220; P.O. Box 1539; King OF Prussia; PA; 19406-0939; US Patent Application Number: 20030082743 Date filed: January 12, 2001 Abstract: Human EDG-1c polypeptidees and polynucleotides and methods for producing such polypeptides by recombinant techniques are disclosed. Human EDG-1c is identified as a selective receptor for sphingosine-1-phosphate ("S-1-P") and for dihydro S-1-P. Also disclosed are methods for discovering agonists and antagonists of the interaction between S-1-P and di-hydro S-1-P and their cellular receptor, human EDG1c, which may have utility in the treatment of several human diseases and disorders, including, but not limited to the treatment of infections such as bacterial, fungal, protozoan and viral infections, particularly infections such as bacterial, fungal, protozoan and viral infections, particularly infections caused by HIV-1 or HIV-2; pain; cancers; diabetes, obesity; anorexia; bulimia; asthma; Parkinson's disease; acute heart failure; hypotension; hypertension; urinary retention; osteoporosis; angina pectoris; myocardial infarction; stroke; congestive heart failure; left ventricular hypertrophy; arrythmias; restenosis after coronary artery angioplasty; vascular sclerosis; deleterious fibrosis; atherosclerosis; inflammation; angiogenesis; wound healing; ulcers; asthma; allergies; benign prostatic hypertrophy; migraine; vomiting; psychotic and neurological disorders, including anxiety, schizophrenia, manic depression, depression, delirium, dementia, and severe mental retardation; degenerative diseases, such as neurodegenerative diseases and ischemic stroke; and dyskinesias, such as Huntington's disease or Gilles dela Tourett's syndrome. Excerpt(s): This application claims benefit to the earlier provisional U.S. application Ser. Nos. 60/077,369, filed on Mar. 9, 1998, and 60/087,102, filed on May 28, 1998, the contents of which are incorporated herein by reference in their entirety. This invention relates to newly identified polypeptides and polynucleotides 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 the G-protein coupled receptors, hereinafter referred to as human EDG-1c receptor. This invention also relates to methods for discovering agonists and antagonists of the interaction between sphingosine 1-phosphate (hereinafter referred to as "S-1-P") and dihydro sphingosine 1-phosphate (also known as sphingoanine 1-phosphate and

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hereinafter referred to as "di-hydro S-1-P") and their cellular receptor, human EDG-1c receptor. The invention also relates to the use of human EDG-1c polynucleotides and polypeptides in therapy and in identifying compounds which may be agonists, antagonists and/or inhibitors which are potentially useful in therapy, and to production of such polypeptides and polynucleotides. The drug discovery process is currently undergoing a fundamental revolution as it embraces `functional genomics`, that is, high throughput genome- or gene-based biology. This approach is rapidly superseding earlier approaches based on `positional cloning`. A phenotype, that is a biological function or genetic disease, would be identified and this would then be tracked back to the responsible gene, based on its genetic map position. 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 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

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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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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 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

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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 •

Temperature monitoring of congestive heart failure patients as an indicator of worsening condition Inventor(s): Casscells, Samuel Ward III; (Houston, TX), Payvar, Saeed; (Houston, TX) Correspondence: Tim L. Burgess, P.C.; 402 Oak Lane; Houston; TX; 77024; US Patent Application Number: 20030092975 Date filed: September 19, 2002 Abstract: Indication of worsening health condition in patients with congestive heart failure using the analysis of the speed and pattern of temperature change in a way that is individualized toward patient's health condition. Excerpt(s): This application is a continuation-in-part of U.S. patent application Ser. No. 09/519,122, filed Mar. 6, 2000, which claims priority to U.S. provisional patent application No. 60/123,342, filed Mar. 8, 1999. The present invention generally relates to apparatus and methods for continuous monitoring of health condition in patients with congestive heart failure. Congestive heart failure ("CHF") is a chronic inability of the heart to maintain an adequate output of blood from one or both ventricles of the heart to meet the metabolic demands of the tissues. With a markedly weakened left ventricle or right ventricle or both, the volume of blood presented to the heart is in excess of the heart's capacity to move it along. Consequently, fluid builds up behind the heart. With a weakened left ventricle or right ventricle or both, there is a shift of large volumes of blood from the systemic circulation into the pulmonary (lung) circulation. If the inability to move the volume of blood forward is due to a left heart problem without the right side failing as well, blood continues to be pumped into the lungs by the normal right heart, while it is not pumped adequately out of the lungs by the left heart. As the volume of blood in the lungs increases, the pulmonary vessels enlarge, pulmonary venous congestion develops, and, once the pulmonary capillary pressure rises above a critical point, fluid begins to filter out of the capillaries into the interstitial spaces and alveoli (air sacs in the lungs where exchange of oxygen and carbon dioxide occurs), resulting in pulmonary edema. Subsequently this can lead to pleural effusion (effusion is the escape of fluid into a part) and abdominal effusion. If the abnormality lies in the right heart or the pulmonary arteries, limiting the ability to move blood forward, then congestion occurs behind the right heart (causing pleural effusion and/or build up of fluid in the abdomen).

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Therapeutic uses of milk mineral fortified food products Inventor(s): Bastian, Eric Douglas; (Twin Falls, ID), Ward, Loren Spencer; (Twin Falls, ID) Correspondence: Banner & Witcoff; 1001 G Street N W; Suite 1100; Washington; DC; 20001; US Patent Application Number: 20030118662 Date filed: December 5, 2001 Abstract: Food products fortified with a therapeutically effective amount of milk mineral are administered for the treatment of high blood pressure, stroke, obesity, kidney stones, colon cancer, breast cancer, head and neck tumors, premenstrual syndrome, postpartum depression, hypertensive disorders of pregnancy, Type-2 diabetes, depression, asthma, inflammatory bowel disease, attention deficit disorder, migraine headaches, kidney disease, hypercholesterolaemia, congestive heart failure, or immune deficiency. Excerpt(s): The present invention is directed to milk mineral fortified food products and, more particularly to the treatment of high blood pressure, stroke, obesity, and various other disorders by administering food products fortified with a therapeutically effective amount of milk mineral. The natural milk minerals, especially calcium, magnesium, phosphorus, potassium and zinc, are of great importance in nutrition. Their importance is widely recognized for proper teeth and bone formation, as well as for skeletal structure development. During the period of late teenage to young adulthood, however, significant reductions in dietary calcium intake often occur. This is particularly true of the female population, where reduced dietary calcium intake usually occurs much earlier in life compared to their male counterparts. It has been observed that females are especially susceptible to a prolonged calcium deficit over their life span. This calcium deficit is believed to contribute to the greater incidence of osteoporosis in postmenopausal women. Calcium supplements and calcium-fortified foods containing calcium in such forms as calcium carbonate, calcium lactate, calcium citrate, calcium chloride, and calcium hydroxide have been proposed. These forms of calcium, however, can yield undesirable flavors and/or can strip desirable aroma and flavor compounds from food products. More significantly, these types of supplements deliver only calcium (no other minerals) and lack the balanced and pure form of the milk minerals (including calcium, phosphorus, potassium, magnesium, and zinc) present in milk and dairy products. As a result, these forms of calcium are less easily absorbed by the body and are inferior to milk and dairy products from a nutritional standpoint. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Treatments for a patient with congestive heart failure Inventor(s): Lattouf, Omar M.; (Atlanta, GA) Correspondence: Coudert Brothers Llp; 3rd Floor; 600 Beach Street; San Francisco; CA; 94109-1312; US Patent Application Number: 20030120264 Date filed: December 6, 2002

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Abstract: The invention is directed to two minimally invasive therapeutic procedures, particularly for patients with congestive heart failure, and devices and systems for such procedures. One procedure involves providing a valved passageway through the patient's left ventricular wall at the apex of the patient's heart and advancing instruments through the valved passageway to connect the valve leaflets of the patient's heart valve, e.g. the mitral valve, in a "Bow-Tie" configuration to prevent or minimize regurgitation through the valve. The second procedure involves advancing a pacing lead and a pacing lead implanting device through a trocar in the patient's chest and implanting the pacing lead on an exposed epicardial region of the patient's heart wall. The pacing lead has a penetrating electrode which is secured within the heart wall. One or both procedures may be performed on a patient with CHF.Improved devices for these procedures include a minimally invasive grasping device having an inner lumen for advancing connecting members and other instruments through the device to the distal end thereof. Other improved devices include a pacing lead implant instrument which is releasably secured by its distal end to the exposed heart wall to facilitate penetration of the pacing lead electrode into the heart wall. Other improved instruments include a leaflet connector with an artificial cordae tendenae strand secured to an end of the leaflet connector. Excerpt(s): This application is a continuation-in-part of application Ser. No. 10/295,390, filed on Nov. 15, 2002 which is related to and claims the priority of Provisional Application No. 60/340,062, filed Dec. 8, 2001, Provisional Application Serial No. 60/365,918, filed Mar. 20, 2002, and Provisional Application Serial No. 60/369,988, filed Apr. 4, 2002. The entire contents of these applications are incorporated herein by reference. This invention is directed to therapeutic procedures for a patient's heart and to instruments and systems for such procedures. The invention is particularly suitable for treating a patient suffering from the symptoms of congestive heart failure (CHF), and particularly to those CHF patients exhibiting mitral valve regurgitation (MVR) and/or those exhibiting intraventricular conduction delay with resulting disturbance of the synchronous right and/or left ventricular contractility. There are over five million patients in the United States suffering from CHF and there are more than seven hundred thousand new cases of CHF each year. For many of these patients medical therapy is not very successful. Recent trials have shown that a significant number of CHF patient's benefit from percutaneous ventricular pacing where pacing leads are introduced percutaneously and advanced within the patient's vasculature until the leads are disposed within the patient's coronary sinus. However, ventricular pacing has not been found successful for a significant number of CHF patients for a variety of reasons. For example, in a number of procedures the coronary sinus cannot be cannulate due to dilated cardiomyopathy (the deformity of the heart which accompanies CHF) and, even if the coronary sinus is cannulated, the pacing leads can become displaced rendering them ineffective. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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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

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Use of propargyl glycine amino propargyl diol compounds for treatment of congestive heart failure Inventor(s): Hanson, Gunnar J.; (Skokie, IL), John, Baran S.; (Winnetka, IL) Correspondence: Pharmacia Corporation; Corporate Patent Department; 800 North Lindbergh - 04e; ST. Louis; MO; 63167; US Patent Application Number: 20030135066 Date filed: November 28, 2001 Abstract: Compounds characterized generally as propargyl glycine amino propargyl diol derivatives are useful as renin inhibitors for the treatment of hypertension. Compounds of particular interest are those of Formula I 1wherein A is selected from CO and SO.sub.2 wherein X is selected from oxygen atom and methylene; wherein each of R.sub.1 and R.sub.9 is a group independently selected from hydrido, methyl, ethyl, npropyl, isopropyl, benzyl, b, b, b-trifluoroethyl, t-butyloxycarbonyl and methoxymethylcarbonyl, and wherein the nitrogen atom to which R.sub.1 and R.sub.9 are attached may be combined with oxygen to form an N-oxide; wherein R.sub.2 is selected from hydrido, methyl, ethyl and isopropyl; wherein R.sub.3 is selected from benzyl, cyclohexylmethyl, phenethyl, imidazolemethyl, pyridylmethyl and 2pyridylethyl; wherein each of R.sub.5 and R.sub.8 is independently propargyl or a propargyl-containing moiety; wherein R.sub.7 is cyclohexylmethyl; wherein each of R.sub.4 and R.sub.6 is independently selected from hydrido and methyl; wherein each of R.sub.11 and R.sub.12 is independently selected from hydrido, alkyl and phenyl; wherein m is zero; and wherein n is a number selected from zero through three; or a pharmaceutically-acceptable salt thereof.

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Excerpt(s): This application is a continuation-in-part of U.S. application Ser. No. 07/784,272 filed Oct. 29, 1991. Renin-inhibiting compounds are known for control of hypertension. Of particular interest herein are compounds useful as renin inhibiting agents. Renin is a proteolytic enzyme produced and secreted into the bloodstream by the juxtaglomerular cells of the kidney. In the bloodstream, renin cleaves a peptide bond in the serum protein angiotensinogen to produce a decapeptide known as angiotensin I. A second enzyme known as angiotensin converting enzyme, cleaves angiotensin I to produce the octapeptide known as angiotensin II. Angiotensin II is a potent pressor agent responsible for vasoconstriction and elevation of cardiovascular pressure. Attempts have been made to control hypertension by blocking the action of renin or by blocking the formation of angiotensin II in the body with inhibitors of angiotensin I converting enzyme. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Use of somatostatin receptor agonists in the treatment of human disorders of sleep hypoxia and oxygen deprivation Inventor(s): Young, Charles W.; (New York, NY) Correspondence: Frommer Lawrence & Haug; 745 Fifth Avenue- 10th FL.; New York; NY; 10151; US Patent Application Number: 20030083241 Date filed: October 25, 2002 Abstract: The invention relates to a method of treating diverse human disorders that may arise, in part, out of sleep hypoxia and oxygen deprivation occurring in the context of sleep apnea/hypopnea disturbances. The disorders that may be treated by the invention comprise gastroesophageal reflux disease (GERD), asthma-associated gastroesophageal reflux (GER), GER-associated asthma, asthma, cardiomyopathy, cardioarrhythmia, congestive heart failure, sudden infant death syndrome, and diverse neurologic conditions. The mode of treatment uses somatostatin receptor ligands (SstRLs), particularly somatostatin-receptor agonists. The invention concerns the method of treatment utilizing, and compositions comprising SstRLs and somatostatin receptor agonists, including agonists of the somatostatin receptor types 2 and 5, particularly, the type 2A receptor (SsR-2A), including octreotide and lanreotide. Excerpt(s): The invention relates to a method of using somatostatin receptor agonists to treat diverse human disorders of sleep hypoxia and oxygen deprivation, including but not limited to: 1) gastroesophageal reflux disease (GERD), asthma-associated gastroesophageal reflux (GER), GER-associated asthma, and asthma; 2) obstructive sleep apnea (OSA), and OSA-associated conditions, including GER, asthma, cardiomyopathy, cardioarrhythmia, congestive heart failure, median nerve compression neuropathy (carpal tunnel syndrome) and cognitive impairment; as well as sleep apnea-associated sudden infant death syndrome (SIDS), 3) central sleep apnea (CSA), as well as CSAassociated conditions, including GER, cardiomyopathy, cardioarrhythmia, congestive heart failure, and cognitive impairment; 4) mixed pattern sleep apneas, including but not limited to post-vascular occlusion sleep apnea, dementia-associated sleep apnea, amyotrophic lateral sclerosis-associated sleep apnea, myasthenia gravis-associated sleep apnea, and alcoholism-related sleep apnea; 5) excess calpain-activation disorders in tissues where the injured cell population expresses somatostatin receptors; including, but not limited to the central nervous system, peripheral nerves, heart, liver, kidney, and gastrointestinal tract. Various documents are cited in this text. Citations in the text can

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be by way of a citation to a document in the reference list, e.g., by way of an author(s) and document year, whereby full citation in the text is to a document that may or may not also be listed in the reference list. There is no admission that any of the various documents cited in this text are prior art as to the present invention. Any document having as an author or inventor person or persons named as an inventor herein is a document that is not by another as to the inventor of entity herein. All documents cited in this text ("herein cited documents") and all documents cited or referenced in herein cited documents are hereby incorporated herein by reference. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

Keeping Current In order to stay informed about patents and patent applications dealing with congestive 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 “congestive heart failure” (or synonyms) into the “Term 1” box. After clicking on the search button, scroll down to see the various patents which have been granted to date on congestive heart failure. You can also use this procedure to view pending patent applications concerning congestive 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 CONGESTIVE HEART FAILURE Overview This chapter provides bibliographic book references relating to congestive heart failure. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on congestive 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 “congestive 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 congestive 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

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up to date reference work describing the dental management of patients with selected 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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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

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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. •

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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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) 4321380; 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

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specific dental management. Two appendices cover infection control and the therapeutic management of common oral lesions. A detailed subject index concludes the text. •

Primer on Kidney Diseases. 2nd ed Source: San Diego, CA: Academic Press. 1998. 542 p. 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.

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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

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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 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. •

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.

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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 “congestive heart failure” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “congestive heart failure” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “congestive heart failure” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •

Adherence with Medication in Congestive Heart Failure (Round Table Series (RTS)) by C. George (Editor); ISBN: 1853153060; http://www.amazon.com/exec/obidos/ASIN/1853153060/icongroupinterna

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Basic Mechanism of Congestive Heart Failure by Alice Tripp; ISBN: 0070652236; http://www.amazon.com/exec/obidos/ASIN/0070652236/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 Cardiac Failure: Pathophysiology and Treatment (Fundamental and Clinical Cardiology, Vol 14) by David B. Barnett, et al; ISBN: 0824788214; http://www.amazon.com/exec/obidos/ASIN/0824788214/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 by Charles Kaye Friedberg; ISBN: 0808906704; http://www.amazon.com/exec/obidos/ASIN/0808906704/icongroupinterna

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Congestive Heart Failure by Cydney R. Michaelson (Editor); ISBN: 0801634431; http://www.amazon.com/exec/obidos/ASIN/0801634431/icongroupinterna

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Congestive heart failure by Albert N. Brest; ISBN: 0846301563; http://www.amazon.com/exec/obidos/ASIN/0846301563/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 Clinical Issues (American Heart Association Monograph Series) by Gemma T. Kennedy, Michael H. Crawford (Editor); ISBN:

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0879935863; http://www.amazon.com/exec/obidos/ASIN/0879935863/icongroupinterna •

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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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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Drug treatment of congestive heart failure : proceedings of a symposium; ISBN: 0895743027; http://www.amazon.com/exec/obidos/ASIN/0895743027/icongroupinterna

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Ibopamine in the Management of Congestive Heart Failure by J.P. Bounhoure (Editor), P. Magrassi (Editor); ISBN: 3805553099; http://www.amazon.com/exec/obidos/ASIN/3805553099/icongroupinterna

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Living Well With Congestive Heart Failure: A Self-Management Program; ISBN: 1560664800; http://www.amazon.com/exec/obidos/ASIN/1560664800/icongroupinterna

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Milrinone : investigation of new inotropic therapy for congestive heart failure; ISBN: 0890043361; http://www.amazon.com/exec/obidos/ASIN/0890043361/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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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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Oxidative Stress and Cardiac Failure by Marrick L. Kukin (Editor), Valentin Fuster (Editor) (2003); ISBN: 0879937092; http://www.amazon.com/exec/obidos/ASIN/0879937092/icongroupinterna

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Prazosin : pharmacology, hypertension, and congestive heart failure; ISBN: 0808913700; http://www.amazon.com/exec/obidos/ASIN/0808913700/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

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Cardiology, Berlin, September 1994 (Cardiology) by Peter A. Van Zwieten (Editor) (1997); ISBN: 3805565208; http://www.amazon.com/exec/obidos/ASIN/3805565208/icongroupinterna •

Success With Heart Failure: Help and Hope for Those with Congestive Heart Failure by Marc A. Silver, Marc Silver; ISBN: 0738206008; http://www.amazon.com/exec/obidos/ASIN/0738206008/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 (Contemporary Cardiology Ser) by James C. Fang (Editor), Gregory S. Couper (Editor) (2003); ISBN: 1588290344; http://www.amazon.com/exec/obidos/ASIN/1588290344/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, Michael B. Fowler (2001); ISBN: 0312252528; http://www.amazon.com/exec/obidos/ASIN/0312252528/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

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 “congestive 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:11 •

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]

11

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.

Books

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•

Congestive heart failure. Author: Benack, Raymond Thomas,; Year: 2003; Springfield, Ill., Thomas [c1966]

•

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]

•

Congestive heart failure; etiology, prevention, management. Author: United States. Public Health Service. Division of Chronic Diseases.; Year: 1965; Washington,

•

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

•

Starling's law of the heart; its significance in chronic congestive heart failure. Author: Loe, Ping-kian.; Year: 2002; Djakarta, Keng Po, 1961

•

Symposium on congestive heart failure. Author: Blumgart, Herrman Ludwig,; Year: 1965; New York, American

•

The management of congestive heart failure Author: Gazes, Peter C.,; Year: 1966; Chicago: Year Book Medical Publishers, 1980

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

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. 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

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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 CONGESTIVE HEART FAILURE Overview In this chapter, we show you how to keep current on multimedia sources of information on congestive 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 congestive heart failure is the Combined Health Information Database. You will need to limit your search to “Videorecording” and “congestive 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 “congestive heart failure” (or synonyms) into the “For these words:” box. The following is a typical result when searching for video recordings on congestive heart failure: •

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

218 Congestive Heart Failure

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 Congestive 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 congestive 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 congestive 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]

•

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

•

Congestive heart failure [slide] Source: Committee on Medical Education of the American Heart Association; Year: 1974; Format: Slide; [New York: The Assn., 1974]

•

Congestive heart failure [slide] Source: Miles Pharmaceuticals; [developed and produced by Gardiner-Caldwell SynerMed]; Year: 1985; Format: Slide; [S.l.]: GardinerCaldwell SynerMed, c1985

•

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]

•

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

•

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

•

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

•

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

•

Congestive heart failure and cardiac impedance [slide] Source: Michael Ritota; Year: 1979; Format: Slide; Newark, N. J.: M.E.D.S. Corp., c1979

•

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

•

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

•

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

•

High-output cardiac failure [videorecording] Source: presented by the Department of Medicine, Emory University, School of Medicine; Year: 1985; Format: Videorecording; Atlanta, Ga.: The University, 1985

•

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

•

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

•

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 CONGESTIVE HEART FAILURE Overview In this chapter, we suggest a number of news sources and present various periodicals that cover congestive heart failure.

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

Gene mutation linked with congestive heart failure Source: Reuters Medical News Date: February 27, 2003

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•

Mitoxantrone associated with congestive heart failure in MS patients Source: Reuters Medical News Date: September 23, 2002

•

Blood test helps catch congestive heart failure Source: Reuters Health eLine Date: July 17, 2002 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 “congestive 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 “congestive heart failure” (or synonyms). If you know the name of a company that is relevant to congestive 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 “congestive heart failure” (or synonyms).

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 “congestive 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 congestive 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.

•

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

224 Congestive Heart Failure

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.

