HYPOTENSION A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R EFERENCES
J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS
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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright ©2004 by ICON Group International, Inc. Copyright ©2004 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1
Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Hypotension: 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: 0-597-84458-5 1. Hypotension-Popular works. I. Title.
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Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors, or authors. ICON Group International, Inc., the editors, and the authors are not responsible for the content of any Web pages or publications referenced in this publication.
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Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on hypotension. 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 HYPOTENSION .......................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Hypotension .................................................................................. 4 E-Journals: PubMed Central ....................................................................................................... 64 The National Library of Medicine: PubMed ................................................................................ 66 CHAPTER 2. NUTRITION AND HYPOTENSION ................................................................................ 99 Overview...................................................................................................................................... 99 Finding Nutrition Studies on Hypotension................................................................................. 99 Federal Resources on Nutrition ................................................................................................. 102 Additional Web Resources ......................................................................................................... 102 CHAPTER 3. DISSERTATIONS ON HYPOTENSION .......................................................................... 105 Overview.................................................................................................................................... 105 Dissertations on Hypotension.................................................................................................... 105 Keeping Current ........................................................................................................................ 106 CHAPTER 4. CLINICAL TRIALS AND HYPOTENSION ..................................................................... 107 Overview.................................................................................................................................... 107 Recent Trials on Hypotension.................................................................................................... 107 Keeping Current on Clinical Trials ........................................................................................... 109 CHAPTER 5. PATENTS ON HYPOTENSION ..................................................................................... 111 Overview.................................................................................................................................... 111 Patents on Hypotension ............................................................................................................. 111 Patent Applications on Hypotension ......................................................................................... 125 Keeping Current ........................................................................................................................ 145 CHAPTER 6. BOOKS ON HYPOTENSION......................................................................................... 147 Overview.................................................................................................................................... 147 Book Summaries: Federal Agencies............................................................................................ 147 Book Summaries: Online Booksellers......................................................................................... 148 Chapters on Hypotension........................................................................................................... 149 CHAPTER 7. MULTIMEDIA ON HYPOTENSION .............................................................................. 161 Overview.................................................................................................................................... 161 Video Recordings ....................................................................................................................... 161 CHAPTER 8. PERIODICALS AND NEWS ON HYPOTENSION ........................................................... 163 Overview.................................................................................................................................... 163 News Services and Press Releases.............................................................................................. 163 Newsletter Articles .................................................................................................................... 165 Academic Periodicals covering Hypotension ............................................................................. 167 CHAPTER 9. RESEARCHING MEDICATIONS .................................................................................. 169 Overview.................................................................................................................................... 169 U.S. Pharmacopeia..................................................................................................................... 169 Commercial Databases ............................................................................................................... 170 Researching Orphan Drugs ....................................................................................................... 170 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 175 Overview.................................................................................................................................... 175 NIH Guidelines.......................................................................................................................... 175 NIH Databases........................................................................................................................... 177 Other Commercial Databases..................................................................................................... 179 The Genome Project and Hypotension....................................................................................... 179 APPENDIX B. PATIENT RESOURCES ............................................................................................... 183 Overview.................................................................................................................................... 183
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Patient Guideline Sources.......................................................................................................... 183 Finding Associations.................................................................................................................. 204 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 207 Overview.................................................................................................................................... 207 Preparation................................................................................................................................. 207 Finding a Local Medical Library................................................................................................ 207 Medical Libraries in the U.S. and Canada ................................................................................. 207 ONLINE GLOSSARIES................................................................................................................ 213 Online Dictionary Directories ................................................................................................... 213 HYPOTENSION DICTIONARY................................................................................................. 215 INDEX .............................................................................................................................................. 323
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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 hypotension 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 hypotension, 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 hypotension, 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 hypotension. 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 hypotension, 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 hypotension. The Editors
1
From the NIH, National Cancer Institute (NCI): http://www.cancer.gov/cancerinfo/ten-things-to-know.
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CHAPTER 1. STUDIES ON HYPOTENSION Overview In this chapter, we will show you how to locate peer-reviewed references and studies on hypotension.
The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and hypotension, 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 “hypotension” (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: •
Heart in Uremia: Role of Hypertension, Hypotension, and Sleep Apnea Source: American Journal of Kidney Diseases. 38(4 Supplement 1): S38-S46. October 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. Summary: Cardiovascular disease is the leading cause of morbidity (illness) and mortality (death) in patients with end stage renal (kidney) disease (ESRD). The causes of this morbidity and mortality include those usually found in the general population, those related to the uremic status, and those related to dialysis treatment. This article focuses on the specific roles of hypertension (high blood pressure), hypotension (low blood pressure), anemia (low levels of hemoglobin, the oxygen carrying parts of the
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blood), hypoalbuminemia (low levels of protein in the blood), malnutrition, dyslipidemia (unhealthy levels of fats in the blood), reactive C protein, calciumphosphate product, dialysis modalities (hemodialysis versus peritoneal dialysis), and hyperhomocysteinemia. The authors put special emphasis on hyperparathyroidism as a traditional toxin. The emergent role of sleep apnea has been confirmed in animal models as well as in humans studied using polysomnography. There are difficulties in diagnosing coronary disease, because angiography has some risks, is expensive, and should be reserved for patients having symptoms of heart failure, patients with diabetes mellitus, or patients entering a transplantation list. This allows patients with coronary disease to undergo revascularization (adding blood vessels) through coronary artery bypass (preferably) or percutaneous transluminal angioplasty. Patients for whom surgery is not appropriate should be treated using more traditional medical procedures. 2 figures. 1 table. 36 references. •
Topsy-Turvy World of Postural Hypotension Source: Diabetes Forecast. 52(3): 76-79. March 1999. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: This article discusses the problem of postural hypotension. The symptoms of this condition, which is low blood pressure caused by standing up, include dizziness, light-headedness, blurred vision, weakness, and fatigue. People who have diabetes may experience postural hypotension as a complication of autonomic neuropathy. As autonomic neuropathy progresses, the autonomic nervous system loses its reactive ability, so people who have this complication can experience rapidly changing highs and lows in blood pressure that make their head swim. The article explains how the body normally maintains blood pressure when a person stands and how it reacts in those who have autonomic neuropathy. Although physicians can perform some tests that will help determine if a person has postural hypotension, this condition is not something that physicians recognize well. If a diagnosis of postural hypotension is made, the next step is to figure out what is causing it and how to treat it. Regardless of whether autonomic neuropathy or other factors are the cause of postural hypotension, much of the treatment focuses on relieving the symptoms and removing factors that may aggravate the condition. Drugs may also be used to the condition. The article also addresses the issue of treating postural hypotension in people who also have hypertension and stresses the need to tailor treatment for postural hypotension to a person's specific needs.