Academic Periodicals covering Congestive Heart Failure Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to congestive heart failure. In addition to these sources, you can search for articles covering congestive 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.” 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 congestive 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 non-profit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at http://www.usp.org/. The USP currently provides standards for over 3,700 medications. The resulting USP DI Advice for the Patient can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database, located at http://www.fda.gov/cder/da/da.htm. While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopeia (USP). Below, we have compiled a list of medications associated with congestive 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,

226 Congestive Heart Failure

etc.). The following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to congestive heart failure: Amiodarone •

Systemic - U.S. Brands: Cordarone http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202029.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

Anticoagulants •

Systemic - U.S. Brands: Coumadin; Miradon http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202050.html

Carvedilol •

Systemic - U.S. Brands: Coreg http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203636.html

Cyclosporine •

Systemic - U.S. Brands: Neoral; Sandimmune; SangCya http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202176.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

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Heparin •

Systemic - U.S. Brands: Calciparine; Liquaemin http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202280.html

Hydralazine •

Systemic - U.S. Brands: http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202280.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

Torsemide •

Systemic - U.S. Brands: Demadex http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202740.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/.

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PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html. Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee. If you have any questions about a medical treatment, the FDA may have an office near you. Look for their number in the blue pages of the phone book. You can also contact the FDA through its toll-free number, 1-888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.

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APPENDICES

231

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 Institute12: •

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/

12

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

232 Congestive Heart Failure

•

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.13 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:14 •

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

13

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). 14 See http://www.nlm.nih.gov/databases/databases.html.

234 Congestive Heart Failure

•

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 Gateway15 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.16 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “congestive 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 56909 590 935 126 97 58657

HSTAT17 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.18 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.19 Simply search by “congestive heart failure” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

15

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

16

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). 17 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 18 19

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 Biologists20 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.21 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.22 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/.

20 Adapted 21

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. 22 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 congestive 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 congestive 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 congestive 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 “congestive heart failure”:

238 Congestive Heart Failure

•

Guides on congestive heart failure Congestive Heart Failure

•

Other guides Arrhythmia http://www.nlm.nih.gov/medlineplus/arrhythmia.html Congenital Heart Disease http://www.nlm.nih.gov/medlineplus/congenitalheartdisease.html Heart Attack http://www.nlm.nih.gov/medlineplus/heartattack.html Heart Diseases http://www.nlm.nih.gov/medlineplus/heartdiseases.html Heart Failure http://www.nlm.nih.gov/medlineplus/heartfailure.html Pacemakers and Implantable Defibrillators http://www.nlm.nih.gov/medlineplus/pacemakersandimplantabledefibrillators.ht l Sepsis http://www.nlm.nih.gov/medlineplus/sepsis.html Streptococcal Infections http://www.nlm.nih.gov/medlineplus/streptococcalinfections.html

Within the health topic page dedicated to congestive 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.ama-assn.org/public/journals/patient/archive/pat0206.htm Learning about Heart Failure Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=337

•

Diagnosis/Symptoms Blood Tests: Seeking Clues about Your Heartâ€™s 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

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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 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

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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 •

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

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Heart Failure Care Inconsistent Source: 11/09/2003, American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=3016913 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 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

242 Congestive Heart Failure

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 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 congestive 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: •

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 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

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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. •

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 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

244 Congestive Heart Failure

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 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).

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 “congestive heart failure” (or synonyms). The following was recently posted: •

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=congestive+AND+heart+AND+failure

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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 congestive 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

•

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

•

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

•

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

•

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

•

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

•

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

Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to congestive heart failure. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with congestive 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 congestive 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

246 Congestive Heart Failure

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 “congestive 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 “congestive 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 “congestive 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 “congestive heart failure” (or a synonym) into the search box, and click “Submit Query.”

247

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.23

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

23

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

248 Congestive Heart Failure

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)24: •

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

•

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

•

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

•

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

•

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

•

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

•

California: Gateway Health Library (Sutter Gould Medical Foundation)

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

24

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

Finding Medical Libraries

249

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

250 Congestive Heart Failure

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

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/

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

252 Congestive Heart Failure

•

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

•

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

•

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

•

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

253

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

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

•

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

•

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

•

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

•

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

•

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

•

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

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

Basic Guidelines for Congestive Heart Failure Bacterial endocarditis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000681.htm Cardiomyopathy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001105.htm Chf Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000158.htm Copd Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000091.htm Ihss Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000192.htm

254 Congestive Heart Failure

•

Signs & Symptoms for Congestive Heart Failure Anasarca Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003103.htm Anxiety Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003211.htm Apnea Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003069.htm Bloating Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003123.htm Cough Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003072.htm Cyanosis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003215.htm Difficulty breathing Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003075.htm Dyspnea Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003075.htm Edema Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003103.htm Fatigue Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003088.htm Hepatomegaly Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003275.htm Hypotension Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003083.htm Lethargy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003088.htm Nocturia Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003141.htm Orthopnea Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003076.htm Paroxysmal nocturnal dyspnea Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003076.htm Peripheral edema Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003104.htm

Online Glossaries 255

Rales Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003323.htm Tachypnea Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003071.htm Weakness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003174.htm •

Diagnostics and Tests for Congestive Heart Failure BUN Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003474.htm Cardiac catheterization Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003419.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 Echocardiography Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003869.htm ENG Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003448.htm Erythrocyte sedimentation rate Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003638.htm Sedimentation rate Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003638.htm TSH Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003684.htm X-ray Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003337.htm

•

Surgery and Procedures for Congestive Heart Failure Cardiac transplant Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003003.htm Valve repair Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002954.htm Valve replacement Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002954.htm

256 Congestive Heart Failure

•

Background Topics for Congestive Heart Failure Cardiovascular Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002310.htm Systemic Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002294.htm

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

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

•

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

257

CONGESTIVE HEART FAILURE DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 1-phosphate: A drug that halts cell suicide in human white blood cells. [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] Abscess: Accumulation of purulent material in tissues, organs, or circumscribed spaces, usually associated with signs of infection. [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] Accommodation: Adjustment, especially that of the eye for various distances. [EU] Acetohexamide: A sulfonylurea hypoglycemic agent that is metabolized in the liver to 1hydrohexamide. [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] Actin: Essential component of the cell skeleton. [NIH] Activities of Daily Living: The performance of the basic activities of self care, such as dressing, ambulation, eating, etc., in rehabilitation. [NIH] Acute renal: A condition in which the kidneys suddenly stop working. In most cases, kidneys can recover from almost complete loss of function. [NIH] 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] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine

258 Congestive Heart Failure

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] Adipose Tissue: Connective tissue composed of fat cells lodged in the meshes of areolar tissue. [NIH] Adjunctive Therapy: Another treatment used together with the primary treatment. Its purpose is to assist the primary treatment. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] 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] 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] Aerobic Exercise: A type of physical activity that includes walking, jogging, running, and dancing. Aerobic training improves the efficiency of the aerobic energy-producing systems that can improve cardiorespiratory endurance. [NIH] Aetiology: Study of the causes of disease. [EU] Afferent: Concerned with the transmission of neural impulse toward the central part of the nervous system. [NIH] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, 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

Dictionary 259

complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Afterload: The tension produced by the heart muscle after contraction. [EU] Agar: A complex sulfated polymer of galactose units, extracted from Gelidium cartilagineum, Gracilaria confervoides, and related red algae. It is used as a gel in the preparation of solid culture media for microorganisms, as a bulk laxative, in making emulsions, and as a supporting medium for immunodiffusion and immunoelectrophoresis. [NIH]

Age of Onset: The age or period of life at which a disease or the initial symptoms or manifestations of a disease appear in an individual. [NIH] Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Air Sacs: Thin-walled sacs or spaces which function as a part of the respiratory system in birds, fishes, insects, and mammals. [NIH] Airway: A device for securing unobstructed passage of air into and out of the lungs during general anesthesia. [NIH] Akinesia: 1. Absence or poverty of movements. 2. The temporary paralysis of a muscle by the injection of procaine. [EU] Albumin: 1. Any protein that is soluble in water and moderately concentrated salt solutions and is coagulable by heat. 2. Serum albumin; the major plasma protein (approximately 60 per cent of the total), which is responsible for much of the plasma colloidal osmotic pressure and serves as a transport protein carrying large organic anions, such as fatty acids, bilirubin, and many drugs, and also carrying certain hormones, such as cortisol and thyroxine, when their specific binding globulins are saturated. Albumin is synthesized in the liver. Low serum levels occur in protein malnutrition, active inflammation and serious hepatic and renal disease. [EU] Aldehydes: Organic compounds containing a carbonyl group in the form -CHO. [NIH] 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] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alkaline: Having the reactions of an alkali. [EU] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Alkalosis: A pathological condition that removes acid or adds base to the body fluids. [NIH]

260 Congestive Heart Failure

Allantois: An embryonic diverticulum of the hindgut of reptiles, birds, and mammals; in man its blood vessels give rise to those of the umbilical cord. [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] Allergic Rhinitis: Inflammation of the nasal mucous membrane associated with hay fever; fits may be provoked by substances in the working environment. [NIH] Allogeneic: Taken from different individuals of the same species. [NIH] Allopurinol: A xanthine oxidase inhibitor that decreases uric acid production. [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] Alveoli: Tiny air sacs at the end of the bronchioles in the lungs. [NIH] 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] Amino-terminal: The end of a protein or polypeptide chain that contains a free amino group (-NH2). [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] Amnion: The extraembryonic membrane which contains the embryo and amniotic fluid. [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

Dictionary 261

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] Anabolic: Relating to, characterized by, or promoting anabolism. [EU] Anabolic Steroids: Chemical derivatives of testosterone that are used for anabolic promotion of growth and repair of body tissues and the development of male sexual characteristics. [NIH] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] 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] Angiocardiography: Radiography of the heart and great vessels after injection of a contrast medium. [NIH] Angiogenesis: Blood vessel formation. Tumor angiogenesis is the growth of blood vessels

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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. 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] 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]

Anterior Cerebral Artery: Artery formed by the bifurcation of the internal carotid artery. Branches of the anterior cerebral artery supply the caudate nucleus, internal capsule, putamen, septal nuclei, gyrus cinguli, and surfaces of the frontal lobe and parietal lobe. [NIH] Anthracycline: A member of a family of anticancer drugs that are also antibiotics. [NIH] Antianginal: Counteracting angina or anginal conditions. [EU] Antiarrhythmic: An agent that prevents or alleviates cardiac arrhythmia. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]

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

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thinner. [NIH] Antidiabetic: An agent that prevents or alleviates diabetes. [EU] Antidiuretic: Suppressing the rate of urine formation. [EU] Antidote: A remedy for counteracting a poison. [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 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] 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] Antiviral: Destroying viruses or suppressing their replication. [EU] Antrectomy: An operation to remove the upper portion of the stomach, called the antrum. This operation helps reduce the amount of stomach acid. It is used when a person has complications from ulcers. [NIH] Anuria: Inability to form or excrete urine. [NIH] Anus: The opening of the rectum to the outside of the body. [NIH] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] 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] 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] 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]

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Aromatic: Having a spicy odour. [EU] 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] Articular: Of or pertaining to a joint. [EU] 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] Aspartic: The naturally occurring substance is L-aspartic acid. One of the acidic-amino-acids is obtained by the hydrolysis of proteins. [NIH] Aspartic Endopeptidases: A sub-subclass of endopeptidases that depend on an aspartic acid residue for their activity. EC 3.4.23. [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] Atherogenic: Causing the formation of plaque in the lining of the arteries. [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]

Atrial Natriuretic Factor: A potent natriuretic and vasodilatory peptide or mixture of different-sized low molecular weight peptides derived from a common precursor and secreted by the heart atria. All these peptides share a sequence of about 20 amino acids. [NIH] Atrioventricular: Pertaining to an atrium of the heart and to a ventricle. [EU]

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Atrioventricular Node: A small nodular mass of specialized muscle fibers located in the interatrial septum near the opening of the coronary sinus. It gives rise to the atrioventricular bundle of the conduction system of the heart. [NIH] Atrium: A chamber; used in anatomical nomenclature to designate a chamber affording entrance to another structure or organ. Usually used alone to designate an atrium of the heart. [EU] Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] Auditory: Pertaining to the sense of hearing. [EU] Autoantibodies: Antibodies that react with self-antigens (autoantigens) of the organism that produced them. [NIH] Autoantigens: Endogenous tissue constituents that have the ability to interact with autoantibodies and cause an immune response. [NIH] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] 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] Axillary: Pertaining to the armpit area, including the lymph nodes that are located there. [NIH]

Axillary Vein: The venous trunk of the upper limb; a continuation of the basilar and brachial veins running from the lower border of the teres major muscle to the outer border of the first rib where it becomes the subclavian vein. [NIH] Axons: Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body. [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

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the urine. [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] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [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] 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 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] Biliopancreatic Diversion: A surgical procedure which diverts pancreatobiliary secretions via the duodenum and the jejunum into the colon, the remaining small intestine being anastomosed to the stomach after antrectomy. The procedure produces less diarrhea than does jejunoileal bypass. [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] Biological Markers: Measurable and quantifiable biological parameters (e.g., specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution

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in a population, presence of biological substances) which serve as indices for health- and physiology-related assessments, such as disease risk, psychiatric disorders, environmental exposure and its effects, disease diagnosis, metabolic processes, substance abuse, pregnancy, cell line development, epidemiologic studies, etc. [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] Biomechanics: The study of the application of mechanical laws and the action of forces to living structures. [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] Bisoprolol: A cardioselective beta-1-adrenergic blocker. It is effective in the management of hypertension and angina pectoris. [NIH] Bladder: The organ that stores urine. [NIH] Bloating: Fullness or swelling in the abdomen that often occurs after meals. [NIH] Blood Cell Count: A count of the number of leukocytes and erythrocytes per unit volume in a sample of venous blood. A complete blood count (CBC) also includes measurement of the hemoglobin, hematocrit, and erythrocyte indices. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Glucose: Glucose in blood. [NIH] Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blot: To transfer DNA, RNA, or proteins to an immobilizing matrix such as nitrocellulose. [NIH]

Body Fluids: Liquid components of living organisms. [NIH]

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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] 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] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] Brachial: All the nerves from the arm are ripped from the spinal cord. [NIH] Brachial Plexus: The large network of nerve fibers which distributes the innervation of the upper extremity. The brachial plexus extends from the neck into the axilla. In humans, the nerves of the plexus usually originate from the lower cervical and the first thoracic spinal cord segments (C5-C8 and T1), but variations are not uncommon. [NIH] Bradycardia: Excessive slowness in the action of the heart, usually with a heart rate below 60 beats per minute. [NIH] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Brain Hypoxia: Lack of oxygen leading to unconsciousness. [NIH] Brain Infarction: The formation of an area of necrosis in the brain, including the cerebral hemispheres (cerebral infarction), thalami, basal ganglia, brain stem (brain stem infarctions), or cerebellum secondary to an insufficiency of arterial or venous blood flow. [NIH] Brain Ischemia: Localized reduction of blood flow to brain tissue due to arterial obtruction or systemic hypoperfusion. This frequently occurs in conjuction with brain hypoxia. Prolonged ischemia is associated with brain infarction. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]

Breakdown: A physical, metal, or nervous collapse. [NIH] Bromine: A halogen with the atomic symbol Br, atomic number 36, and atomic weight 79.904. It is a volatile reddish-brown liquid that gives off suffocating vapors, is corrosive to the skin, and may cause severe gastroenteritis if ingested. [NIH] Bronchi: The larger air passages of the lungs arising from the terminal bifurcation of the trachea. [NIH] Bronchioles: The tiny branches of air tubes in the lungs. [NIH] Bronchitis: Inflammation (swelling and reddening) of the bronchi. [NIH]

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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] Bundle-Branch Block: A form of heart block in which one ventricle is excited before the other because of absence of conduction in one of the branches of the bundle of His. [NIH] 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] Calcineurin: A calcium- and calmodulin-binding protein present in highest concentrations in the central nervous system. Calcineurin is composed of two subunits. A catalytic subunit, calcineurin A, and a regulatory subunit, calcineurin B, with molecular weights of about 60 kD and 19 kD, respectively. Calcineurin has been shown to dephosphorylate a number of phosphoproteins including histones, myosin light chain, and the regulatory subunit of cAMP-dependent protein kinase. It is involved in the regulation of signal transduction and is the target of an important class of immunophilin-immunosuppressive drug complexes in T-lymphocytes that act by inhibiting T-cell activation. EC 3.1.3.-. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Calcium Carbonate: Carbonic acid calcium salt (CaCO3). An odorless, tasteless powder or crystal that occurs in nature. It is used therapeutically as a phosphate buffer in hemodialysis patients and as a calcium supplement. [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 Chloride: A salt used to replenish calcium levels, as an acid-producing diuretic, and as an antidote for magnesium poisoning. [NIH] Calcium Hydroxide: Ca(OH)2. A white powder that has many therapeutic uses. Because of its ability to stimulate mineralization, it is found in many dental formulations. [NIH] Calmodulin: A heat-stable, low-molecular-weight activator protein found mainly in the brain and heart. The binding of calcium ions to this protein allows this protein to bind to cyclic nucleotide phosphodiesterases and to adenyl cyclase with subsequent activation. Thereby this protein modulates cyclic AMP and cyclic GMP levels. [NIH] Calpain: Cysteine proteinase found in many tissues. Hydrolyzes a variety of endogenous proteins including neuropeptides, cytoskeletal proteins, proteins from smooth muscle, cardiac muscle, liver, platelets and erythrocytes. Two subclasses having high and low calcium sensitivity are known. Removes Z-discs and M-lines from myofibrils. Activates phosphorylase kinase and cyclic nucleotide-independent protein kinase. [NIH] Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU] 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

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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] 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] Carboxylic Acids: Organic compounds containing the carboxy group (-COOH). This group of compounds includes amino acids and fatty acids. Carboxylic acids can be saturated, unsaturated, or aromatic. [NIH] Carcinogenic: Producing carcinoma. [EU] Cardenolides: C(23)-steroids with methyl groups at C-10 and C-13 and a five-membered lactone at C-17. They are aglycone constituents of cardiac glycosides and must have at least one double bond in the molecule. the class includes cardadienolides and cardatrienolides. Members include digitoxin and digoxin and their derivatives and the strophanthins. [NIH] Cardiac: Having to do with the heart. [NIH] Cardiac arrest: A sudden stop of heart function. [NIH] 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] Cardiomyopathy: A general diagnostic term designating primary myocardial disease, often of obscure or unknown etiology. [EU] 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] Cardiorespiratory: Relating to the heart and lungs and their function. [EU] Cardioselective: Having greater activity on heart tissue than on other tissue. [EU]

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Cardiotonic: 1. Having a tonic effect on the heart. 2. An agent that has a tonic effect on the heart. [EU] Cardiotoxic: Having a poisonous or deleterious effect upon the heart. [EU] Cardiotoxicity: Toxicity that affects the heart. [NIH] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular 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] 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] Carpal Tunnel Syndrome: A median nerve injury inside the carpal tunnel that results in symptoms of pain, numbness, tingling, clumsiness, and a lack of sweating, which can be caused by work with certain hand and wrist postures. [NIH] Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Case series: A group or series of case reports involving patients who were given similar treatment. Reports of case series usually contain detailed information about the individual patients. This includes demographic information (for example, age, gender, ethnic origin) and information on diagnosis, treatment, response to treatment, and follow-up after treatment. [NIH] 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] Cause of Death: Factors which produce cessation of all vital bodily functions. They can be analyzed from an epidemiologic viewpoint. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing

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specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Respiration: The metabolic process of all living cells (animal and plant) in which oxygen is used to provide a source of energy for the cell. [NIH] Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Centrifugation: A method of separating organelles or large molecules that relies upon differential sedimentation through a preformed density gradient under the influence of a gravitational field generated in a centrifuge. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral Infarction: The formation of an area of necrosis in the cerebrum caused by an insufficiency of arterial or venous blood flow. Infarcts of the cerebrum are generally classified by hemisphere (i.e., left vs. right), lobe (e.g., frontal lobe infarction), arterial distribution (e.g., infarction, anterior cerebral artery), and etiology (e.g., embolic infarction). [NIH]

Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Cervical: Relating to the neck, or to the neck of any organ or structure. Cervical lymph nodes are located in the neck; cervical cancer refers to cancer of the uterine cervix, which is the lower, narrow end (the "neck") of the uterus. [NIH] Character: In current usage, approximately equivalent to personality. The sum of the relatively fixed personality traits and habitual modes of response of an individual. [NIH] Chemoreceptors: Cells specialized to detect chemical substances and relay that information 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] Chemotaxis: The movement of cells or organisms toward or away from a substance in response to its concentration gradient. [NIH] Chest Pain: Pressure, burning, or numbness in the chest. [NIH] Chlorine: A greenish-yellow, diatomic gas that is a member of the halogen family of

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elements. It has the atomic symbol Cl, atomic number 17, and atomic weight 70.906. It is a powerful irritant that can cause fatal pulmonary edema. Chlorine is used in manufacturing, as a reagent in synthetic chemistry, for water purification, and in the production of chlorinated lime, which is used in fabric bleaching. [NIH] Cholecystectomy: Surgical removal 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] 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] Chorion: The outermost extraembryonic membrane. [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] 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] 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] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]

Clinical study: A research study in which patients receive treatment in a clinic or other medical facility. Reports of clinical studies can contain results for single patients (case reports) or many patients (case series or clinical trials). [NIH]

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Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Clitoral: Pertaining to the clitoris. [EU] Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Coenzyme: An organic nonprotein molecule, frequently a phosphorylated derivative of a water-soluble vitamin, that binds with the protein molecule (apoenzyme) to form the active enzyme (holoenzyme). [EU] 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] Colitis: Inflammation of the colon. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Collagenases: Enzymes that catalyze the degradation of collagen by acting on the peptide bonds. EC 3.4.24.-. [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] 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

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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] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Concomitant: Accompanying; accessory; joined with another. [EU] Conduction: The transfer of sound waves, heat, nervous impulses, or electricity. [EU] Cone: One of the special retinal receptor elements which are presumed to be primarily concerned with perception of light and color stimuli when the eye is adapted to light. [NIH] Confusion: A mental state characterized by bewilderment, emotional disturbance, lack of clear thinking, and perceptual disorientation. [NIH] Congestion: Excessive or abnormal accumulation of blood in a part. [EU] Congestive heart failure: Weakness of the heart muscle that leads to a buildup of fluid in body tissues. [NIH] Conjugated: Acting or operating as if joined; simultaneous. [EU] Conjunctiva: The mucous membrane that lines the inner surface of the eyelids and the anterior part of the sclera. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue Cells: A group of cells that includes fibroblasts, cartilage cells, adipocytes, smooth muscle cells, and bone cells. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH] Constipation: Infrequent or difficult evacuation of feces. [NIH] Constitutional: 1. Affecting the whole constitution of the body; not local. 2. Pertaining to the constitution. [EU] Constriction: The act of constricting. [NIH] Constriction, Pathologic: The condition of an anatomical structure's being constricted beyond normal dimensions. [NIH]

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Consultation: A deliberation between two or more physicians concerning the diagnosis and the proper method of treatment in a case. [NIH] Consumption: Pulmonary tuberculosis. [NIH] Contractile Proteins: Proteins which participate in contractile processes. They include muscle proteins as well as those found in other cells and tissues. In the latter, these proteins participate in localized contractile events in the cytoplasm, in motile activity, and in cell aggregation phenomena. [NIH] Contractility: Capacity for becoming short in response to a suitable stimulus. [EU] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] 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] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [NIH] Corneal Ulcer: Loss of epithelial tissue from the surface of the cornea due to progressive erosion and necrosis of the tissue; usually caused by bacterial, fungal, or viral infection. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary Angiography: Radiography of the vascular system of the heart muscle after injection of a contrast medium. [NIH] Coronary Arteriosclerosis: Thickening and loss of elasticity of the coronary arteries. [NIH] Coronary Artery Bypass: Surgical therapy of ischemic coronary artery disease achieved by grafting a section of saphenous vein, internal mammary artery, or other substitute between the aorta and the obstructed coronary artery distal to the obstructive lesion. [NIH] Coronary Circulation: The circulation of blood through the coronary vessels of the heart. [NIH]

Coronary heart disease: A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Corpus: The body of the uterus. [NIH] Corpus Luteum: The yellow glandular mass formed in the ovary by an ovarian follicle that has ruptured and discharged its ovum. [NIH]

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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] Critical Care: Health care provided to a critically ill patient during a medical emergency or crisis. [NIH] 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] Cysteine Endopeptidases: Endopeptidases which have a cysteine involved in the catalytic process. This group of enzymes is inactivated by sulfhydryl reagents. EC 3.4.22. [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, including T and B cells. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a

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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] De novo: In cancer, the first occurrence of cancer in the body. [NIH] Decompensation: Failure of compensation; cardiac decompensation is marked by dyspnea, venous engorgement, and edema. [EU] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] 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 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] Delivery of Health Care: The concept concerned with all aspects of providing and distributing health services to a patient population. [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] Demyelinating Diseases: Diseases characterized by loss or dysfunction of myelin in the central or peripheral nervous system. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive

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stimuli from other neurons. [NIH] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Dental Caries: Localized destruction of the tooth surface initiated by decalcification of the enamel followed by enzymatic lysis of organic structures and leading to cavity formation. If left unchecked, the cavity may penetrate the enamel and dentin and reach the pulp. The three most prominent theories used to explain the etiology of the disase are that acids produced by bacteria lead to decalcification; that micro-organisms destroy the enamel protein; or that keratolytic micro-organisms produce chelates that lead to decalcification. [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] Deprivation: Loss or absence of parts, organs, powers, or things that are needed. [EU] Desensitization: The prevention or reduction of immediate hypersensitivity reactions by administration of graded doses of allergen; called also hyposensitization and immunotherapy. [EU] Desmin: An intermediate filament protein found predominantly in smooth, skeletal, and cardiac muscle cells. Localized at the Z line. MW 50,000 to 55,000 is species dependent. [NIH] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] 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 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]

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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 procedure: A method used to identify a disease. [NIH] Dialyzer: A part of the hemodialysis machine. (See hemodialysis under dialysis.) The dialyzer has two sections separated by a membrane. One section holds dialysate. The other holds the patient's blood. [NIH] Diaphragm: The musculofibrous partition that separates the thoracic cavity from the abdominal cavity. Contraction of the diaphragm increases the volume of the thoracic cavity aiding inspiration. [NIH] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Diastole: Period of relaxation of the heart, especially the ventricles. [NIH] Diastolic: Of or pertaining to the diastole. [EU] Diastolic blood pressure: The minimum pressure that remains within the artery when the heart is at rest. [NIH] Diastolic pressure: The lowest pressure to which blood pressure falls between contractions of the ventricles. [NIH] 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] 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] Dilator: A device used to stretch or enlarge an opening. [NIH] Diltiazem: A benzothiazepine derivative with vasodilating action due to its antagonism of the actions of the calcium ion in membrane functions. It is also teratogenic. [NIH] Dimerization: The process by which two molecules of the same chemical composition form a condensation product or polymer. [NIH]

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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] Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [EU] Disorientation: The loss of proper bearings, or a state of mental confusion as to time, place, or identity. [EU] Disposition: A tendency either physical or mental toward certain diseases. [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 consciousness and, thus separated, function as a unitary whole. [EU] Dissociative Disorders: Sudden temporary alterations in the normally integrative functions of consciousness. [NIH] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Diuresis: Increased excretion of urine. [EU] Diuretic: A drug that increases the production of urine. [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] 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] 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 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]

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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] 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]

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] Dysmenorrhoea: Painful menstruation. [EU] Dysphoric: A feeling of unpleasantness and discomfort. [NIH] Dyspnea: Difficult or labored breathing. [NIH] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] Echocardiography: Ultrasonic recording of the size, motion, and composition of the heart and surrounding tissues. The standard approach is transthoracic. [NIH] 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] Effusion: The escape of fluid into a part or tissue, as an exudation or a transudation. [EU] Ejection fraction: A measure of ventricular contractility, equal to normally 65 8 per cent; lower values indicate ventricular dysfunction. [EU] Elasticity: Resistance and recovery from distortion of shape. [NIH] Elastin: The protein that gives flexibility to tissues. [NIH] 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] 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

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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] 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] Emergency Medicine: A branch of medicine concerned with an individual's resuscitation, transportation and care from the point of injury or beginning of illness through the hospital or other emergency treatment facility. [NIH] Emergency Treatment: First aid or other immediate intervention for accidents or medical conditions requiring immediate care and treatment before definitive medical and surgical management can be procured. [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] Enalapril: An angiotensin-converting enzyme inhibitor that is used to treat hypertension. [NIH]

Endarterectomy: Surgical excision, performed under general anesthesia, of the atheromatous tunica intima of an artery. When reconstruction of an artery is performed as an endovascular procedure through a catheter, it is called atherectomy. [NIH] 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] Endometrium: The layer of tissue that lines the uterus. [NIH] Endopeptidases: A subclass of peptide hydrolases. They are classified primarily by their catalytic mechanism. Specificity is used only for identification of individual enzymes. They comprise the serine endopeptidases, EC 3.4.21; cysteine endopeptidases, EC 3.4.22; aspartic endopeptidases, EC 3.4.23, metalloendopeptidases, EC 3.4.24; and a group of enzymes yet to be assigned to any of the above sub-classes, EC 3.4.99. EC 3.4.-. [NIH]

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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] 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] 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] 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] 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] Epidemiologic Studies: Studies designed to examine associations, commonly, hypothesized causal relations. They are usually concerned with identifying or measuring the effects of risk factors or exposures. The common types of analytic study are case-control studies, cohort studies, and cross-sectional studies. [NIH] 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

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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] Epitopes: Sites on an antigen that interact with specific antibodies. [NIH] Erectile: The inability to get or maintain an erection for satisfactory sexual intercourse. Also called impotence. [NIH] Erection: The condition of being made rigid and elevated; as erectile tissue when filled with blood. [EU] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Escalation: Progressive use of more harmful drugs. [NIH] Esophageal: Having to do with the esophagus, the muscular tube through which food passes from the throat to the stomach. [NIH] Esophagitis: Inflammation, acute or chronic, of the esophagus caused by bacteria, chemicals, or trauma. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]

Estrogen: One of the two female sex hormones. [NIH] Ethanol: A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Euthanasia: The act or practice of putting to death people or animals suffering from incurable conditions or diseases. [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,

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salves, etc. [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] 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] Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extracellular Matrix Proteins: Macromolecular organic compounds that contain carbon, hydrogen, oxygen, nitrogen, and usually, sulfur. These macromolecules (proteins) form an intricate meshwork in which cells are embedded to construct tissues. Variations in the relative types of macromolecules and their organization determine the type of extracellular matrix, each adapted to the functional requirements of the tissue. The two main classes of macromolecules that form the extracellular matrix are: glycosaminoglycans, usually linked 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] 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]

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Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]

Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH] Femoral: Pertaining to the femur, or to the thigh. [EU] 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] Fetal Membranes: Thin layers of tissue which surround the embryo or fetus and provide for its nutrition, respiration, excretion and protection; they are the yolk sac, allantois, amnion, and chorion. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibrillation: A small, local, involuntary contraction of muscle, invisible under the skin, resulting from spontaneous activation of single muscle cells or muscle fibres. [EU] Fibrin: A protein derived from fibrinogen in the presence of thrombin, which forms part of the blood clot. [NIH] 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] 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] Fluid Therapy: Therapy whose basic objective is to restore the volume and composition of the body fluids to normal with respect to water-electrolyte balance. Fluids may be administered intravenously, orally, by intermittent gavage, or by hypodermoclysis. [NIH] Fluorine: A nonmetallic, diatomic gas that is a trace element and member of the halogen family. It is used in dentistry as flouride to prevent dental caries. [NIH] Foam Cells: Lipid-laden macrophages originating from monocytes or from smooth muscle cells. [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] Fold: A plication or doubling of various parts of the body. [NIH] Foot Ulcer: Lesion on the surface of the skin of the foot, usually accompanied by inflammation. The lesion may become infected or necrotic and is frequently associated with diabetes or leprosy. [NIH] 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

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pancreatic islets against damage by cytokines and prevents myocardial and pulmonary perfusion injuries. [NIH] Friction: Surface resistance to the relative motion of one body against the rubbing, sliding, rolling, or flowing of another with which it is in contact. [NIH] Frontal Lobe: The anterior part of the cerebral hemisphere. [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] 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] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [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]

Gastroenteritis: An acute inflammation of the lining of the stomach and intestines, characterized by anorexia, nausea, diarrhoea, abdominal pain, and weakness, which has various causes, including food poisoning due to infection with such organisms as Escherichia coli, Staphylococcus aureus, and Salmonella species; consumption of irritating food or drink; or psychological factors such as anger, stress, and fear. Called also enterogastritis. [EU] Gastroesophageal Reflux: Reflux of gastric juice and/or duodenal contents (bile acids, pancreatic juice) into the distal esophagus, commonly due to incompetence of the lower esophageal sphincter. Gastric regurgitation is an extension of this process with entry of fluid into the pharynx or mouth. [NIH] Gastroesophageal Reflux Disease: Flow of the stomach's contents back up into the esophagus. Happens when the muscle between the esophagus and the stomach (the lower esophageal sphincter) is weak or relaxes when it shouldn't. May cause esophagitis. Also called esophageal reflux or reflux esophagitis. [NIH] Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gelatin: A product formed from skin, white connective tissue, or bone collagen. It is used as a protein food adjuvant, plasma substitute, hemostatic, suspending agent in pharmaceutical

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preparations, and in the manufacturing of capsules and suppositories. [NIH] Gelatinases: A class of enzymes that catalyzes the degradation of gelatin by acting on the peptide bonds. EC 3.4.24.-. [NIH] 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] Generator: Any system incorporating a fixed parent radionuclide from which is produced a daughter radionuclide which is to be removed by elution or by any other method and used in a radiopharmaceutical. [NIH] Genetic 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 Engineering: Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc. [NIH] Genetic Markers: A phenotypically recognizable genetic trait which can be used to identify a genetic locus, a linkage group, or a recombination event. [NIH] 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] Genomics: The systematic study of the complete DNA sequences (genome) of organisms. [NIH]

Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Geriatric: Pertaining to the treatment of the aged. [EU] Ginseng: An araliaceous genus of plants that contains a number of pharmacologically active agents used as stimulants, sedatives, and tonics, especially in traditional medicine. [NIH] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Gliclazide: An oral sulfonylurea hypoglycemic agent which stimulates insulin secretion. [NIH]

Glipizide: An oral hypoglycemic agent which is rapidly absorbed and completely metabolized. [NIH] Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus. [EU]

Glomerular Filtration Rate: The volume of water filtered out of plasma through glomerular capillary walls into Bowman's capsules per unit of time. It is considered to be equivalent to inulin clearance. [NIH]

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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] 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] 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] Glutamate: Excitatory neurotransmitter of the brain. [NIH] Glyburide: An antidiabetic sulfonylurea derivative with actions similar to those of chlorpropamide. [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] Goats: Any of numerous agile, hollow-horned ruminants of the genus Capra, closely related to the sheep. [NIH] Gonadal: Pertaining to a gonad. [EU] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] 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

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replace diseased or injured tissue removed from another part of the body. [NIH] Graft Rejection: An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient. [NIH] Grafting: The operation of transfer of tissue from one site to another. [NIH] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] 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] Guanylate Cyclase: An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2. [NIH] Hair 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] Haplotypes: The genetic constitution of individuals with respect to one member of a pair of allelic genes, or sets of genes that are closely linked and tend to be inherited together such as those of the major histocompatibility complex. [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 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 attack: A seizure of weak or abnormal functioning of the heart. [NIH]

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Heart Catheterization: Procedure which includes placement of catheter, recording of intracardiac and intravascular pressure, obtaining blood samples for chemical analysis, and cardiac output measurement, etc. Specific angiographic injection techniques are also involved. [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Heart Transplantation: The transference of a heart from one human or animal to another. [NIH]

Heart Valves: Flaps of tissue that prevent regurgitation of blood from the ventricles to the atria or from the pulmonary arteries or aorta to the ventricles. [NIH] Heartbeat: One complete contraction of the heart. [NIH] Hematocrit: Measurement of the volume of packed red cells in a blood specimen by centrifugation. The procedure is performed using a tube with graduated markings or with automated blood cell counters. It is used as an indicator of erythrocyte status in disease. For example, anemia shows a low hematocrit, polycythemia, high values. [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] 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

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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] 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]

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 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] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] 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] Host: Any animal that receives a transplanted graft. [NIH] Humoral: Of, relating to, proceeding from, or involving a bodily humour - now often used of endocrine factors as opposed to neural or somatic. [EU] Humour: 1. A normal functioning fluid or semifluid of the body (as the blood, lymph or bile) especially of vertebrates. 2. A secretion that is itself an excitant of activity (as certain hormones). [EU] Hybridomas: Cells artificially created by fusion of activated lymphocytes with neoplastic cells. The resulting hybrid cells are cloned and produce pure or "monoclonal" antibodies or T-cell products, identical to those produced by the immunologically competent parent, and continually grow and divide as the neoplastic parent. [NIH] Hydrocephalus: Excessive accumulation of cerebrospinal fluid within the cranium which

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may be associated with dilation of cerebral ventricles, intracranial hypertension; headache; lethargy; urinary incontinence; and ataxia (and in infants macrocephaly). This condition may be caused by obstruction of cerebrospinal fluid pathways due to neurologic abnormalities, intracranial hemorrhages; central nervous system infections; brain neoplasms; craniocerebral trauma; and other conditions. Impaired resorption of cerebrospinal fluid from the arachnoid villi results in a communicating form of hydrocephalus. Hydrocephalus ex-vacuo refers to ventricular dilation that occurs as a result of brain substance loss from cerebral infarction and other conditions. [NIH] 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] Hydroxamic Acids: A class of weak acids with the general formula R-conhoh. [NIH] Hydroxylysine: A hydroxylated derivative of the amino acid lysine that is present in certain collagens. [NIH] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hypercapnia: A clinical manifestation of abnormal increase in the amount of carbon dioxide in arterial blood. [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, Pulmonary: Increased pressure within the pulmonary circulation, usually secondary to cardiac or pulmonary disease. [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]

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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] Hypocapnia: Clinical manifestation consisting of a deficiency of carbon dioxide in arterial blood. [NIH] 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, 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] Hypothyroidism: Deficiency of thyroid activity. In adults, it is most common in women and is characterized by decrease in basal metabolic rate, tiredness and lethargy, sensitivity to cold, and menstrual disturbances. If untreated, it progresses to full-blown myxoedema. In infants, severe hypothyroidism leads to cretinism. In juveniles, the manifestations are intermediate, with less severe mental and developmental retardation and only mild symptoms of the adult form. When due to pituitary deficiency of thyrotropin secretion it is called secondary hypothyroidism. [EU] 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] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]

Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunity: Nonsusceptibility to the invasive or pathogenic microorganisms or to the toxic effect of antigenic substances. [NIH]

effects

of

foreign

Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer

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factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunofluorescence: A technique for identifying molecules present on the surfaces of cells or in tissues using a highly fluorescent substance coupled to a specific antibody. [NIH] Immunogenic: Producing immunity; evoking an immune response. [EU] Immunoglobulin: A protein that acts as an antibody. [NIH] 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] Immunosuppressant: An agent capable of suppressing immune responses. [EU] 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 vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH] Incompetence: Physical or mental inadequacy or insufficiency. [EU] Incontinence: Inability to control the flow of urine from the bladder (urinary incontinence) or the escape of stool from the rectum (fecal incontinence). [NIH] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the

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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] Inflammatory bowel disease: A general term that refers to the inflammation of the colon and rectum. Inflammatory bowel disease includes ulcerative colitis and Crohn's disease. [NIH]

Influenza: An acute viral infection involving the respiratory tract. It is marked by inflammation of the nasal mucosa, the pharynx, and conjunctiva, and by headache and severe, often generalized, myalgia. [NIH] Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called 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] Inlay: In dentistry, a filling first made to correspond with the form of a dental cavity and then cemented into the cavity. [NIH] Innervation: 1. The distribution or supply of nerves to a part. 2. The supply of nervous energy or of nerve stimulus sent to a part. [EU] 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] 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] Insomnia: Difficulty in going to sleep or getting enough sleep. [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] Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune,

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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] Intercostal: Situated between the ribs. [EU] 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-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] Interleukin-6: Factor that stimulates the growth and differentiation of human B-cells and is also a growth factor for hybridomas and plasmacytomas. It is produced by many different cells including T-cells, monocytes, and fibroblasts. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] 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] Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] 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] Inulin: A starch found in the tubers and roots of many plants. Since it is hydrolyzable to fructose, it is classified as a fructosan. It has been used in physiologic investigation for determination of the rate of glomerular function. [NIH] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]

Invertebrates: Animals that have no spinal column. [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] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Irritable Bowel Syndrome: A disorder that comes and goes. Nerves that control the muscles in the GI tract are too active. The GI tract becomes sensitive to food, stool, gas, and stress. Causes abdominal pain, bloating, and constipation or diarrhea. Also called spastic colon or mucous colitis. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Ischemic stroke: A condition in which the blood supply to part of the brain is cut off. Also called "plug-type" strokes. Blocked arteries starve areas of the brain controlling sight, speech, sensation, and movement so that these functions are partially or completely lost. Ischemic stroke is the most common type of stroke, accounting for 80 percent of all strokes. Most ischemic strokes are caused by a blood clot called a thrombus, which blocks blood flow in the arteries feeding the brain, usually the carotid artery in the neck, the major vessel bringing blood to the brain. When it becomes blocked, the risk of stroke is very high. [NIH] Isoenzyme: Different forms of an enzyme, usually occurring in different tissues. The isoenzymes of a particular enzyme catalyze the same reaction but they differ in some of their properties. [NIH] 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] Isosorbide: 1,4:3,6-Dianhydro D-glucitol. Chemically inert osmotic diuretic used mainly to treat hydrocephalus; also used in glaucoma. [NIH] Jejunoileal Bypass: A surgical procedure consisting of the anastomosis of the proximal part of the jejunum to the distal portion of the ileum, so as to bypass the nutrient-absorptive segment of the small intestine, to treat morbid obesity. [NIH] Jejunum: That portion of the small intestine which extends from the duodenum to the ileum; called also intestinum jejunum. [EU] 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] Keratoconus: A disorder characterized by an irregular corneal surface (cone-shaped) resulting in blurred and distorted images. [NIH] Ketone Bodies: Chemicals that the body makes when there is not enough insulin in the

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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 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] Kinetic: Pertaining to or producing motion. [EU] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Laminin: Large, noncollagenous glycoprotein with antigenic properties. It is localized in the basement membrane lamina lucida and functions to bind epithelial cells to the basement membrane. Evidence suggests that the protein plays a role in tumor invasion. [NIH] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] 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] Laxative: An agent that acts to promote evacuation of the bowel; a cathartic or purgative. [EU]

Left ventricular assist device: A mechanical device used to increase the heart's pumping ability. [NIH] Length of Stay: The period of confinement of a patient to a hospital or other health facility. [NIH]

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Leprosy: A chronic granulomatous infection caused by Mycobacterium leprae. The granulomatous lesions are manifested in the skin, the mucous membranes, and the peripheral nerves. Two polar or principal types are lepromatous and tuberculoid. [NIH] Leptin: A 16-kD peptide hormone secreted from white adipocytes and implicated in the regulation of food intake and energy balance. Leptin provides the key afferent signal from fat cells in the feedback system that controls body fat stores. [NIH] Lesion: An area of abnormal tissue change. [NIH] Lethal: Deadly, fatal. [EU] Lethargy: Abnormal drowsiness or stupor; a condition of indifference. [EU] Leucocyte: All the white cells of the blood and their precursors (myeloid cell series, lymphoid cell series) but commonly used to indicate granulocytes exclusive of lymphocytes. [NIH]

Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] 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]

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] Ligaments: Shiny, flexible bands of fibrous tissue connecting together articular extremities of bones. They are pliant, tough, and inextensile. [NIH] Ligands: A RNA simulation method developed by the MIT. [NIH] Ligation: Application of a ligature to tie a vessel or strangulate a part. [NIH] Linkage: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] 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] 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]

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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] Lobe: A portion of an organ such as the liver, lung, breast, or brain. [NIH] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Longitudinal study: Also referred to as a "cohort study" or "prospective study"; the analytic method of epidemiologic study in which subsets of a defined population can be identified who are, have been, or in the future may be exposed or not exposed, or exposed in different degrees, to a factor or factors hypothesized to influence the probability of occurrence of a given disease or other outcome. The main feature of this type of study is to observe large numbers of subjects over an extended time, with comparisons of incidence rates in groups that differ in exposure levels. [NIH] 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] Lovastatin: A fungal metabolite isolated from cultures of Aspergillus terreus. The compound is a potent anticholesteremic agent. It inhibits 3-hydroxy-3-methylglutaryl coenzyme A reductase (hydroxymethylglutaryl CoA reductases), which is the rate-limiting enzyme in cholesterol biosynthesis. It also stimulates the production of low-density lipoprotein receptors in the liver. [NIH] Low-density lipoprotein: Lipoprotein that contains most of the cholesterol in the blood. LDL carries cholesterol to the tissues of the body, including the arteries. A high level of LDL increases the risk of heart disease. LDL typically contains 60 to 70 percent of the total serum cholesterol and both are directly correlated with CHD risk. [NIH] Lower Esophageal Sphincter: The muscle between the esophagus and stomach. When a person swallows, this muscle relaxes to let food pass from the esophagus to the stomach. It stays closed at other times to keep stomach contents from flowing back into the esophagus. [NIH]

Lubricants: Oily or slippery substances. [NIH] Lubrication: The application of a substance to diminish friction between two surfaces. It may refer to oils, greases, and similar substances for the lubrication of medical equipment but it can be used for the application of substances to tissue to reduce friction, such as lotions for skin and vaginal lubricants. [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).

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[NIH]

Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] Lymphocyte Count: A count of the number of lymphocytes in the blood. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lysine: An essential amino acid. It is often added to animal feed. [NIH] Lytic: 1. Pertaining to lysis or to a lysin. 2. Producing lysis. [EU] 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] Macula: A stain, spot, or thickening. Often used alone to refer to the macula retinae. [EU] Macula Lutea: An oval area in the retina, 3 to 5 mm in diameter, usually located temporal to the superior pole of the eye and slightly below the level of the optic disk. [NIH] Macular Degeneration: Degenerative changes in the macula lutea of the retina. [NIH] 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] Major Histocompatibility Complex: The genetic region which contains the loci of genes which determine the structure of the serologically defined (SD) and lymphocyte-defined (LD) transplantation antigens, genes which control the structure of the immune responseassociated (Ia) antigens, the immune response (Ir) genes which control the ability of an animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement. [NIH] 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]

Malondialdehyde: The dialdehyde of malonic acid. [NIH] Mammary: Pertaining to the mamma, or breast. [EU] Mania: Excitement of psychotic proportions manifested by mental and physical hyperactivity, disorganization of behaviour, and elevation of mood. [EU] Manic: Affected with mania. [EU] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU]

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Man-made: Ionizing radiation emitted by artificial or concentrated natural, radioactive material or resulting from the operation of high voltage apparatus, such as X-ray apparatus or particle accelerators, of nuclear reactors, or from nuclear explosions. [NIH] 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] Mechanical ventilation: Use of a machine called a ventilator or respirator to improve the exchange of air between the lungs and the atmosphere. [NIH] Mechanoreceptors: Cells specialized to transduce mechanical stimuli and relay that 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] Median Nerve: A major nerve of the upper extremity. In humans, the fibers of the median nerve originate in the lower cervical and upper thoracic spinal cord (usually C6 to T1), travel via the brachial plexus, and supply sensory and motor innervation to parts of the forearm and hand. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] Medical Records: Recording of pertinent information concerning patient's illness or illnesses. [NIH] 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] Melanin: The substance that gives the skin its color. [NIH] Melanocytes: Epidermal dendritic pigment cells which control long-term morphological color changes by alteration in their number or in the amount of pigment they produce and store in the pigment containing organelles called melanosomes. Melanophores are larger cells which do not exist in mammals. [NIH] Melanoma: A form of skin cancer that arises in melanocytes, the cells that produce pigment. Melanoma usually begins in a mole. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning,

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(2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Menopause: Permanent cessation of menstruation. [NIH] 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] Menstruation: The normal physiologic discharge through the vagina of blood and mucosal tissues from the nonpregnant uterus. [NIH] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH] Mental Processes: Conceptual functions or thinking in all its forms. [NIH] Mental Retardation: Refers to sub-average general intellectual functioning which originated during the developmental period and is associated with impairment in adaptive behavior. [NIH]

Mesenchymal: Refers to cells that develop into connective tissue, blood vessels, and lymphatic tissue. [NIH] Metabolic disorder: A condition in which normal metabolic processes are disrupted, usually because of a missing enzyme. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Metabotropic: A glutamate receptor which triggers an increase in production of 2 intracellular messengers: diacylglycerol and inositol 1, 4, 5-triphosphate. [NIH] Metalloendopeptidases: Endopeptidases which use a metal, normally zinc, in the catalytic mechanism. This group of enzymes is inactivated by metal chelators. EC 3.4.24. [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] Metastatic: Having to do with metastasis, which is the spread of cancer from one part of the body to another. [NIH] Metastatic cancer: Cancer that has spread from the place in which it started to other parts of the body. [NIH] Methanol: A colorless, flammable liquid used in the manufacture of formaldehyde and acetic acid, in chemical synthesis, antifreeze, and as a solvent. Ingestion of methanol is toxic and may cause blindness. [NIH] Methionine: A sulfur containing essential amino acid that is important in many body functions. It is a chelating agent for heavy metals. [NIH] Metoprolol: Adrenergic beta-1-blocking agent with no stimulatory action. It is less bound to plasma albumin than alprenolol and may be useful in angina pectoris, hypertension, or cardiac arrhythmias. [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular

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animals, lower algae, lower fungi, bacteria. [NIH] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [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] Microtubules: Slender, cylindrical filaments found in the cytoskeleton of plant and animal cells. They are composed of the protein tubulin. [NIH] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Milrinone: A positive inotropic cardiotonic agent with vasodilator properties. It inhibits cAMP phosphodiesterase activity in myocardium and vascular smooth muscle. Milrinone is a derivative of amrinone and has 20-30 times the ionotropic potency of amrinone. [NIH] Mineralization: The action of mineralizing; the state of being mineralized. [EU] Mitochondria: Parts of a cell where aerobic production (also known as cell respiration) takes place. [NIH] Mitochondrial Swelling: Increase in volume of mitochondria due to an influx of fluid; it occurs in hypotonic solutions due to osmotic pressure and in isotonic solutions as a result of altered permeability of the membranes of respiring mitochondria. [NIH] 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] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH]

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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] Mononuclear: A cell with one nucleus. [NIH] Monophosphate: So called second messenger for neurotransmitters and hormones. [NIH] Mood Disorders: Those disorders that have a disturbance in mood as their predominant feature. [NIH] Motility: The ability to move spontaneously. [EU] 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] Mucus: The viscous secretion of mucous membranes. It contains mucin, white blood cells, water, inorganic salts, and exfoliated cells. [NIH] Multicenter study: A clinical trial that is carried out at more than one medical institution. [NIH]

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] Muscular Dystrophies: A general term for a group of inherited disorders which are

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characterized by progressive degeneration of skeletal muscles. [NIH] Myalgia: Pain in a muscle or muscles. [EU] Myasthenia: Muscular debility; any constitutional anomaly of muscle. [EU] Mydriatic: 1. Dilating the pupil. 2. Any drug that dilates the pupil. [EU] Myelin: The fatty substance that covers and protects nerves. [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 ischemic due to decrease in normal blood supply. The decrease may result from any source including atherosclerotic obstruction, narrowing of the artery, or surgical clamping. Reperfusion can be induced to treat ischemia. Methods include chemical dissolution of an occluding thrombus, administration of vasodilator drugs, angioplasty, catheterization, and artery bypass graft surgery. However, it is thought that reperfusion can itself further damage the ischemic tissue, causing myocardial reperfusion injury. [NIH] Myocardial Reperfusion Injury: Functional, metabolic, or structural changes in ischemic heart muscle thought to result from reperfusion to the ischemic areas. Changes can be fatal to muscle cells and may include edema with explosive cell swelling and disintegration, sarcolemma disruption, fragmentation of mitochondria, contraction band necrosis, enzyme washout, and calcium overload. Other damage may include hemorrhage and ventricular arrhythmias. One possible mechanism of damage is thought to be oxygen free radicals. Treatment currently includes the introduction of scavengers of oxygen free radicals, and injury is thought to be prevented by warm blood cardioplegic infusion prior to reperfusion. [NIH]

Myocarditis: Inflammation of the myocardium; inflammation of the muscular walls of the heart. [EU] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myofibrils: Highly organized bundles of actin, myosin, and other proteins in the cytoplasm of skeletal and cardiac muscle cells that contract by a sliding filament mechanism. [NIH] Myopathy: Any disease of a muscle. [EU] Myopia: That error of refraction in which rays of light entering the eye parallel to the optic axis are brought to a focus in front of the retina, as a result of the eyeball being too long from front to back (axial m.) or of an increased strength in refractive power of the media of the eye (index m.). Called also nearsightedness, because the near point is less distant than it is in emmetropia with an equal amplitude of accommodation. [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

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by a number of physical and chemical aspects, usually resulting in stupor. [NIH] Nasal Mucosa: The mucous membrane lining the nasal cavity. [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] Nearsightedness: The common term for myopia. [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] Nephritis: Inflammation of the kidney; a focal or diffuse proliferative or destructive process which may involve the glomerulus, tubule, or interstitial renal tissue. [EU] 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] Neurodegenerative Diseases: Hereditary and sporadic conditions which are characterized

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by progressive nervous system dysfunction. These disorders are often associated with atrophy of the affected central or peripheral nervous system structures. [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] 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] 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] Nitroglycerin: A highly volatile organic nitrate that acts as a dilator of arterial and venous smooth muscle and is used in the treatment of angina. It provides relief through improvement of the balance between myocardial oxygen supply and demand. Although total coronary blood flow is not increased, there is redistribution of blood flow in the heart when partial occlusion of coronary circulation is effected. [NIH] Nitroprusside: (OC-6-22)-Pentakis(cyano-C)nitrosoferrate(2-). A powerful vasodilator used in emergencies to lower blood pressure or to improve cardiac function. It is also an indicator

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for free sulfhydryl groups in proteins. [NIH] 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 the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclear Proteins: Proteins found in the nucleus of a cell. Do not confuse with nucleoproteins which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus. [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] Nucleoproteins: Proteins conjugated with nucleic acids. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nutritional Support: The administration of nutrients for assimilation and utilization by a patient by means other than normal eating. It does not include fluid therapy which normalizes body fluids to restore water-electrolyte balance. [NIH] Observational study: An epidemiologic study that does not involve any intervention, experimental or otherwise. Such a study may be one in which nature is allowed to take its course, with changes in one characteristic being studied in relation to changes in other characteristics. Analytical epidemiologic methods, such as case-control and cohort study designs, are properly called observational epidemiology because the investigator is observing without intervention other than to record, classify, count, and statistically analyze results. [NIH] Octreotide: A potent, long-acting somatostatin octapeptide analog which has a wide range of physiological actions. It inhibits growth hormone secretion, is effective in the treatment of hormone-secreting tumors from various organs, and has beneficial effects in the management of many pathological states including diabetes mellitus, orthostatic hypertension, hyperinsulinism, hypergastrinemia, and small bowel fistula. [NIH] Ocular: 1. Of, pertaining to, or affecting the eye. 2. Eyepiece. [EU] Office Visits: Visits made by patients to health service providers' offices for diagnosis, treatment, and follow-up. [NIH] Ointments: Semisolid preparations used topically for protective emollient effects or as a vehicle for local administration of medications. Ointment bases are various mixtures of fats, waxes, animal and plant oils and solid and liquid hydrocarbons. [NIH] 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]

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Oliguria: Clinical manifestation of the urinary system consisting of a decrease in the amount of urine secreted. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Ophthalmologic: Pertaining to ophthalmology (= the branch of medicine dealing with the eye). [EU] Opsin: A protein formed, together with retinene, by the chemical breakdown of metarhodopsin. [NIH] Optic Disk: The portion of the optic nerve seen in the fundus with the ophthalmoscope. It is formed by the meeting of all the retinal ganglion cell axons as they enter the optic nerve. [NIH]

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] Orgasm: The crisis of sexual excitement in either humans or animals. [NIH] Orthostatic: Pertaining to or caused by standing erect. [EU] Osmolality: The concentration of osmotically active particles in solution expressed in terms of osmoles of solute per kilogram of solvent. The osmolality is directly proportional to the colligative properties of solutions; osmotic pressure, boiling point elevation, freezing point depression, and vapour pressure lowering. [EU] Osmoles: The standard unit of osmotic pressure. [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] Osteoarthritis: A progressive, degenerative joint disease, the most common form of arthritis, especially in older persons. The disease is thought to result not from the aging process but from biochemical changes and biomechanical stresses affecting articular cartilage. In the foreign literature it is often called osteoarthrosis deformans. [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] 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] Overactive bladder: A condition in which the patient experiences two or all three of the following conditions: [NIH] Overexpress: An excess of a particular protein on the surface of a cell. [NIH] Overweight: An excess of body weight but not necessarily body fat; a body mass index of 25 to 29.9 kg/m2. [NIH] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological

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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] 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] Paclitaxel: Antineoplastic agent isolated from the bark of the Pacific yew tree, Taxus brevifolia. Paclitaxel stabilizes microtubules in their polymerized form and thus mimics the action of the proto-oncogene proteins c-mos. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Pancreatic Juice: The fluid containing digestive enzymes secreted by the pancreas in response to food in the duodenum. [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] Parathyroid: 1. Situated beside the thyroid gland. 2. One of the parathyroid glands. 3. A sterile preparation of the water-soluble principle(s) of the parathyroid glands, ad-ministered parenterally as an antihypocalcaemic, especially in the treatment of acute hypoparathyroidism with tetany. [EU] Parathyroid Glands: Two small paired endocrine glands in the region of the thyroid gland. They secrete parathyroid hormone and are concerned with the metabolism of calcium and phosphorus. [NIH] Parathyroid hormone: A substance made by the parathyroid gland that helps the body store and use calcium. Also called parathormone, parathyrin, or PTH. [NIH] Parietal: 1. Of or pertaining to the walls of a cavity. 2. Pertaining to or located near the parietal bone, as the parietal lobe. [EU] 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]

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Particle Accelerators: Devices which accelerate electrically charged atomic or subatomic particles, such as electrons, protons or ions, to high velocities so they have high kinetic energy. [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 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 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]

Peer Review: An organized procedure carried out by a select committee of professionals in evaluating the performance of other professionals in meeting the standards of their specialty. Review by peers is used by editors in the evaluation of articles and other papers submitted for publication. Peer review is used also in the evaluation of grant applications. It is applied also in evaluating the quality of health care provided to patients. [NIH] Penicillin: An antibiotic drug used to treat infection. [NIH] Penis: The external reproductive organ of males. It is composed of a mass of erectile tissue enclosed in three cylindrical fibrous compartments. Two of the three compartments, the corpus cavernosa, are placed side-by-side along the upper part of the organ. The third compartment below, the corpus spongiosum, houses the urethra. [NIH] Pepsin: An enzyme made in the stomach that breaks down proteins. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Peptide Hydrolases: A subclass of enzymes from the hydrolase class that catalyze the hydrolysis of peptide bonds. Exopeptidases and endopeptidases make up the sub-subclasses for this group. EC 3.4. [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] Pericardial Effusion: Presence of fluid within the pericardium. [NIH] Pericardium: The fibroserous sac surrounding the heart and the roots of the great vessels.

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[NIH]

Periodontal disease: Disease involving the supporting structures of the teeth (as the gums and periodontal membranes). [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 Nerves: The nerves outside of the brain and spinal cord, including the autonomic, cranial, and spinal nerves. Peripheral nerves contain non-neuronal cells and connective tissue as well as axons. The connective tissue layers include, from the outside to the inside, the epineurium, the perineurium, and the endoneurium. [NIH] Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] Peripheral Vascular Disease: Disease in the large blood vessels of the arms, legs, and feet. People who have had diabetes for a long time may get this because major blood vessels in their arms, legs, and feet are blocked and these limbs do not receive enough blood. The signs of PVD are aching pains in the arms, legs, and feet (especially when walking) and foot sores that heal slowly. Although people with diabetes cannot always avoid PVD, doctors say they have a better chance of avoiding it if they take good care of their feet, do not smoke, and keep both their blood pressure and diabetes under good control. [NIH] Peritoneal: Having to do with the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Peritoneal Cavity: The space enclosed by the peritoneum. It is divided into two portions, the greater sac and the lesser sac or omental bursa, which lies behind the stomach. The two sacs are connected by the foramen of Winslow, or epiploic foramen. [NIH] Peritoneal Dialysis: Dialysis fluid being introduced into and removed from the peritoneal cavity as either a continuous or an intermittent procedure. [NIH] Peritoneum: Endothelial lining of the abdominal cavity, the parietal peritoneum covering the inside of the abdominal wall and the visceral peritoneum covering the bowel, the mesentery, and certain of the organs. The portion that covers the bowel becomes the serosal layer of the bowel wall. [NIH] 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] Pheromone: A substance secreted externally by certain animal species, especially insects, to affect the behavior or development of other members of the species. [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] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Phosphorylase: An enzyme of the transferase class that catalyzes the phosphorylysis of a terminal alpha-1,4-glycosidic bond at the non-reducing end of a glycogen molecule, releasing a glucose 1-phosphate residue. Phosphorylase should be qualified by the natural substance acted upon. EC 2.4.1.1. [NIH] 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] 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]

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Pilot study: The initial study examining a new method or treatment. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [NIH] Placenta: A highly vascular fetal organ through which the fetus absorbs oxygen and other nutrients and excretes carbon dioxide and other wastes. It begins to form about the eighth day of gestation when the blastocyst adheres to the decidua. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plaque: A clear zone in a bacterial culture grown on an agar plate caused by localized destruction of bacterial cells by a bacteriophage. The concentration of infective virus in a fluid can be estimated by applying the fluid to a culture and counting the number of. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasma 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] Plasmid: An autonomously replicating, extra-chromosomal DNA molecule found in many bacteria. Plasmids are widely used as carriers of cloned genes. [NIH] Plasmin: A product of the lysis of plasminogen (profibrinolysin) by plasminogen activators. It is composed of two polypeptide chains, light (B) and heavy (A), with a molecular weight of 75,000. It is the major proteolytic enzyme involved in blood clot retraction or the lysis of fibrin and quickly inactivated by antiplasmins. EC 3.4.21.7. [NIH] Plasminogen: Precursor of fibrinolysin (plasmin). It is a single-chain beta-globulin of molecular weight 80-90,000 found mostly in association with fibrinogen in plasma; plasminogen activators change it to fibrinolysin. It is used in wound debriding and has been investigated as a thrombolytic agent. [NIH] Plasticity: In an individual or a population, the capacity for adaptation: a) through gene changes (genetic plasticity) or b) through internal physiological modifications in response to changes of environment (physiological plasticity). [NIH] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Platinum: Platinum. A heavy, soft, whitish metal, resembling tin, atomic number 78, atomic weight 195.09, symbol Pt. (From Dorland, 28th ed) It is used in manufacturing equipment for laboratory and industrial use. It occurs as a black powder (platinum black) and as a

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spongy substance (spongy platinum) and may have been known in Pliny's time as "alutiae". [NIH]

Pleura: The thin serous membrane enveloping the lungs and lining the thoracic cavity. [NIH] Pleural: A circumscribed area of hyaline whorled fibrous tissue which appears on the surface of the parietal pleura, on the fibrous part of the diaphragm or on the pleura in the interlobar fissures. [NIH] Pleural cavity: A space enclosed by the pleura (thin tissue covering the lungs and lining the interior wall of the chest cavity). It is bound by thin membranes. [NIH] Pleural Effusion: Presence of fluid in the pleural cavity resulting from excessive transudation or exudation from the pleural surfaces. It is a sign of disease and not a diagnosis in itself. [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] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postmenopausal: Refers to the time after menopause. Menopause is the time in a woman's life when menstrual periods stop permanently; also called "change of life." [NIH] Postnatal: Occurring after birth, with reference to the newborn. [EU] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Postural: Pertaining to posture or position. [EU] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Potentiate: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] 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

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convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Pravastatin: An antilipemic fungal metabolite isolated from cultures of Nocardia autotrophica. It acts as a competitive inhibitor of HMG CoA reductase (hydroxymethylglutaryl CoA reductases). [NIH] 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] 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] 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] Premenstrual: Occurring before menstruation. [EU] Premenstrual Syndrome: A syndrome occurring most often during the last week of the menstrual cycle and ending soon after the onset of menses. Some of the symptoms are emotional instability, insomnia, headache, nausea, vomiting, abdominal distension, and painful breasts. [NIH] 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 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] Primary Prevention: Prevention of disease or mental disorders in susceptible individuals or populations through promotion of health, including mental health, and specific protection, as in immunization, as distinguished from the prevention of complications or after-effects of existing disease. [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] Procollagen: A biosynthetic precursor of collagen containing additional amino acid sequences at the amino-terminal ends of the three polypeptide chains. Protocollagen, a precursor of procollagen consists of procollagen peptide chains in which proline and lysine have not yet been hydroxylated. [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

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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] Prophylaxis: An attempt to prevent disease. [NIH] Proportional: Being in proportion : corresponding in size, degree, or intensity, having the same or a constant ratio; of, relating to, or used in determining proportions. [EU] Propulsive: Tending or having power to propel; driving onward or forward; impelling to action or motion. [EU] Prospective Payment System: A system wherein reimbursement rates are set, for a given period of time, prior to the circumstances giving rise to actual reimbursement claims. [NIH] Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] Prostaglandin: Any of a group of components derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway that are extremely potent mediators of a diverse group of physiologic processes. The abbreviation for prostaglandin is PG; specific compounds are designated by adding one of the letters A through I to indicate the type of substituents found on the hydrocarbon skeleton and a subscript (1, 2 or 3) to indicate the number of double bonds in the hydrocarbon skeleton e.g., PGE2. The predominant naturally occurring prostaglandins all have two double bonds and are synthesized from arachidonic acid (5,8,11,14-eicosatetraenoic acid) by the pathway shown in the illustration. The 1 series and 3 series are produced by the same pathway with fatty acids having one fewer double bond (8,11,14-eicosatrienoic acid or one more double bond (5,8,11,14,17-eicosapentaenoic acid) than arachidonic acid. The subscript a or ß indicates the configuration at C-9 (a denotes a substituent below the plane of the ring, ß, above the plane). The naturally occurring PGF's have the a configuration, e.g., PGF2a. All of the prostaglandins act by binding to specific cell-surface receptors causing an increase in the level of the intracellular second messenger cyclic AMP (and in some cases cyclic GMP also). The effect produced by the cyclic AMP increase depends on the specific cell type. In some cases there is also a positive feedback effect. Increased cyclic AMP increases prostaglandin synthesis leading to further increases in cyclic AMP. [EU] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va

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and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. Quaternary protein structure describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Proteinuria: The presence of protein in the urine, indicating that the kidneys are not working properly. [NIH] Proteoglycans: Glycoproteins which have a very high polysaccharide content. [NIH] Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Proto-Oncogene Proteins: Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity. [NIH] Proto-Oncogene Proteins c-mos: Cellular proteins encoded by the c-mos genes. They function in the cell cycle to maintain maturation promoting factor in the active state and have protein-serine/threonine kinase activity. Oncogenic transformation can take place when c-mos proteins are expressed at the wrong time. [NIH] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] 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] Psychogenic: Produced or caused by psychic or mental factors rather than organic factors. [EU]

Psychology: The science dealing with the study of mental processes and behavior in man and animals. [NIH] Psychomotor: Pertaining to motor effects of cerebral or psychic activity. [EU] Psychotherapy: A generic term for the treatment of mental illness or emotional disturbances 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]

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Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]

Pulmonary: Relating to the lungs. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] Pulmonary Circulation: The circulation of blood through 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 hypertension: Abnormally high blood pressure in the arteries of the lungs. [NIH] Pulmonary Ventilation: The total volume of gas per minute inspired or expired measured in liters per minute. [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] Radioactive: Giving off radiation. [NIH] Radioimmunoassay: Classic quantitative assay for detection of antigen-antibody reactions using a radioactively labeled substance (radioligand) either directly or indirectly to measure the binding of the unlabeled substance to a specific antibody or other receptor system. Nonimmunogenic substances (e.g., haptens) can be measured if coupled to larger carrier proteins (e.g., bovine gamma-globulin or human serum albumin) capable of inducing antibody formation. [NIH] Radiological: Pertaining to radiodiagnostic and radiotherapeutic procedures, and interventional radiology or other planning and guiding medical radiology. [NIH] Radiopharmaceutical: Any medicinal product which, when ready for use, contains one or more radionuclides (radioactive isotopes) included for a medicinal purpose. [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

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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] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] Receptivity: The condition of the reproductive organs of a female flower that permits effective pollination. [NIH] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Receptors, Serotonin: Cell-surface proteins that bind serotonin and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Red blood cells: RBCs. Cells that carry oxygen to all parts of the body. Also called erythrocytes. [NIH] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Reflective: Capable of throwing back light, images, sound waves : reflecting. [EU] Reflex: An involuntary movement or exercise of function in a part, excited in response to a stimulus applied to the periphery and transmitted to the brain or spinal cord. [NIH] Reflux: The term used when liquid backs up into the esophagus from the stomach. [NIH]

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Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Refractive Power: The ability of an object, such as the eye, to bend light as light passes through it. [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] Rehabilitative: Instruction of incapacitated individuals or of those affected with some mental disorder, so that some or all of their lost ability may be regained. [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]

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Research Support: Financial support of research activities. [NIH] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Respirator: A mechanical device that helps a patient breathe; a mechanical ventilator. [NIH] Respiratory Muscles: These include the muscles of the diaphragm and the intercostal muscles. [NIH] Respiratory Physiology: Functions and activities of the respiratory tract as a whole or of any of its parts. [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] Restitution: The restoration to a normal state. [NIH] Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [NIH] Resuscitation: The restoration to life or consciousness of one apparently dead; it includes such measures as artificial respiration and cardiac massage. [EU] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] Retinal: 1. Pertaining to the retina. 2. The aldehyde of retinol, derived by the oxidative enzymatic splitting of absorbed dietary carotene, and having vitamin A activity. In the retina, retinal combines with opsins to form visual pigments. One isomer, 11-cis retinal combines with opsin in the rods (scotopsin) to form rhodopsin, or visual purple. Another, all-trans retinal (trans-r.); visual yellow; xanthopsin) results from the bleaching of rhodopsin by light, in which the 11-cis form is converted to the all-trans form. Retinal also combines with opsins in the cones (photopsins) to form the three pigments responsible for colour vision. Called also retinal, and retinene1. [EU] 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] Retrospective: Looking back at events that have already taken place. [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] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of

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developing a disease. [NIH] Risk patient: Patient who is at risk, because of his/her behaviour or because of the type of person he/she is. [EU] 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] 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] Saponin: A substance found in soybeans and many other plants. Saponins may help lower cholesterol and may have anticancer effects. [NIH] Sarcolemma: The plasma membrane of a smooth, striated, or cardiac muscle fiber. [NIH] Sarcomere: The repeating structural unit of a striated muscle fiber. [NIH] Sarcoplasmic Reticulum: A network of tubules and sacs in the cytoplasm of skeletal muscles that assist with muscle contraction and relaxation by releasing and storing calcium ions. [NIH] 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] Schizoid: Having qualities resembling those found in greater degree in schizophrenics; a person of schizoid personality. [NIH] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [NIH] Schizotypal Personality Disorder: A personality disorder in which there are oddities of thought (magical thinking, paranoid ideation, suspiciousness), perception (illusions, depersonalization), speech (digressive, vague, overelaborate), and behavior (inappropriate affect in social interactions, frequently social isolation) that are not severe enough to characterize schizophrenia. [NIH] Scleroderma: A chronic disorder marked by hardening and thickening of the skin. Scleroderma can be localized or it can affect the entire body (systemic). [NIH] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Second Messenger Systems: Systems in which an intracellular signal is generated in response to an intercellular primary messenger such as a hormone or neurotransmitter. They are intermediate signals in cellular processes such as metabolism, secretion, contraction, phototransduction, and cell growth. Examples of second messenger systems are the adenyl cyclase-cyclic AMP system, the phosphatidylinositol diphosphate-inositol triphosphate system, and the cyclic GMP system. [NIH]

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Secondary tumor: Cancer that has spread from the organ in which it first appeared to another organ. For example, breast cancer cells may spread (metastasize) to the lungs and cause the growth of a new tumor. When this happens, the disease is called metastatic breast cancer, and the tumor in the lungs is called a secondary tumor. Also called secondary cancer. [NIH] Secretin: A hormone made in the duodenum. Causes the stomach to make pepsin, the liver to make bile, and the pancreas to make a digestive juice. [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] Secular trends: A relatively long-term trend in a community or country. [NIH] 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] 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] 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 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]

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Serine Endopeptidases: Any member of the group of endopeptidases containing at the active site a serine residue involved in catalysis. EC 3.4.21. [NIH] Serologic: Analysis of a person's serum, especially specific immune or lytic serums. [NIH] Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (receptors, serotonin) explain the broad physiological actions and distribution of this biochemical mediator. [NIH] Serous: Having to do with serum, the clear liquid part of blood. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Serum Albumin: A major plasma protein that serves in maintaining the plasma colloidal osmotic pressure and transporting large organic anions. [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] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Simvastatin: A derivative of lovastatin and potent competitive inhibitor of 3-hydroxy-3methylglutaryl coenzyme A reductase (hydroxymethylglutaryl CoA reductases), which is the rate-limiting enzyme in cholesterol biosynthesis. It may also interfere with steroid hormone production. Due to the induction of hepatic LDL receptors, it increases breakdown of LDL-cholesterol (lipoproteins, LDL cholesterol). [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or

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cartilage. [NIH] Skin Aging: The process of aging due to changes in the structure and elasticity of the skin over time. It may be a part of physiological aging or it may be due to the effects of ultraviolet radiation, usually through exposure to sunlight. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Sleep apnea: A serious, potentially life-threatening breathing disorder characterized by repeated cessation of breathing due to either collapse of the upper airway during sleep or absence of respiratory effort. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]

Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Social 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] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solid tumor: Cancer of body tissues other than blood, bone marrow, or the lymphatic system. [NIH] 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] Somatostatin: A polypeptide hormone produced in the hypothalamus, and other tissues and organs. It inhibits the release of human growth hormone, and also modulates important physiological functions of the kidney, pancreas, and gastrointestinal tract. Somatostatin receptors are widely expressed throughout the body. Somatostatin also acts as a neurotransmitter in the central and peripheral nervous systems. [NIH] Sorbitol: A polyhydric alcohol with about half the sweetness of sucrose. Sorbitol occurs naturally and is also produced synthetically from glucose. It was formerly used as a diuretic and may still be used as a laxative and in irrigating solutions for some surgical procedures. It is also used in many manufacturing processes, as a pharmaceutical aid, and in several research applications. [NIH] Sound wave: An alteration of properties of an elastic medium, such as pressure, particle displacement, or density, that propagates through the medium, or a superposition of such

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alterations. [NIH] Spastic: 1. Of the nature of or characterized by spasms. 2. Hypertonic, so that the muscles are stiff and the movements awkward. 3. A person exhibiting spasticity, such as occurs in spastic paralysis or in cerebral palsy. [EU] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Sperm: The fecundating fluid of the male. [NIH] Sphenoid: An unpaired cranial bone with a body containing the sphenoid sinus and forming the posterior part of the medial walls of the orbits. [NIH] Sphenoidal: Relating or belonging to the sphenoid bone. [NIH] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spinal Nerves: The 31 paired peripheral nerves formed by the union of the dorsal and ventral spinal roots from each spinal cord segment. The spinal nerve plexuses and the spinal roots are also included. [NIH] Spleen: An organ that is part of the lymphatic system. The spleen produces lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side of the abdomen near the stomach. [NIH] 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] 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] 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] Sterile: Unable to produce children. [NIH] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU]

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Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]

Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stool: The waste matter discharged in a bowel movement; feces. [NIH] 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] Strophanthins: A number of different cardioactive glycosides obtained from Strophanthus species. ouabain is from S. gratus and cymarine from S. kombe. They are used like the digitalis glycosides. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subclavian: The direct continuation of the axillary vein at the lateral border of the first rib. It passes medially to join the internal jugular vein and form the brachiocephalic vein on each side. [NIH] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] 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] 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] Sudden cardiac death: Cardiac arrest caused by an irregular heartbeat. [NIH] Sudden death: Cardiac arrest caused by an irregular heartbeat. The term "death" is somewhat misleading, because some patients survive. [NIH] Sulfur: An element that is a member of the chalcogen family. It has an atomic symbol S, atomic number 16, and atomic weight 32.066. It is found in the amino acids cysteine and methionine. [NIH]

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Superoxide: Derivative of molecular oxygen that can damage cells. [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] 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 neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Synchrony: The normal physiologic sequencing of atrial and ventricular activation and contraction. [NIH] Synovial: Of pertaining to, or secreting synovia. [EU] 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 blood pressure: The maximum pressure in the artery produced as the heart

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contracts and blood begins to flow. [NIH] 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]

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] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] Tetany: 1. Hyperexcitability of nerves and muscles due to decrease in concentration of extracellular ionized calcium, which may be associated with such conditions as parathyroid hypofunction, vitamin D deficiency, and alkalosis or result from ingestion of alkaline salts; it is characterized by carpopedal spasm, muscular twitching and cramps, laryngospasm with inspiratory stridor, hyperreflexia and choreiform movements. 2. Tetanus. [EU] 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] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thermal: Pertaining to or characterized by heat. [EU] Thiamine: 3-((4-Amino-2-methyl-5-pyrimidinyl)methyl)-5-(2methylthiazolium chloride. [NIH]

hydroxyethyl)-4-

Thigh: A leg; in anatomy, any elongated process or part of a structure more or less comparable to a leg. [NIH] Thoracic: Having to do with the chest. [NIH] Thorax: A part of the trunk between the neck and the abdomen; the chest. [NIH] Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] 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]

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Thromboxanes: Physiologically active compounds found in many organs of the body. They are formed in vivo from the prostaglandin endoperoxides and cause platelet aggregation, contraction of arteries, and other biological effects. Thromboxanes are important mediators of the actions of polyunsaturated fatty acids transformed by cyclooxygenase. [NIH] Thrombus: An aggregation of blood factors, primarily platelets and fibrin with entrapment of cellular elements, frequently causing vascular obstruction at the point of its formation. Some authorities thus differentiate thrombus formation from simple coagulation or clot formation. [EU] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Thyroid Gland: A highly vascular endocrine gland consisting of two lobes, one on either side of the trachea, joined by a narrow isthmus; it produces the thyroid hormones which are concerned in regulating the metabolic rate of the body. [NIH] Thyroid Hormones: Hormones secreted by the thyroid gland. [NIH] Thyrotropin: A peptide hormone secreted by the anterior pituitary. It promotes the growth of the thyroid gland and stimulates the synthesis of thyroid hormones and the release of thyroxine by the thyroid gland. [NIH] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH] 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] Tin: A trace element that is required in bone formation. It has the atomic symbol Sn, atomic number 50, and atomic weight 118.71. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tissue Plasminogen Activator: A proteolytic enzyme in the serine protease family found in many tissues which converts plasminogen to plasmin. It has fibrin-binding activity and is immunologically different from urinary plasminogen activator. The primary sequence, composed of 527 amino acids, is identical in both the naturally occurring and synthetic proteases. EC 3.4.21.68. [NIH] Tolazamide: A sulphonylurea hypoglycemic agent with actions and uses similar to those of chlorpropamide. [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] 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

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toxic manifestations. [NIH] Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [NIH] Trace element: Substance or element essential to plant or animal life, but present in extremely small amounts. [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] 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] Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [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]

Triage: The sorting out and classification of patients or casualties to determine priority of need and proper place of treatment. [NIH] Triglyceride: A lipid carried through the blood stream to tissues. Most of the body's fat tissue is in the form of triglycerides, stored for use as energy. Triglycerides are obtained primarily from fat in foods. [NIH] 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]

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Tumor marker: A substance sometimes found in an increased amount in the blood, other body fluids, or tissues and which may mean that a certain type of cancer is in the body. Examples of tumor markers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and gastrointestinal tract cancers), and PSA (prostate cancer). Also called biomarker. [NIH] Tumor Necrosis Factor: Serum glycoprotein produced by activated macrophages and other mammalian mononuclear leukocytes which has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. It mimics the action of endotoxin but differs from it. It has a molecular weight of less than 70,000 kDa. [NIH] 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] Ulcerative colitis: Chronic inflammation of the colon that produces ulcers in its lining. This condition is marked by abdominal pain, cramps, and loose discharges of pus, blood, and mucus from the bowel. [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]

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Urinary Plasminogen Activator: A proteolytic enzyme that converts plasminogen to plasmin where the preferential cleavage is between arginine and valine. It was isolated originally from human urine, but is found in most tissues of most vertebrates. EC 3.4.21.73. [NIH]

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] 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] 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] Vaccination: Administration of vaccines to stimulate the host's immune response. This includes any preparation intended for active immunological prophylaxis. [NIH] Vaccine: A substance or group of substances meant to cause the immune system to respond 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] 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]

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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] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venous: Of or pertaining to the veins. [EU] Venous blood: Blood that has given up its oxygen to the tissues and carries carbon dioxide back for gas exchange. [NIH] Venous Pressure: The blood pressure in a vein. It is usually measured to assess the filling pressure to the ventricle. [NIH] Ventilation: 1. In respiratory physiology, the process of exchange of air between the lungs and the ambient air. Pulmonary ventilation (usually measured in litres per minute) refers to the total exchange, whereas alveolar ventilation refers to the effective ventilation of the alveoli, in which gas exchange with the blood takes place. 2. In psychiatry, verbalization of one's emotional problems. [EU] Ventilator: A breathing machine that is used to treat respiratory failure by promoting ventilation; also called a respirator. [NIH] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Ventricular: Pertaining to a ventricle. [EU] Ventricular Dysfunction: A condition in which the ventricles of the heart exhibit a decreased functionality. [NIH] Ventricular Function: The hemodynamic and electrophysiological action of the ventricles. [NIH]

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] 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 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] 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

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tissues of the host. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Viscera: Any of the large interior organs in any one of the three great cavities of the body, especially in the abdomen. [NIH] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] Visceral Afferents: The sensory fibers innervating the viscera. [NIH] Viscosity: A physical property of fluids that determines the internal resistance to shear forces. [EU] 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] Wakefulness: A state in which there is an enhanced potential for sensitivity and an efficient responsiveness to external stimuli. [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]

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] Womb: A hollow, thick-walled, muscular organ in which the impregnated ovum is developed into a child. [NIH] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Xanthine: An urinary calculus. [NIH] Xanthine Oxidase: An iron-molybdenum flavoprotein containing FAD that oxidizes hypoxanthine, some other purines and pterins, and aldehydes. Deficiency of the enzyme, an autosomal recessive trait, causes xanthinuria. EC 1.1.3.22. [NIH] Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] Yolk Sac: An embryonic membrane formed from endoderm and mesoderm. In reptiles and birds it incorporates the yolk into the digestive tract for nourishing the embryo. In placental mammals its nutritional function is vestigial; however, it is the source of most of the

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intestinal mucosa and the site of formation of the germ cells. It is sometimes called the vitelline sac, which should not be confused with the vitelline membrane of the egg. [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]

341

INDEX 1 1-phosphate, 197, 257, 316 A Abdomen, 200, 257, 267, 268, 298, 302, 315, 330, 331, 333, 337, 339 Abdominal, 52, 200, 257, 258, 274, 280, 288, 299, 313, 315, 319, 324, 335, 336 Abdominal Pain, 257, 288, 299, 336 Aberrant, 58, 257 Abscess, 257, 327 Acceptor, 257, 301, 313 Accommodation, 257, 308 Acetohexamide, 181, 257 Acetylcholine, 34, 257, 310 Acidosis, 210, 211, 257, 279 Actin, 9, 37, 182, 257, 289, 307, 308, 335 Activities of Daily Living, 19, 257 Acute renal, 210, 257, 292 Acyl, 50, 167, 198, 257 Adaptability, 190, 257, 271, 272 Adaptation, 35, 47, 56, 154, 257, 317 Adenosine, 257, 260, 295, 316 Adenovirus, 8, 59, 125, 258 Adipocytes, 258, 275, 301 Adipose Tissue, 10, 258 Adjunctive Therapy, 174, 258 Adjustment, 210, 257, 258 Adrenal Cortex, 258, 259, 277, 319, 324 Adrenal Glands, 258, 261, 324 Adrenal insufficiency, 208, 209, 258 Adrenal Medulla, 258, 271, 285, 311 Adrenaline, 139, 258 Adrenergic Agents, 169, 258 Adrenergic Agonists, 169, 258 Adrenergic Antagonists, 24, 169, 193, 258 Adverse Effect, 18, 258, 328 Aerobic, 53, 258, 286, 306 Aerobic Exercise, 53, 258 Aetiology, 102, 258 Afferent, 26, 258, 301 Affinity, 59, 171, 258, 259, 301, 329 Afterload, 259, 277 Agar, 259, 317 Age of Onset, 259, 336 Agonist, 40, 176, 183, 259, 279, 281 Air Sacs, 200, 259, 260 Airway, 13, 74, 187, 188, 259, 329 Akinesia, 57, 259

Albumin, 4, 32, 95, 259, 305, 317 Aldehydes, 259, 339 Aldosterone, 16, 62, 68, 89, 104, 105, 171, 176, 194, 259 Aldosterone Antagonists, 104, 259 Alendronate, 183, 259 Algorithms, 179, 259, 267 Alkaline, 257, 259, 269, 333 Alkaloid, 259, 266 Alkalosis, 169, 210, 259, 333 Allantois, 260, 287 Alleles, 27, 260 Allergen, 260, 279 Allergic Rhinitis, 168, 260 Allogeneic, 195, 260, 291 Allopurinol, 64, 65, 260 Alpha-1, 68, 83, 96, 176, 260, 316, 319 Alprenolol, 260, 305 Alternative medicine, 222, 260 Alveoli, 200, 260, 338 Amino Acid Sequence, 184, 260, 262, 319 Amino Acids, 131, 260, 262, 264, 270, 314, 318, 321, 327, 331, 334, 336 Amino-terminal, 260, 319 Amiodarone, 95, 196, 226, 260 Amnion, 260, 287 Amrinone, 260, 306 Amyloidosis, 129, 210, 260 Anabolic, 154, 261, 280 Anabolic Steroids, 154, 261 Anaesthesia, 261, 296 Anal, 65, 261, 284, 302, 307 Analgesic, 210, 261 Analog, 145, 261, 311 Analogous, 184, 261, 335 Analytes, 238, 261 Anaphylatoxins, 261, 275 Anaphylaxis, 180, 261 Anatomical, 62, 261, 265, 268, 275, 280, 296, 326 Anemia, 68, 69, 84, 114, 116, 208, 261, 292 Anesthesia, 180, 211, 259, 261, 283, 319 Anesthetics, 261, 285 Aneurysm, 48, 261, 337 Angina, 33, 153, 168, 180, 192, 193, 197, 209, 211, 244, 261, 262, 267, 305, 310 Angina Pectoris, 180, 192, 193, 197, 209, 261, 267, 305

342 Congestive Heart Failure

Angiocardiography, 78, 261 Angiogenesis, 47, 178, 197, 261, 304 Angioplasty, 39, 122, 168, 197, 209, 262, 308 Angiotensin converting enzyme inhibitor, 192, 262 Angiotensin-Converting Enzyme Inhibitors, 68, 83, 262 Angiotensinogen, 193, 204, 262, 324 Animal model, 7, 9, 23, 32, 35, 52, 54, 145, 262 Anions, 259, 262, 299, 328 Anorexia, 177, 197, 262, 288 Antagonism, 89, 141, 262, 280 Antecedent, 63, 83, 262 Anterior Cerebral Artery, 262, 272 Anthracycline, 34, 124, 165, 262 Antianginal, 260, 262 Antiarrhythmic, 102, 260, 262 Antibiotic, 262, 314, 333 Antibodies, 26, 177, 262, 265, 285, 291, 292, 293, 303, 307, 317 Antibody, 26, 34, 58, 104, 170, 259, 262, 263, 274, 291, 293, 296, 304, 307, 322, 330 Anticoagulant, 262, 320 Antidiabetic, 263, 290 Antidiuretic, 263, 309 Antidote, 263, 269 Antigen, 170, 259, 261, 262, 263, 274, 285, 293, 294, 296, 304, 322 Antigen-Antibody Complex, 263, 274 Antihypertensive, 153, 211, 260, 263 Anti-inflammatory, 263, 264 Anti-Inflammatory Agents, 263, 264 Antioxidant, 41, 49, 52, 153, 263, 264, 313 Antiviral, 263, 314 Antrectomy, 263, 266 Anuria, 263, 300 Anus, 261, 263, 268 Anxiety, 159, 175, 193, 197, 254, 263 Anxiety Disorders, 175, 263 Aorta, 163, 194, 263, 276, 292, 324, 338 Apnea, 69, 188, 204, 254, 263 Apoptosis, 47, 111, 263 Aqueous, 263, 266, 278, 294 Arachidonic Acid, 25, 263, 301, 320 Arginine, 10, 33, 131, 156, 261, 263, 310, 337 Aromatic, 264, 270, 316 Arrhythmia, 28, 78, 79, 129, 196, 223, 238, 262, 264, 338 Arteriolar, 81, 264, 268, 324

Arterioles, 264, 267, 269, 306, 308, 337 Arteriosclerosis, 264, 294 Arteriosus, 264, 322 Arteriovenous, 34, 66, 74, 264, 306 Arteriovenous Fistula, 34, 66, 74, 264 Articular, 264, 301, 312 Ascites, 176, 264 Ascorbic Acid, 119, 180, 264, 294 Aspartic, 264, 283 Aspartic Endopeptidases, 264, 283 Aspirin, 40, 80, 83, 209, 264 Assay, 9, 12, 57, 59, 109, 264, 322 Asymptomatic, 17, 40, 45, 215, 242, 264 Atherogenic, 26, 264 Atrial Fibrillation, 73, 95, 125, 192, 193, 196, 264 Atrial Flutter, 193, 264 Atrial Natriuretic Factor, 171, 264 Atrioventricular, 99, 264, 265, 332 Atrioventricular Node, 265, 332 Atrium, 166, 171, 184, 188, 264, 265, 306, 332, 338 Atrophy, 50, 265, 310 Auditory, 265, 291, 304, 337 Autoantibodies, 26, 265 Autoantigens, 265 Autoimmune disease, 12, 167, 187, 265, 307 Autologous, 142, 145, 157, 195, 265 Autonomic, 35, 43, 175, 257, 265, 311, 315, 332 Autonomic Nervous System, 265, 315, 332 Axillary, 265, 331 Axillary Vein, 265, 331 Axons, 265, 312, 315 B Bacteria, 257, 262, 263, 265, 266, 279, 283, 284, 285, 286, 292, 306, 317, 323, 327, 335, 337 Bacterial Physiology, 257, 265 Bactericidal, 265, 285 Bacteriophage, 265, 317, 335 Bacterium, 265, 292 Bacteriuria, 265, 336 Basal Ganglia, 266, 268 Basal Ganglia Diseases, 266 Base, 42, 90, 115, 117, 147, 187, 259, 266, 278, 279, 285, 299, 300, 333 Basement Membrane, 177, 266, 286, 300 Benign, 168, 197, 266, 291, 309 Benzoic Acid, 181, 266 Berberine, 81, 266

Index 343

Beta blocker, 40, 75, 95, 266 Bilateral, 266, 335 Bile, 186, 266, 288, 293, 302, 327, 330 Bile Acids, 186, 266, 288, 330 Bile Acids and Salts, 266 Biliopancreatic Diversion, 115, 117, 266 Bilirubin, 162, 259, 266 Bioavailability, 40, 49, 156, 176, 266 Biochemical, 17, 18, 35, 37, 49, 56, 60, 63, 165, 203, 260, 266, 300, 312, 328 Biological Markers, 153, 266 Biological therapy, 267, 291 Biomarkers, 24, 39, 62, 82, 96, 267 Biomechanics, 61, 267 Biophysics, 33, 48, 49, 54, 267 Biopsy, 267, 314 Biosynthesis, 259, 263, 267, 302, 316, 327, 328 Biotechnology, 65, 66, 214, 222, 233, 267 Bisoprolol, 71, 192, 193, 267 Bladder, 168, 211, 267, 277, 296, 307, 310, 320, 324, 336, 337 Bloating, 254, 267, 299 Blood Cell Count, 267, 292 Blood Coagulation, 267, 269, 333 Blood Glucose, 211, 244, 267, 292, 295, 297 Blood Platelets, 267, 328 Blot, 12, 34, 267 Body Fluids, 259, 267, 269, 282, 287, 311, 329, 336 Body Mass Index, 268, 312 Body Regions, 268, 274 Bolus, 114, 117, 124, 268 Bolus infusion, 268 Bone Marrow, 31, 268, 296, 303, 307, 329 Bowel, 177, 261, 268, 280, 284, 297, 298, 300, 311, 315, 331, 336 Bowel Movement, 268, 280, 331 Brachial, 265, 268, 304 Brachial Plexus, 268, 304 Bradycardia, 161, 179, 268 Bradykinin, 34, 114, 115, 116, 117, 268, 299, 310, 317 Brain Hypoxia, 268 Brain Infarction, 268 Brain Ischemia, 32, 268 Branch, 109, 175, 251, 268, 283, 289, 303, 304, 312, 314, 321, 324, 330, 333 Breakdown, 268, 279, 280, 288, 312, 328 Bromine, 191, 268 Bronchi, 268, 285, 335 Bronchioles, 260, 268

Bronchitis, 168, 268, 273 Bulimia, 197, 269 Bundle-Branch Block, 93, 269 Bypass, 56, 209, 269, 299, 308 C Cachexia, 177, 183, 269 Calcineurin, 56, 269 Calcium Carbonate, 201, 269 Calcium channel blocker, 269, 338 Calcium Chloride, 201, 269 Calcium Hydroxide, 201, 269 Calmodulin, 269, 297 Calpain, 204, 269 Capillary, 200, 260, 268, 269, 289, 338 Capillary Permeability, 268, 269 Capsules, 270, 281, 289 Captopril, 103, 114, 116, 218, 270 Carbohydrate, 20, 22, 50, 270, 290, 318 Carbon Dioxide, 158, 200, 269, 270, 272, 273, 288, 294, 295, 317, 325, 338 Carboxy, 152, 156, 198, 270 Carboxylic Acids, 186, 270 Carcinogenic, 270, 297, 320, 330 Cardenolides, 96, 270 Cardiac arrest, 77, 270, 331 Cardiac Glycosides, 169, 270 Cardiac Output, 25, 38, 154, 155, 157, 161, 163, 164, 174, 175, 179, 185, 198, 270, 292, 331 Cardiogenic, 161, 215, 270 Cardiomyoplasty, 157, 270 Cardiopulmonary, 65, 109, 110, 270 Cardiorespiratory, 258, 270 Cardioselective, 267, 270 Cardiotonic, 260, 271, 280, 281, 306 Cardiotoxic, 165, 271 Cardiotoxicity, 78, 271 Cardiovascular disease, 8, 9, 12, 20, 21, 22, 23, 35, 40, 45, 115, 118, 152, 176, 203, 211, 271 Cardiovascular System, 193, 194, 271 Carnitine, 50, 119, 120, 271 Carotene, 271, 325 Carpal Tunnel Syndrome, 204, 271 Carrier Proteins, 271, 317, 322 Case report, 67, 74, 89, 94, 271, 273 Case series, 271, 273 Catecholamine, 8, 179, 271, 279, 281, 316 Catheterization, 24, 43, 140, 255, 262, 271, 298, 308, 338 Catheters, 179, 200, 271 Causal, 48, 58, 223, 271, 284, 292

344 Congestive Heart Failure

Cause of Death, 21, 40, 169, 208, 271 Cell Death, 47, 165, 263, 271, 309 Cell Differentiation, 271, 328 Cell Division, 265, 272, 291, 306, 317 Cell membrane, 181, 208, 271, 272, 279, 297, 316 Cell proliferation, 264, 272, 328 Cell Respiration, 272, 306, 325 Cell Survival, 272, 291 Centrifugation, 272, 292 Cerebral, 32, 199, 262, 266, 268, 272, 278, 285, 288, 294, 321, 330 Cerebral Infarction, 32, 268, 272, 294 Cerebrovascular, 54, 266, 271, 272 Cerebrum, 272 Cervical, 268, 272, 304 Character, 261, 272, 278 Chemoreceptors, 13, 272 Chemotactic Factors, 272, 275 Chemotaxis, 152, 272 Chest Pain, 209, 244, 272 Chlorine, 191, 272 Cholecystectomy, 67, 273 Cholecystokinin, 182, 273 Cholesterol, 4, 83, 183, 186, 192, 209, 239, 244, 266, 273, 276, 282, 294, 301, 302, 326, 328, 330 Chorion, 273, 287 Chromatin, 263, 273 Chromosomal, 273, 317 Chromosome, 27, 273, 301 Chronic Disease, 87, 161, 215, 269, 273 Chronic Obstructive Pulmonary Disease, 6, 11, 168, 180, 188, 273 Chronic renal, 68, 114, 116, 208, 209, 210, 273, 288, 318 Circulatory system, 55, 179, 273 CIS, 12, 50, 181, 273, 325 Citric Acid, 50, 273 Citric Acid Cycle, 50, 273 Citrus, 264, 273 Clamp, 25, 35, 273 Clinical Medicine, 273, 319 Clinical study, 122, 142, 273, 276 Clitoral, 168, 274 Cloning, 10, 27, 198, 267, 274 Coenzyme, 122, 131, 264, 274, 302, 328 Cofactor, 274, 321, 333 Colic, 180, 274 Colitis, 274, 299 Collagen, 16, 34, 39, 48, 266, 274, 286, 287, 288, 304, 317, 319, 320

Collagenases, 177, 274 Collapse, 55, 188, 261, 268, 274, 329 Colloidal, 259, 274, 328 Combination Therapy, 176, 211, 274 Complement, 179, 261, 274, 275, 289, 303, 317 Complementary and alternative medicine, 121, 133, 275 Complementary medicine, 121, 275 Complete remission, 275, 324 Computational Biology, 233, 275 Concomitant, 41, 161, 183, 275 Conduction, 27, 161, 179, 202, 265, 269, 275 Cone, 275, 299 Confusion, 275, 281, 295, 336 Congestion, 159, 176, 200, 275 Conjugated, 40, 266, 275, 277, 311 Conjunctiva, 275, 297 Connective Tissue, 177, 264, 268, 274, 275, 287, 288, 302, 305, 315, 325, 332 Connective Tissue Cells, 275 Consciousness, 261, 275, 278, 281, 325 Constipation, 275, 299 Constitutional, 275, 308 Constriction, 275, 299, 337 Constriction, Pathologic, 275, 337 Consultation, 189, 276, 286 Consumption, 42, 68, 127, 242, 276, 279, 288, 313 Contractile Proteins, 9, 198, 276 Contractility, 7, 8, 9, 26, 35, 55, 64, 124, 162, 165, 185, 190, 198, 202, 208, 262, 276, 282 Contraindications, ii, 276 Control group, 4, 6, 7, 13, 14, 30, 147, 224, 276, 319, 322 Controlled clinical trial, 42, 67, 121, 140, 276 Controlled study, 6, 70, 122, 276 Conus, 276, 322 Coordination, 276, 307 Cornea, 276 Corneal Ulcer, 178, 276 Coronary Angiography, 209, 276 Coronary Arteriosclerosis, 276, 308 Coronary Artery Bypass, 15, 276 Coronary Circulation, 261, 276, 310 Coronary heart disease, 20, 30, 180, 186, 243, 271, 276 Coronary Thrombosis, 276, 305, 308 Corpus, 165, 276, 314, 319, 327

Index 345

Corpus Luteum, 276, 319 Cortex, 277, 285 Cortical, 176, 277, 286, 327 Cortisol, 259, 277 Counterpulsation, 70, 277 Cranial, 277, 291, 315, 330, 337 Creatine, 17, 119, 120, 123, 128, 136, 277 Creatine Kinase, 17, 136, 277 Creatinine, 4, 162, 255, 277, 300 Critical Care, 69, 71, 83, 94, 98, 99, 105, 127, 277 Cultured cells, 56, 277 Curative, 277, 333 Cutaneous, 211, 277, 302 Cyclic, 34, 165, 168, 269, 277, 291, 310, 316, 320, 326 Cysteine, 269, 277, 283, 331 Cysteine Endopeptidases, 277, 283 Cystitis, 180, 277 Cytochrome, 277, 313 Cytokine, 12, 21, 32, 57, 58, 177, 277, 298 Cytoplasm, 263, 272, 276, 277, 278, 291, 297, 307, 308, 326 Cytoskeletal Proteins, 269, 278 Cytoskeleton, 98, 278, 306 Cytotoxic, 57, 278, 298, 328 D Dairy Products, 201, 278, 326 Data Collection, 42, 63, 278, 287 Databases, Bibliographic, 233, 278 De novo, 23, 278 Decompensation, 9, 16, 23, 56, 140, 278 Degenerative, 177, 197, 276, 278, 303, 307, 312, 325 Deletion, 37, 50, 263, 278 Delirium, 197, 278 Delivery of Health Care, 278, 291 Dementia, 168, 197, 204, 278 Demyelinating Diseases, 178, 278 Dendrites, 278, 310 Density, 21, 33, 60, 183, 268, 272, 279, 282, 301, 312, 329 Dental Caries, 279, 287 Depolarization, 166, 172, 179, 279, 328 Depressive Disorder, 44, 54, 279, 302 Deprivation, 204, 279 Desensitization, 169, 279 Desmin, 58, 279 Deuterium, 279, 294 Developed Countries, 64, 279 Dexfenfluramine, 223, 279 DHEA, 132, 279

Diabetes Insipidus, 10, 279 Diabetes Mellitus, 6, 30, 41, 52, 129, 186, 208, 210, 211, 279, 280, 290, 292, 311 Diabetes, Gestational, 210, 279, 319 Diabetic Foot, 211, 279 Diabetic Ketoacidosis, 210, 279 Diabetic Retinopathy, 178, 180, 193, 280 Diagnostic procedure, 38, 151, 222, 280 Dialyzer, 280, 292 Diaphragm, 136, 280, 318, 325 Diarrhea, 266, 280, 299 Diastole, 62, 156, 280, 319 Diastolic blood pressure, 106, 280 Diastolic pressure, 48, 161, 184, 243, 277, 280, 294 Dietitian, 4, 280 Diffusion, 270, 280, 297, 336 Digestion, 266, 268, 280, 298, 302, 331 Digestive system, 148, 280 Digitalis, 4, 77, 104, 123, 161, 270, 280, 331 Dihydrotestosterone, 280, 323 Dilatation, 27, 36, 62, 141, 189, 261, 262, 280, 319, 337, 338 Dilatation, Pathologic, 280, 337 Dilate, 154, 280 Dilated cardiomyopathy, 27, 28, 36, 42, 58, 61, 64, 65, 81, 104, 110, 166, 202, 280 Dilation, 23, 36, 47, 154, 164, 168, 268, 280, 294, 337 Dilator, 95, 280, 310 Diltiazem, 79, 280 Dimerization, 59, 280 Direct, iii, 10, 21, 24, 31, 48, 50, 61, 147, 154, 159, 225, 244, 273, 281, 323, 331, 332 Disease Progression, 153, 154, 281 Disinfectant, 281, 285 Disorientation, 275, 278, 281 Disposition, 10, 281 Dissection, 281, 335 Dissociation, 77, 114, 116, 161, 258, 281 Dissociative Disorders, 281 Distal, 15, 163, 168, 176, 194, 202, 276, 281, 282, 288, 299, 321 Diuresis, 171, 281 Diuretic, 15, 77, 96, 101, 171, 191, 194, 269, 281, 288, 299, 329 Dobutamine, 79, 95, 107, 110, 281 Dosage Forms, 157, 281 Dose-dependent, 9, 64, 281 Drive, ii, vi, 4, 13, 15, 47, 113, 175, 207, 209, 210, 281 Drug Interactions, 227, 228, 281

346 Congestive Heart Failure

Drug Resistance, 209, 281, 282 Drug Tolerance, 281, 282, 334 Duct, 10, 66, 271, 282, 286, 326 Duke, 6, 24, 44, 53, 54, 114, 116, 282 Duodenum, 266, 282, 299, 313, 327, 331 Dwarfism, 183, 282 Dyskinesia, 282 Dyslipidemia, 211, 282 Dysmenorrhoea, 168, 282 Dysphoric, 279, 282 Dyspnea, 109, 128, 198, 254, 278, 282 Dystrophy, 27, 130, 282 E Echocardiography, 29, 32, 43, 48, 53, 57, 79, 97, 143, 255, 282, 338 Ectopic, 26, 282 Effector, 257, 274, 282, 310, 316 Effector cell, 282, 310 Efficacy, 5, 14, 18, 21, 29, 30, 32, 53, 55, 57, 58, 61, 81, 114, 116, 122, 124, 135, 140, 141, 142, 143, 144, 145, 153, 154, 158, 173, 197, 282, 335 Effusion, 200, 282 Ejection fraction, 13, 20, 32, 40, 57, 64, 162, 164, 282 Elasticity, 154, 264, 276, 282, 329 Elastin, 274, 282, 286 Elective, 105, 282 Electrocardiogram, 143, 282 Electrode, 166, 202, 282 Electrolyte, 90, 115, 117, 169, 194, 210, 259, 278, 283, 287, 292, 300, 311, 318, 329 Electrons, 263, 266, 283, 299, 303, 313, 314, 322 Electrophysiological, 60, 81, 203, 283, 338 Elementary Particles, 283, 303, 321 Embolus, 283, 296 Embryo, 260, 272, 283, 287, 296, 339 Emergency Medicine, 71, 75, 82, 104, 283 Emergency Treatment, 283 Emphysema, 159, 273, 283 Empirical, 140, 283 Enalapril, 42, 74, 283 Endarterectomy, 262, 283 Endocarditis, 208, 209, 253, 283 Endocardium, 283 Endometrium, 283, 305 Endopeptidases, 177, 264, 277, 283, 305, 314, 328 Endothelial cell, 22, 33, 111, 283, 284, 333 Endothelium, 22, 167, 168, 284, 310 Endothelium, Lymphatic, 284

Endothelium, Vascular, 284 Endothelium-derived, 167, 168, 284, 310 Endotoxic, 284, 301 Endotoxin, 284, 336 End-stage renal, 3, 208, 273, 284, 318 Energy balance, 13, 38, 284, 301 Enhancer, 51, 284 Enterocolitis, 64, 284 Environmental Exposure, 267, 284 Environmental Health, 232, 234, 284 Enzymatic, 41, 269, 271, 274, 279, 284, 325 Enzyme Inhibitors, 69, 165, 192, 284, 317 Epidemic, 13, 30, 46, 54, 211, 284, 330 Epidemiologic Studies, 267, 284 Epidemiological, 4, 39, 208, 284 Epidermal, 164, 284, 304 Epidermal Growth Factor, 164, 284 Epidermis, 284, 285 Epinephrine, 194, 258, 285, 311, 336 Epithelial, 176, 276, 285, 300 Epithelial Cells, 176, 285, 300 Epithelium, 266, 284, 285 Epitopes, 26, 285 Erectile, 180, 211, 285, 314 Erection, 169, 285 Erythrocytes, 261, 267, 268, 269, 285, 292, 323 Escalation, 32, 285 Esophageal, 285, 288 Esophagitis, 285, 288 Esophagus, 280, 285, 288, 302, 316, 323, 331 Estrogen, 183, 285 Ethanol, 24, 285 Eukaryotic Cells, 278, 285, 312, 336 Euthanasia, 124, 285 Evacuation, 275, 285, 300, 322 Evoke, 43, 285, 331 Excipients, 172, 285 Excitation, 7, 24, 28, 35, 38, 60, 179, 264, 286 Excitatory, 175, 286, 290 Excrete, 263, 286, 300 Exercise Test, 42, 110, 143, 162, 286 Exercise Tolerance, 6, 7, 17, 68, 83, 128, 286 Exhaustion, 262, 286 Exocrine, 273, 286, 313 Exogenous, 29, 55, 183, 270, 286, 336 Expert Systems, 286, 288 Expiration, 60, 187, 286, 325 Expiratory, 158, 187, 286

Index 347

Extracellular Matrix, 20, 37, 61, 62, 94, 194, 275, 286, 287, 304 Extracellular Matrix Proteins, 286, 304 Extracellular Space, 16, 208, 286, 306 Extracorporeal, 38, 199, 286, 292 Extremity, 211, 268, 286, 304 Eye Infections, 258, 286 F Family Planning, 233, 287 Fatigue, 19, 25, 173, 174, 198, 254, 287, 292 Fatty acids, 20, 50, 183, 259, 270, 279, 287, 320, 334 Femoral, 195, 287 Femur, 287 Fenfluramine, 223, 279, 287 Fetal Membranes, 178, 287 Fetus, 287, 317, 337 Fibrillation, 160, 287 Fibrin, 267, 287, 317, 333, 334 Fibroblasts, 49, 275, 287, 298 Fibrosis, 153, 168, 197, 287, 326 Fistula, 49, 287, 311 Flatus, 287, 288 Fluid Therapy, 287, 311 Fluorine, 191, 287 Foam Cells, 26, 287 Focus Groups, 19, 287 Fold, 64, 165, 185, 196, 287 Foot Ulcer, 211, 279, 287 Forearm, 267, 287, 304 Free Radical Scavengers, 26, 287 Friction, 288, 302 Frontal Lobe, 262, 272, 288 Fructose, 288, 293, 298 Fungistatic, 266, 288 Furosemide, 105, 114, 117, 124, 126, 288 Fuzzy Logic, 125, 288 G Gallbladder, 257, 273, 280, 288 Ganglia, 257, 266, 288, 309, 315, 332 Gas, 85, 109, 187, 270, 272, 280, 287, 288, 294, 299, 310, 311, 322, 325, 338 Gas exchange, 85, 109, 288, 325, 338 Gastric, 182, 271, 281, 285, 288 Gastric Acid, 182, 288 Gastrin, 182, 288, 293 Gastroenteritis, 268, 288 Gastroesophageal Reflux, 204, 288 Gastroesophageal Reflux Disease, 204, 288 Gastrointestinal, 22, 169, 182, 193, 204, 208, 211, 268, 273, 285, 288, 301, 328, 329, 331, 336

Gastrointestinal tract, 193, 204, 285, 288, 301, 328, 329, 336 Gelatin, 288, 289, 290, 333 Gelatinases, 177, 289 Gelsolin, 37, 289 Gene Expression, 23, 52, 65, 92, 115, 117, 289 General practitioner, 19, 289 Generator, 155, 159, 289 Genetic Counseling, 210, 289 Genetic Engineering, 267, 274, 289 Genetic Markers, 20, 28, 289 Genital, 168, 289, 337 Genitourinary, 193, 289, 337 Genitourinary system, 193, 289 Genomics, 31, 65, 198, 289 Genotype, 289, 316 Geriatric, 83, 115, 118, 189, 211, 289 Ginseng, 130, 131, 133, 289 Gland, 258, 289, 302, 313, 317, 320, 327, 331, 334 Gliclazide, 181, 289 Glipizide, 181, 289 Glomerular, 171, 178, 193, 210, 289, 290, 298, 300, 324 Glomerular Filtration Rate, 171, 289, 300 Glomeruli, 290 Glomerulonephritis, 193, 290 Glomerulosclerosis, 180, 290 Glomerulus, 171, 289, 290, 309 Glucokinase, 290, 293 Glucose Intolerance, 142, 279, 290 Glucose tolerance, 143, 180, 279, 290, 319 Glucose Tolerance Test, 290 Glutamate, 152, 290, 305 Glyburide, 181, 290 Glycine, 203, 266, 290, 327 Glycolysis, 11, 29, 290 Glycoprotein, 290, 300, 333, 336 Goats, 278, 290 Gonadal, 290, 330 Governing Board, 290, 318 Gp120, 290, 314 Graft, 170, 177, 196, 290, 291, 293, 296, 308 Graft Rejection, 170, 177, 196, 291, 296 Grafting, 56, 209, 276, 291, 296 Granulocytes, 291, 301, 328, 339 Gravis, 180, 204, 291 Growth factors, 199, 291 Guanylate Cyclase, 291, 310 H Hair Cells, 291, 304

348 Congestive Heart Failure

Haplotypes, 20, 291 Haptens, 259, 291, 322 Headache, 291, 294, 295, 297, 319 Health Care Costs, 59, 291 Health Expenditures, 291 Health Services, 44, 74, 147, 278, 291 Health Status, 63, 86, 143, 291 Heart attack, 154, 175, 186, 217, 223, 243, 244, 271, 291 Heart Catheterization, 162, 292 Heart Transplantation, 51, 145, 162, 170, 196, 292 Heart Valves, 166, 292 Heartbeat, 166, 174, 182, 292, 331 Hematocrit, 171, 267, 292 Hematuria, 210, 292 Heme, 266, 277, 292 Hemochromatosis, 223, 292 Hemodiafiltration, 292, 336 Hemodialysis, 4, 210, 269, 280, 292, 300, 336 Hemodynamics, 37, 67, 160, 208, 292 Hemofiltration, 210, 292, 336 Hemoglobin, 261, 267, 285, 292 Hemolysis, 38, 292 Hemolytic, 210, 292 Hemorrhage, 32, 180, 291, 293, 308, 331, 333, 339 Hemostasis, 293, 328 Hepatic, 168, 259, 278, 290, 293, 328 Hereditary, 210, 293, 307, 309 Heredity, 242, 243, 289, 293 Heterogeneity, 27, 259, 293 Hexokinase, 50, 293 Hibernation, 87, 127, 293 Homeostasis, 10, 35, 183, 186, 293 Homologous, 184, 260, 293, 332 Hormonal, 12, 26, 52, 88, 168, 193, 265, 293 Hormone Replacement Therapy, 209, 293, 319 Hormone therapy, 87, 293 Hospice, 18, 293 Host, 265, 293, 295, 296, 301, 337, 339 Humoral, 12, 17, 291, 293 Humour, 293 Hybridomas, 293, 298 Hydrocephalus, 293, 299 Hydrogen, 191, 198, 257, 266, 270, 279, 286, 294, 301, 306, 313, 315, 321 Hydrogen Peroxide, 294, 301 Hydrolysis, 182, 199, 264, 294, 314, 316, 318, 321

Hydroxamic Acids, 177, 294 Hydroxylysine, 274, 294 Hydroxyproline, 274, 294 Hypercapnia, 14, 294 Hypercholesterolemia, 122, 282, 294 Hyperglycemia, 41, 180, 211, 294 Hyperlipidaemia, 180, 294 Hyperlipidemia, 186, 208, 282, 294 Hyperlipoproteinemia, 294 Hyperplasia, 193, 294 Hypersensitivity, 260, 261, 279, 294, 301, 325 Hypertension, Pulmonary, 168, 294 Hypertriglyceridemia, 180, 282, 294 Hypertrophic cardiomyopathy, 193, 294 Hyperventilation, 14, 295 Hypocapnia, 14, 295 Hypoglycaemia, 278, 295 Hypoglycemia, 211, 295 Hypoglycemic, 211, 257, 289, 295, 334 Hypoglycemic Agents, 211, 295 Hypotension, 100, 167, 180, 197, 211, 254, 295 Hypothalamic, 174, 295 Hypothalamus, 265, 295, 317, 329 Hypothermia, 162, 163, 164, 295 Hypothyroidism, 114, 116, 186, 295 Hypoxanthine, 295, 339 Hypoxia, 14, 47, 204, 278, 295 I Id, 118, 128, 238, 239, 240, 244, 245, 250, 252, 295 Idiopathic, 23, 27, 28, 39, 42, 58, 61, 81, 104, 161, 295 Immune response, 58, 170, 196, 263, 265, 291, 295, 296, 303, 331, 337, 338, 339 Immune system, 12, 34, 170, 196, 267, 282, 295, 296, 301, 303, 307, 337, 339 Immunity, 34, 295, 296, 298 Immunization, 295, 296, 319 Immunodeficiency, 168, 296 Immunofluorescence, 12, 22, 296 Immunogenic, 26, 296, 301, 322 Immunoglobulin, 262, 296, 307 Immunologic, 27, 57, 272, 295, 296 Immunology, 259, 296 Immunophilin, 269, 296 Immunosuppressant, 196, 296 Immunosuppressive, 170, 196, 269, 296 Immunotherapy, 267, 279, 296 Impairment, 58, 77, 84, 111, 173, 174, 204, 278, 282, 286, 296, 305

Index 349

Implantation, 46, 61, 106, 141, 145, 162, 188, 296 Impotence, 165, 285, 296 In situ, 34, 296 In vitro, 8, 9, 10, 12, 34, 38, 40, 49, 55, 64, 296 In vivo, 8, 12, 34, 38, 48, 49, 50, 55, 62, 64, 190, 296, 306, 334 Incision, 296, 298 Incompetence, 288, 296 Incontinence, 168, 294, 296 Indicative, 153, 161, 164, 212, 296, 314, 337 Induction, 16, 28, 33, 91, 92, 296, 298, 328 Infarction, 12, 15, 28, 31, 34, 35, 39, 41, 61, 68, 79, 83, 84, 88, 93, 122, 130, 141, 145, 165, 169, 175, 176, 180, 186, 193, 195, 197, 211, 272, 276, 281, 296, 305, 308, 324, 338 Infection Control, 208, 210, 297 Infiltration, 290, 297, 319 Inflammatory bowel disease, 177, 201, 297 Influenza, 57, 297 Infusion, 9, 95, 114, 116, 117, 124, 126, 297, 308 Ingestion, 290, 297, 305, 318, 333 Initiation, 107, 297, 335 Inlay, 297, 325 Innervation, 50, 268, 297, 304 Inositol, 199, 297, 305, 326 Inositol 1,4,5-Trisphosphate, 199, 297 Inotropic, 18, 24, 64, 162, 163, 213, 260, 297, 306 Insight, 10, 24, 111, 297 Insomnia, 297, 319 Insulator, 297, 307 Insulin-dependent diabetes mellitus, 297 Insulin-like, 74, 242, 298 Intensive Care, 43, 44, 191, 298 Intensive Care Units, 191, 298 Intercostal, 298, 325 Interleukin-1, 91, 92, 298 Interleukin-18, 91, 92, 298 Interleukin-2, 298 Interleukin-6, 105, 298 Intermittent, 81, 95, 287, 298, 302, 315 Interstitial, 43, 180, 200, 210, 286, 298, 309, 324 Intestinal, 271, 273, 284, 290, 298, 340 Intestine, 266, 268, 298, 300 Intoxication, 278, 298, 339

Intracellular, 7, 17, 33, 38, 50, 52, 54, 152, 182, 296, 297, 298, 305, 310, 318, 320, 323, 326, 328 Intravascular, 179, 292, 298 Intravenous, 18, 32, 92, 297, 298 Intrinsic, 23, 25, 27, 35, 47, 154, 155, 166, 172, 175, 178, 185, 259, 266, 298 Intubation, 271, 298 Inulin, 289, 298 Invasive, 13, 17, 29, 46, 140, 185, 202, 295, 298, 303 Invertebrates, 34, 290, 298 Involuntary, 266, 287, 299, 308, 323, 328 Ion Channels, 299, 310 Ions, 266, 269, 281, 283, 289, 294, 297, 299, 314, 326 Irritable Bowel Syndrome, 168, 299 Ischemia, 15, 28, 29, 34, 35, 53, 161, 190, 265, 268, 299, 308, 324 Ischemic stroke, 32, 197, 299 Isoenzyme, 198, 277, 293, 299 Isomerases, 199, 299 Isopropyl, 203, 299 Isosorbide, 33, 299 J Jejunoileal Bypass, 266, 299 Jejunum, 266, 299 Joint, 12, 178, 213, 264, 299, 312, 332 K Kallidin, 268, 299 Kb, 232, 299 Keratoconus, 178, 299 Ketone Bodies, 279, 299, 300 Ketosis, 279, 300 Kidney Disease, 4, 10, 148, 201, 210, 211, 215, 232, 300, 324 Kidney Failure, 171, 243, 284, 290, 300 Kidney Failure, Acute, 300 Kidney Failure, Chronic, 300 Kidney stone, 201, 210, 300, 309, 336 Kinetic, 10, 300, 314 L Labile, 274, 300 Laminin, 266, 286, 300 Large Intestine, 280, 298, 300, 323, 329 Larynx, 300, 335, 337 Laxative, 123, 259, 300, 329 Left ventricular assist device, 38, 51, 61, 145, 162, 300 Length of Stay, 11, 300 Leprosy, 287, 301 Leptin, 9, 301

350 Congestive Heart Failure

Lesion, 26, 276, 287, 301, 302 Lethal, 61, 265, 301 Lethargy, 254, 294, 295, 301 Leucocyte, 260, 301 Leukocytes, 267, 268, 272, 291, 301, 307, 336 Leukotrienes, 263, 301 Library Services, 250, 301 Life cycle, 258, 301 Life Expectancy, 12, 37, 301 Ligaments, 276, 301 Ligands, 31, 182, 186, 204, 301 Ligation, 25, 41, 301 Linkage, 27, 289, 301 Lipid, 25, 83, 153, 264, 269, 287, 297, 301, 307, 313, 335 Lipid A, 26, 301 Lipid Peroxidation, 153, 301, 313 Lipophilic, 101, 196, 301 Lipopolysaccharides, 301 Lipoprotein, 282, 301, 302 Lithium, 10, 210, 302 Lobe, 262, 272, 302, 313 Localization, 34, 302 Localized, 168, 200, 260, 268, 276, 279, 296, 300, 302, 317, 326, 337 Longitudinal study, 46, 302 Long-Term Care, 19, 302 Loop, 15, 55, 132, 133, 226, 302 Lovastatin, 302, 328 Low-density lipoprotein, 83, 101, 282, 301, 302 Lower Esophageal Sphincter, 288, 302 Lubricants, 302 Lubrication, 168, 302 Lumen, 202, 284, 302 Lupus, 302, 332 Lymph, 94, 265, 272, 273, 284, 293, 302, 303, 331 Lymph node, 94, 265, 272, 302, 303 Lymphatic, 284, 297, 302, 303, 305, 329, 330 Lymphatic system, 302, 303, 329, 330 Lymphocyte, 57, 90, 162, 263, 303, 304 Lymphocyte Count, 162, 303 Lymphoid, 262, 301, 303 Lysine, 294, 303, 319 Lytic, 303, 328 M Macrophage, 298, 303 Macula, 303 Macula Lutea, 303

Macular Degeneration, 178, 303 Magnetic Resonance Imaging, 43, 48, 143, 303 Magnetic Resonance Spectroscopy, 17, 303 Major Histocompatibility Complex, 291, 303 Malignant, 97, 303, 309 Malnutrition, 259, 265, 269, 303 Malondialdehyde, 101, 303 Mammary, 276, 303 Mania, 303 Manic, 197, 302, 303 Manifest, 41, 161, 303 Man-made, 51, 304 Matrix metalloproteinase, 16, 33, 37, 49, 177, 304 Meat, 304, 326 Meatus, 304, 337 Mechanical ventilation, 14, 304 Mechanoreceptors, 14, 291, 304 Medial, 61, 264, 304, 330 Median Nerve, 204, 271, 304 Mediate, 23, 31, 59, 304 Mediator, 43, 193, 273, 298, 304, 328 Medical Records, 4, 304 Medicament, 203, 304 MEDLINE, 233, 304 Medullary, 210, 304 Melanin, 304, 316, 336 Melanocytes, 304 Melanoma, 97, 304 Memory, 111, 161, 172, 262, 278, 304 Meninges, 272, 305 Menopause, 305, 318 Menstrual Cycle, 10, 305, 319, 320 Menstruation, 282, 305, 319 Mental Disorders, 149, 305, 319, 321 Mental Health, iv, 5, 149, 232, 234, 305, 319, 321 Mental Processes, 281, 305, 321 Mental Retardation, 197, 305 Mesenchymal, 31, 285, 305 Metabolic disorder, 279, 305 Metabolite, 17, 302, 305, 319 Metabotropic, 152, 305 Metalloendopeptidases, 283, 305 Metastasis, 178, 304, 305 Metastatic, 94, 97, 305, 327 Metastatic cancer, 94, 305 Methanol, 21, 305 Methionine, 305, 331

Index 351

Metoprolol, 70, 80, 107, 122, 305 MI, 12, 20, 30, 39, 41, 61, 88, 95, 154, 169, 179, 185, 189, 243, 256, 305 Microbe, 305, 334 Microbiology, 257, 265, 306 Microcirculation, 211, 306 Microdialysis, 49, 306 Microorganism, 274, 306, 339 Microscopy, 25, 49, 60, 266, 306 Microtubules, 306, 313 Migration, 194, 306 Milrinone, 92, 213, 306 Mineralization, 269, 306 Mitochondria, 37, 306, 308, 312, 331 Mitochondrial Swelling, 306, 309 Mitosis, 263, 306 Mitral Valve, 166, 202, 306 Mobility, 12, 94, 183, 306 Mobilization, 183, 306 Modeling, 56, 147, 306 Modification, 40, 59, 181, 289, 306, 322 Monitor, 23, 29, 94, 159, 161, 172, 200, 243, 244, 272, 277, 307, 311 Monoclonal, 26, 104, 293, 307 Monoclonal antibodies, 26, 307 Monocytes, 91, 287, 298, 301, 307 Mononuclear, 307, 336 Monophosphate, 165, 168, 307 Mood Disorders, 54, 307 Motility, 168, 289, 307, 328 Movement Disorders, 307 Mucosa, 273, 284, 302, 307, 340 Mucus, 307, 336 Multicenter study, 13, 307 Multiple sclerosis, 177, 307 Multivariate Analysis, 4, 307 Muscle Contraction, 43, 182, 307, 326 Muscle Fibers, 265, 307, 308, 335 Muscle Proteins, 276, 307 Muscle Relaxation, 182, 307 Muscular Dystrophies, 282, 307 Myalgia, 297, 308 Myasthenia, 204, 308 Mydriatic, 280, 308 Myelin, 278, 307, 308 Myocardial Contraction, 35, 308 Myocardial Ischemia, 37, 172, 190, 261, 308 Myocardial Reperfusion, 308, 324 Myocardial Reperfusion Injury, 308, 324 Myocarditis, 86, 127, 308

Myocardium, 15, 16, 17, 26, 29, 31, 35, 41, 47, 53, 59, 65, 261, 305, 306, 308, 325, 338 Myofibrils, 269, 308 Myopathy, 136, 193, 308 Myopia, 178, 308, 309, 324 Myosin, 9, 56, 59, 136, 181, 182, 269, 307, 308, 335 N Narcosis, 293, 308 Nasal Mucosa, 297, 309 Natriuresis, 171, 194, 262, 309 Nausea, 281, 288, 300, 309, 319, 336 NCI, 1, 148, 231, 273, 309 Nearsightedness, 308, 309 Necrosis, 29, 91, 263, 268, 272, 276, 296, 305, 308, 309, 324 Neonatal, 12, 29, 127, 210, 309 Neoplasm, 309, 336 Nephritis, 210, 309 Nephrogenic, 10, 309 Nephrolithiasis, 210, 309 Nephrologist, 4, 309 Nephrology, 3, 74, 114, 116, 217, 309 Nephron, 16, 176, 290, 309 Nephropathy, 180, 193, 210, 211, 300, 309 Nephrosis, 309 Nephrotic, 10, 168, 208, 309 Nephrotic Syndrome, 10, 208, 309 Nervous System, 9, 175, 177, 182, 194, 204, 257, 258, 265, 269, 272, 273, 288, 291, 294, 301, 304, 307, 309, 310, 315, 328, 332 Neural, 43, 258, 293, 304, 309 Neurodegenerative Diseases, 197, 266, 309 Neurogenic, 310, 337 Neurologic, 204, 208, 209, 294, 310 Neuromuscular, 257, 310 Neuromuscular Junction, 257, 310 Neuronal, 308, 310, 315 Neurons, 83, 279, 286, 288, 310, 332 Neuropathy, 175, 180, 204, 211, 310 Neuropeptides, 182, 269, 310 Neurophysiology, 279, 310 Neurotransmitters, 199, 307, 310 Neutralization, 155, 310 Nitrates, 33, 169, 227, 310 Nitric acid, 310 Nitric Oxide, 17, 33, 34, 79, 91, 98, 167, 168, 211, 310 Nitrogen, 49, 203, 259, 286, 300, 310, 335 Nitroglycerin, 33, 92, 133, 310 Nitroprusside, 34, 310 Nonverbal Communication, 311, 321

352 Congestive Heart Failure

Norepinephrine, 10, 47, 87, 194, 258, 311 Nuclear, 59, 67, 78, 266, 283, 285, 304, 309, 311 Nuclear Proteins, 59, 311 Nuclei, 262, 283, 289, 303, 306, 311, 321 Nucleic acid, 295, 310, 311, 322 Nucleoproteins, 311 Nucleus, 262, 263, 265, 266, 273, 277, 279, 283, 285, 307, 311, 321, 331 Nutritional Support, 126, 311 O Observational study, 24, 311 Octreotide, 91, 204, 311 Ocular, 178, 211, 311 Office Visits, 5, 311 Ointments, 281, 311 Olfaction, 272, 311 Oliguria, 300, 312 Opacity, 279, 312 Ophthalmologic, 282, 312 Opsin, 312, 325 Optic Disk, 276, 280, 303, 312 Oral Health, 207, 312 Organ Transplantation, 208, 209, 312 Organelles, 272, 278, 304, 307, 312 Orgasm, 169, 312 Orthostatic, 100, 311, 312 Osmolality, 10, 312 Osmoles, 312 Osmotic, 259, 299, 306, 312, 328 Osteoarthritis, 177, 312 Osteoporosis, 130, 183, 186, 187, 197, 201, 259, 312 Outpatient, 4, 18, 30, 100, 106, 312 Overactive bladder, 180, 312 Overexpress, 59, 312 Overweight, 77, 118, 186, 242, 312 Ovum, 276, 301, 312, 319, 339 Oxidation, 11, 26, 50, 169, 257, 263, 273, 277, 279, 301, 312, 313 Oxidative Phosphorylation, 38, 50, 313 Oxidative Stress, 23, 33, 37, 41, 64, 91, 213, 313 Oxygen Consumption, 42, 93, 169, 286, 313, 325 Oxypurinol, 142, 313 P Pacemaker, 28, 106, 155, 158, 159, 160, 179, 313 Paclitaxel, 124, 313 Palliative, 313, 333

Pancreas, 257, 267, 280, 292, 297, 313, 327, 329, 336 Pancreatic, 180, 271, 273, 288, 313 Pancreatic Juice, 288, 313 Paralysis, 259, 313, 330 Parasitic, 266, 313 Parathyroid, 152, 313, 333 Parathyroid Glands, 313 Parathyroid hormone, 152, 313 Parietal, 262, 313, 315, 318 Paroxysmal, 254, 261, 313 Partial remission, 313, 324 Particle, 304, 313, 314, 329, 335 Particle Accelerators, 304, 314 Patch, 35, 48, 276, 314 Pathogenesis, 26, 56, 58, 64, 96, 208, 210, 314 Pathologic, 10, 43, 59, 62, 64, 160, 189, 257, 263, 267, 276, 294, 314 Pathologic Processes, 263, 314 Pathologies, 41, 175, 314 Pathophysiology, 3, 13, 15, 16, 17, 22, 47, 52, 75, 82, 111, 191, 194, 208, 209, 211, 212, 213, 215, 314 Patient Compliance, 147, 314 Patient Education, 242, 248, 250, 256, 314 Peer Review, 75, 113, 314 Penicillin, 262, 314 Penis, 169, 314 Pepsin, 314, 327 Peptide Hydrolases, 283, 314 Peptide T, 40, 314 Percutaneous, 40, 188, 202, 314 Perfusion, 14, 18, 38, 55, 163, 288, 295, 314 Pericardial Effusion, 94, 314 Pericardium, 314, 332, 338 Periodontal disease, 178, 315 Perioperative, 211, 315 Peripheral Nerves, 204, 301, 315, 330 Peripheral Nervous System, 278, 310, 315, 329, 331 Peripheral Vascular Disease, 168, 193, 211, 315 Peritoneal, 4, 210, 264, 315 Peritoneal Cavity, 264, 315 Peritoneal Dialysis, 4, 210, 315 Peritoneum, 315 PH, 60, 88, 315 Pharmaceutical Preparations, 172, 285, 289, 315 Pharmaceutical Solutions, 281, 315 Pharmacodynamic, 15, 41, 64, 315

Index 353

Pharmacokinetic, 41, 145, 315 Pharmacologic, 39, 209, 261, 316, 334, 337 Pharmacotherapy, 79, 83, 90, 100, 101, 128, 316 Pharynx, 288, 297, 316, 337 Phenotype, 12, 23, 31, 59, 198, 266, 316 Phenyl, 156, 172, 190, 191, 198, 203, 316 Phenylalanine, 316, 336 Pheromone, 152, 316 Phosphates, 50, 316 Phosphodiesterase, 115, 117, 165, 167, 168, 169, 180, 198, 260, 306, 316 Phosphodiesterase Inhibitors, 167, 168, 169, 316 Phospholipases, 316, 328 Phospholipids, 287, 297, 301, 316 Phosphorus, 201, 269, 313, 316 Phosphorylase, 269, 316 Phosphorylated, 59, 274, 316 Phosphorylation, 12, 38, 59, 316 Physical Examination, 143, 164, 216, 316 Physiologic, 10, 29, 59, 155, 173, 200, 259, 267, 298, 305, 316, 320, 323, 328, 332 Physiology, 22, 33, 43, 48, 49, 53, 56, 116, 118, 267, 270, 283, 309, 310, 316 Pigment, 266, 304, 316 Pilot study, 74, 144, 317 Pituitary Gland, 194, 317 Placenta, 317, 319 Plants, 259, 266, 270, 273, 280, 289, 290, 298, 311, 317, 326, 335 Plaque, 12, 178, 262, 264, 317 Plasma cells, 262, 317 Plasma protein, 259, 284, 317, 328 Plasmid, 50, 317, 338 Plasmin, 317, 334, 337 Plasminogen, 317, 334, 337 Plasticity, 50, 317 Platelet Activation, 317, 328 Platelet Aggregation, 33, 80, 261, 310, 317, 334 Platelets, 269, 310, 317, 334 Platinum, 302, 317 Pleura, 318 Pleural, 200, 318 Pleural cavity, 318 Pleural Effusion, 200, 318 Poisoning, 269, 278, 288, 298, 309, 318 Polycystic, 10, 318 Polypeptide, 164, 197, 260, 274, 284, 317, 318, 319, 321, 329, 335, 340 Polysaccharide, 263, 318, 321

Posterior, 261, 264, 313, 318, 330 Postmenopausal, 201, 259, 312, 318 Postnatal, 52, 318, 330 Postsynaptic, 318, 328, 332 Postural, 211, 318 Potassium, 43, 120, 201, 226, 239, 259, 318 Potentiate, 33, 318 Potentiating, 181, 318 Potentiation, 14, 318, 328 Power Sources, 157, 318 Practicability, 318, 335 Practice Guidelines, 80, 234, 244, 318 Pravastatin, 33, 319 Prazosin, 169, 212, 213, 227, 319 Preclinical, 8, 32, 319 Precursor, 177, 193, 262, 263, 264, 282, 284, 311, 316, 317, 319, 335, 336 Pregnancy in Diabetics, 279, 319 Preload, 64, 319 Premarin, 183, 319 Premenstrual, 201, 319 Premenstrual Syndrome, 201, 319 Primary endpoint, 57, 319 Primary Prevention, 46, 319 Probe, 38, 163, 306, 319 Procaine, 259, 319 Procollagen, 62, 319 Progesterone, 183, 319, 330 Progression, 12, 16, 17, 26, 29, 36, 40, 47, 49, 56, 68, 114, 116, 172, 173, 177, 203, 262, 320 Projection, 311, 320 Proline, 274, 294, 319, 320 Promoter, 50, 320 Prone, 188, 320 Prophylaxis, 58, 320, 337 Proportional, 312, 320 Propulsive, 173, 320 Prospective Payment System, 11, 320 Prospective study, 84, 302, 320 Prostaglandin, 262, 320, 334 Prostate, 267, 320, 336 Protease, 110, 274, 320, 334 Protein C, 10, 35, 152, 183, 197, 259, 260, 265, 301, 307, 320, 321, 335, 336 Protein Conformation, 260, 321 Protein S, 52, 58, 152, 214, 267, 321, 333 Proteins, 28, 29, 34, 49, 50, 51, 52, 55, 56, 58, 61, 152, 164, 182, 184, 198, 260, 263, 264, 267, 269, 271, 272, 273, 274, 276, 277, 286, 298, 304, 306, 307, 308, 310, 311, 314, 317, 321, 323, 328, 333, 335, 338

354 Congestive Heart Failure

Proteinuria, 76, 178, 193, 210, 290, 309, 321 Proteoglycans, 266, 286, 321 Proteolytic, 34, 58, 204, 260, 274, 317, 321, 334, 337 Protocol, 23, 24, 39, 53, 54, 110, 127, 321 Protons, 294, 303, 314, 321, 322 Proto-Oncogene Proteins, 313, 321 Proto-Oncogene Proteins c-mos, 313, 321 Proximal, 15, 34, 40, 168, 281, 299, 321, 327 Psychiatric, 54, 208, 209, 267, 305, 321 Psychiatry, 19, 44, 54, 85, 321, 338 Psychogenic, 321, 337 Psychology, 19, 29, 76, 281, 321 Psychomotor, 278, 321 Psychotherapy, 29, 321 Public Health, 20, 169, 185, 211, 215, 218, 234, 321 Public Policy, 233, 321 Publishing, 65, 212, 322 Pulmonary, 24, 39, 44, 52, 81, 102, 105, 107, 125, 140, 142, 159, 161, 164, 170, 184, 185, 188, 191, 193, 195, 200, 208, 209, 215, 260, 267, 273, 276, 286, 288, 292, 294, 295, 300, 301, 322, 325, 338 Pulmonary Artery, 24, 140, 184, 267, 322, 338 Pulmonary Circulation, 294, 322 Pulmonary congestion, 159, 322 Pulmonary Edema, 52, 107, 142, 159, 164, 200, 215, 273, 300, 322 Pulmonary hypertension, 39, 191, 193, 322 Pulmonary Ventilation, 295, 322, 325 Pulse, 13, 106, 155, 160, 172, 175, 179, 307, 322 Pupil, 276, 280, 308, 322 Purgative, 300, 322 Purines, 322, 327, 339 R Race, 103, 193, 209, 242, 243, 306, 322 Radiation, 261, 283, 284, 304, 322, 329, 339 Radioactive, 294, 296, 304, 307, 311, 322 Radioimmunoassay, 10, 322 Radiological, 314, 322 Radiopharmaceutical, 289, 322 Random Allocation, 322, 323 Randomization, 24, 51, 57, 323 Randomized clinical trial, 42, 46, 51, 323 Reabsorption, 10, 15, 171, 208, 323 Reactivation, 11, 323 Reactive Oxygen Species, 33, 34, 323 Reagent, 273, 323 Receptivity, 63, 323

Receptor, 8, 10, 28, 35, 40, 54, 56, 59, 80, 89, 103, 115, 117, 143, 152, 171, 175, 176, 182, 183, 186, 194, 197, 204, 239, 257, 263, 275, 290, 305, 314, 322, 323, 328 Receptors, Serotonin, 323, 328 Recombinant, 26, 59, 197, 323, 338 Recombination, 289, 323 Rectum, 263, 268, 280, 287, 288, 296, 297, 300, 320, 323 Red blood cells, 223, 285, 292, 323 Reductase, 33, 180, 302, 319, 323, 328 Refer, 1, 274, 302, 303, 323, 327 Reflective, 159, 323 Reflex, 43, 68, 83, 153, 323 Reflux, 204, 288, 323 Refraction, 308, 324 Refractive Power, 308, 324 Refractory, 106, 114, 117, 124, 155, 324 Regeneration, 31, 141, 324 Regimen, 147, 282, 314, 316, 324 Regurgitation, 61, 166, 173, 174, 202, 223, 288, 292, 324 Rehabilitative, 11, 324 Reliability, 30, 324 Remission, 19, 44, 324 Renal Artery, 163, 324 Renal failure, 155, 156, 157, 168, 193, 278, 324 Renal Osteodystrophy, 210, 324 Renal pelvis, 300, 324 Renin, 16, 163, 192, 193, 203, 204, 208, 211, 262, 270, 324 Renin-Angiotensin System, 163, 192, 211, 262, 270, 324 Reperfusion, 28, 29, 34, 35, 39, 177, 308, 324 Reperfusion Injury, 28, 36, 177, 324 Research Support, 39, 325 Respiration, 14, 68, 100, 173, 263, 270, 287, 307, 325 Respirator, 304, 325, 338 Respiratory Muscles, 13, 325 Respiratory Physiology, 76, 325, 338 Respiratory System, 169, 259, 325 Restitution, 161, 325 Restoration, 31, 57, 163, 308, 323, 324, 325, 339 Resuscitation, 283, 325 Retina, 276, 280, 303, 308, 325, 326 Retinal, 165, 275, 280, 312, 325 Retinol, 325 Retinopathy, 178, 211, 280, 325

Index 355

Retrospective, 49, 63, 153, 154, 325 Rheumatic Heart Disease, 208, 209, 325 Rheumatism, 325 Rheumatoid, 12, 177, 325 Rheumatoid arthritis, 177, 325 Risk factor, 4, 12, 13, 21, 22, 29, 40, 46, 52, 62, 74, 211, 218, 242, 243, 284, 320, 325 Risk patient, 46, 326 Rod, 265, 273, 326 Rosiglitazone, 142, 326 S Saline, 114, 117, 124, 326 Salivary, 280, 326, 331 Salivary glands, 280, 326 Saphenous, 276, 326 Saphenous Vein, 276, 326 Saponin, 25, 326 Sarcolemma, 29, 308, 326 Sarcomere, 181, 326 Sarcoplasmic Reticulum, 7, 8, 25, 54, 56, 190, 326 Saturated fat, 244, 326 Schizoid, 326, 339 Schizophrenia, 197, 326, 339 Schizotypal Personality Disorder, 326, 339 Scleroderma, 39, 193, 326 Sclerosis, 193, 197, 204, 264, 307, 326 Screening, 9, 16, 143, 152, 223, 242, 274, 326, 336 Second Messenger Systems, 310, 326 Secondary tumor, 305, 327 Secretin, 152, 327 Secretion, 9, 180, 182, 258, 282, 285, 289, 293, 295, 297, 307, 311, 326, 327 Secular trends, 31, 327 Sediment, 327, 336 Segmental, 208, 290, 327 Segmentation, 327 Seizures, 278, 313, 327 Self Care, 257, 327 Sella, 317, 327 Semisynthetic, 270, 327 Senile, 312, 327 Sensor, 155, 158, 173, 175, 187, 327 Sepsis, 177, 191, 238, 327 Septal, 81, 93, 124, 166, 262, 327 Septic, 177, 190, 327 Septum, 166, 265, 327 Septum Pellucidum, 327 Sequence Homology, 314, 327 Sequencing, 327, 332 Serine, 283, 321, 327, 328, 334

Serine Endopeptidases, 283, 328 Serologic, 62, 328 Serotonin, 180, 279, 287, 316, 323, 328, 335 Serous, 284, 318, 328 Serum, 4, 10, 24, 32, 62, 76, 83, 105, 204, 259, 261, 274, 277, 300, 302, 322, 328, 336 Serum Albumin, 4, 32, 322, 328 Sexually Transmitted Diseases, 208, 209, 328 Shivering, 164, 328 Shock, 161, 177, 180, 190, 261, 328, 335 Side effect, 145, 162, 165, 167, 207, 225, 258, 260, 267, 328, 334 Signal Transduction, 12, 34, 52, 60, 199, 269, 297, 328 Signs and Symptoms, 3, 176, 209, 215, 239, 324, 328 Simvastatin, 33, 328 Skeleton, 257, 287, 299, 320, 328, 329 Skin Aging, 178, 329 Skull, 329, 333 Sleep apnea, 127, 187, 188, 204, 329 Small intestine, 266, 282, 293, 298, 299, 329 Smooth muscle, 165, 194, 261, 269, 275, 287, 306, 310, 324, 329, 331 Social Environment, 322, 329 Social Support, 19, 30, 54, 136, 329 Sodium, 15, 77, 96, 171, 176, 191, 208, 214, 259, 309, 323, 329 Soft tissue, 268, 328, 329 Solid tumor, 178, 187, 262, 329 Solvent, 285, 305, 312, 315, 329 Soma, 329 Somatic, 8, 54, 293, 306, 315, 329, 337 Somatostatin, 204, 311, 329 Sorbitol, 293, 329 Sound wave, 275, 323, 329, 336 Spastic, 299, 330 Specialist, 4, 215, 240, 245, 280, 330 Specificity, 259, 283, 330 Sperm, 273, 330 Sphenoid, 327, 330 Sphenoidal, 91, 330 Spinal cord, 268, 272, 273, 304, 305, 309, 310, 315, 323, 330, 332 Spinal Nerves, 315, 330 Spleen, 261, 303, 330 Splint, 157, 188, 330 Sporadic, 309, 330 Standard therapy, 140, 330 Statistically significant, 223, 330 Steel, 182, 273, 330

356 Congestive Heart Failure

Stem Cells, 31, 330 Sterile, 313, 330 Steroid, 171, 266, 270, 277, 328, 330 Stimulant, 281, 299, 331 Stimulus, 12, 14, 171, 276, 281, 282, 283, 286, 297, 299, 323, 331, 333 Stool, 296, 299, 300, 331 Strand, 202, 331 Stroke Volume, 64, 164, 173, 185, 270, 331 Strophanthins, 270, 331 Subacute, 296, 331 Subclavian, 195, 265, 331 Subclinical, 89, 296, 327, 331 Subcutaneous, 258, 282, 331 Submaxillary, 285, 331 Submitochondrial Particles, 37, 331 Subspecies, 330, 331 Substance P, 305, 327, 331 Substrate, 15, 33, 50, 167, 168, 182, 284, 299, 331 Sudden cardiac death, 46, 331 Sudden death, 175, 196, 203, 331 Sulfur, 191, 286, 305, 331 Superoxide, 33, 332 Supplementation, 17, 121, 123, 125, 126, 128, 332 Suppression, 24, 171, 332 Supraventricular, 193, 196, 332 Survival Rate, 40, 41, 140, 146, 170, 196, 332 Sympathetic Nervous System, 9, 185, 192, 193, 194, 262, 265, 332 Sympathomimetic, 180, 285, 311, 332 Symptomatic, 176, 279, 319, 332 Synapses, 310, 332 Synaptic, 328, 332 Synchrony, 99, 332 Synovial, 12, 332 Systemic disease, 32, 210, 332 Systemic lupus erythematosus, 12, 210, 332 Systole, 37, 166, 277, 332 Systolic blood pressure, 106, 161, 332 Systolic heart failure, 26, 181, 333 Systolic pressure, 243, 333 T Tachycardia, 60, 125, 153, 196, 281, 333 Tamponade, 219, 333 Telecommunications, 140, 333 Temporal, 16, 18, 23, 49, 60, 303, 304, 333 Teratogenic, 280, 333 Testosterone, 261, 323, 333

Tetany, 313, 333 Tetracycline, 28, 333 Therapeutics, 9, 63, 103, 126, 169, 193, 208, 228, 333 Thermal, 81, 124, 128, 281, 333 Thiamine, 93, 119, 333 Thigh, 287, 333 Thoracic, 29, 66, 68, 125, 268, 280, 304, 318, 333, 339 Thorax, 257, 333, 337 Threonine, 314, 321, 327, 333 Threshold, 14, 58, 69, 160, 173, 178, 242, 294, 333 Thrombin, 287, 317, 320, 333 Thrombomodulin, 320, 333 Thrombosis, 82, 211, 321, 331, 333 Thromboxanes, 263, 334 Thrombus, 276, 296, 299, 308, 317, 334 Thyroid, 59, 116, 118, 145, 186, 193, 208, 209, 295, 313, 334, 336 Thyroid Gland, 313, 334 Thyroid Hormones, 59, 186, 334, 336 Thyrotropin, 295, 334 Thyroxine, 259, 316, 334 Tidal Volume, 158, 173, 295, 334 Tin, 271, 317, 334 Tissue Plasminogen Activator, 32, 334 Tolazamide, 181, 334 Tolerance, 29, 33, 36, 257, 290, 334 Tonicity, 292, 334 Tooth Preparation, 257, 334 Topical, 75, 227, 285, 294, 334 Torsion, 61, 296, 334 Toxic, iv, 27, 169, 266, 270, 280, 284, 295, 305, 310, 334 Toxicity, 4, 104, 123, 161, 271, 281, 334 Toxicology, 8, 96, 234, 334 Toxins, 263, 296, 307, 335 Trace element, 287, 334, 335 Trachea, 268, 300, 316, 334, 335 Traction, 273, 335 Transcription Factors, 51, 335 Transduction, 50, 52, 328, 335 Transfection, 267, 335 Translational, 57, 63, 335 Transmitter, 257, 299, 304, 311, 332, 335 Trauma, 32, 266, 278, 285, 291, 294, 309, 335 Treatment Outcome, 30, 136, 335 Triage, 45, 101, 335 Triglyceride, 294, 335 Tropomyosin, 182, 307, 335

Index 357

Troponin, 153, 182, 307, 335 Troponin C, 182, 335 Truncal, 183, 335 Tryptophan, 274, 328, 335 Tuberculosis, 276, 302, 335 Tumor marker, 267, 336 Tumor Necrosis Factor, 29, 104, 242, 336 Tumour, 91, 336 Type 2 diabetes, 4, 22, 336 Tyrosine, 49, 336 U Ubiquitin, 58, 336 Ulcerative colitis, 177, 297, 336 Ultrafiltration, 199, 214, 292, 336 Ultrasound test, 143, 336 Unconscious, 261, 295, 336 Urea, 300, 336 Uremia, 208, 300, 324, 336 Ureters, 300, 324, 336, 337 Urethra, 314, 320, 336, 337 Uric, 108, 260, 322, 336 Urinalysis, 143, 336 Urinary, 10, 91, 95, 197, 210, 265, 277, 289, 294, 296, 312, 319, 334, 336, 337, 339 Urinary Plasminogen Activator, 334, 337 Urinary Retention, 197, 319, 337 Urinary tract, 210, 265, 337 Urinary tract infection, 210, 265, 337 Urinate, 337 Urogenital, 289, 337 Urticaria, 261, 337 Uterus, 168, 272, 276, 283, 305, 319, 333, 337 V Vaccination, 57, 337 Vaccine, 57, 321, 337 Vagal, 175, 337 Vagina, 168, 305, 333, 337 Vaginal, 168, 302, 337 Vagus Nerve, 175, 335, 337 Valves, 154, 173, 188, 325, 337, 338 Vascular, 12, 13, 22, 31, 33, 39, 47, 54, 61, 76, 105, 110, 125, 163, 165, 180, 185, 193, 194, 197, 204, 208, 209, 211, 260, 261, 276, 279, 284, 296, 297, 306, 310, 317, 334, 337 Vascular endothelial growth factor, 47, 61, 76, 110, 125, 337 Vascular Resistance, 105, 260, 337 Vasoactive, 39, 79, 167, 168, 193, 337 Vasoconstriction, 194, 204, 281, 285, 337 Vasodilatation, 92, 198, 299, 337

Vasodilation, 33, 81, 124, 168, 262, 337 Vasodilator, 92, 153, 260, 268, 306, 308, 310, 337 VE, 140, 147, 338 Vector, 335, 338 Vein, 22, 125, 188, 261, 264, 265, 298, 311, 326, 331, 338 Venous, 43, 159, 169, 171, 176, 185, 188, 200, 264, 265, 267, 268, 272, 278, 310, 321, 338 Venous blood, 188, 267, 268, 272, 338 Venous Pressure, 176, 188, 338 Ventilation, 158, 338 Ventilator, 304, 325, 338 Ventricular Dysfunction, 17, 45, 46, 53, 74, 78, 193, 282, 338 Ventricular Function, 18, 45, 48, 53, 67, 89, 196, 338 Ventricular Pressure, 64, 338 Ventricular Remodeling, 35, 106, 127, 338 Venules, 267, 269, 284, 306, 338 Verapamil, 80, 338 Veterinary Medicine, 233, 338 Viral, 8, 127, 170, 190, 195, 196, 197, 276, 297, 335, 338 Viral vector, 8, 190, 338 Virulence, 334, 338 Virus, 58, 265, 284, 289, 290, 317, 335, 338, 339 Viscera, 329, 339 Visceral, 265, 315, 337, 339 Visceral Afferents, 265, 337, 339 Viscosity, 171, 339 Vitamin A, 297, 325, 339 Vitreous Hemorrhage, 280, 339 Vitro, 9, 34, 38, 55, 339 Vivo, 38, 47, 48, 49, 51, 55, 57, 174, 190, 339 W Wakefulness, 13, 278, 339 Weight Gain, 9, 339 White blood cell, 257, 262, 301, 303, 307, 317, 339 Windpipe, 316, 334, 339 Withdrawal, 106, 278, 339 Womb, 337, 339 Wound Healing, 178, 183, 197, 304, 339 X Xanthine, 64, 260, 313, 339 Xanthine Oxidase, 64, 260, 313, 339 Xenograft, 262, 339 X-ray, 143, 164, 255, 304, 311, 339

358 Congestive Heart Failure

Y Yeasts, 316, 339 Yolk Sac, 287, 339

Z Zymogen, 320, 340

Index 359

360 Congestive Heart Failure

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

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

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

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