Federally Funded Research on Hypotension The U.S. Government supports a variety of research studies relating to hypotension. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.2 CRISP (Computerized Retrieval of Information on Scientific Projects) is a searchable database of federally funded biomedical research projects conducted at universities, hospitals, and other institutions.
2 Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).
Studies
5
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 hypotension. 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 hypotension. The following is typical of the type of information found when searching the CRISP database for hypotension: •
Project Title: ADRENAL INSUFFICIENCY AFTER MODERATE&SEVERE HEAD INJURY Principal Investigator & Institution: Cohan, Pejman E.; Harbor-Ucla Research & Educ Inst 1124 W Carson St Torrance, Ca 90502 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): Pituitary function is rarely considered in the care of patients with traumatic brain injury (TBI). Yet, TBI poses significant risk to pituitary function given the gland's encasement within the sella, its delicate infundibularhypothalamic structures and vulnerable vascular supply. Autopsy studies of fatal head injury victims confirm that up to one-third of patients sustain acute pituitary necrosis. The investigators and other investigators have documented chronic pituitary failure in long-term follow up studies of TBI subjects. The purpose of this study is to define acute post-traumatic changes in the hypothalamic-pituitary adrenocortical axis given that this hormonal axis is essential for survival, particularly in times of critical illness such as head injury. The major hypotheses to be tested in this study are: 1) a significant proportion of TBI victims suffer from unrecognized ASAI; 2) that ASAI results primarily from hypothalamic-pituitary hypoperfusion; 3) that the consequences of ASAI are systemic hypotension, increased vasopressor requirements and increased levels of serum and cerebrospinal fluid (CSF) proinflammatory cytokines; and 4) that treatment of individuals with ASAI with acute stress doses of glucocorticoids will improve blood pressure control, decrease CSF cytokine levels, shorten intensive care unit stay and improve neurological outcome. To test these hypotheses, they will first compare serial serum cortisol and ACTH levels over the first 10 days after injury in TBI versus matched non-TBI multiple trauma subjects to define ASAI. Next, TBI patients found to have inappropriately low cortisol levels that met criteria of ASAI, will be randomized to 48 hours of placebo or hydrocortisone therapy and changes in hemodynamics, cytokine levels, and neurological outcome will be measured. Pituitary/hypothalamic magnetic resonance imagings (MRIs) will be performed to assess for acute structural lesions and chronic pituitary volumetric changes. By diagnosing and treating acute traumatic neuroendocrine deficiency, this study may lead to dramatically improved management and neurological outcome of many future TBI patients. This proposal will help the candidate develop the theoretical and practical research skills necessary for an independent career in clinical investigation. The project will be done at two scientifically rich institutions supported by two GCRCs under the guidance of two experienced mentors from two different subspecialties appropriate for the study and the candidate's career development. Formal research instruction via the K30 Graduate Program at UCLA and courses at Harbor UCLA will complement the candidate's firm background in clinical medicine and endocrinology and enable him to successfully pursue a career as a clinical investigator in the field of neuroendocrinology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: AGE REGULATION
&
SYMPATHETIC
METABOLIC
CARDIOVASCULAR
Principal Investigator & Institution: Jones, Pamela P.; Integrative Physiology; University of Colorado at Boulder Boulder, Co 80309 Timing: Fiscal Year 2002; Project Start 01-JUN-1998; Project End 31-MAR-2003 Summary: The applicant, Pamela P. Jones, Ph.D., is a physiologist currently supported by an Individual National Research Service Award from NIA. Dr. Jones has demonstrated a consistent focus and record of research productivity in the area of autonomic nervous system (ANS) regulation of energy metabolism and cardiovascular function in humans. Her career goal is to develop an independent, extramurally-funded research program in this area as it pertains to gerontology and geriatric medicine. The KO1 Mentored Research Scientist Development Award would provide the opportunity to extend her current research skills to achieve this goal. Career Development/Training Plan. The training plan consists of 2 primary elements: 1) the acquisition of an impressive number of new research skills; and 2) structured activities including formal course- work in research ethics, biostatistics, and gerontology/geriatric medicine; participation in journal clubs and seminar series; regular mentoring interactions; and attendance/presentation at scientific meetings. A team of established senior investigators with expertise in all aspects of the proposed training plan has been formed to mentor Dr. Jones. Research Plan. The central theme of the research project is to determine the role of the ANS in the attenuated increase in energy expenditure (reduced thermic effect of food-TEF) and the fall in arterial blood pressure (postprandial hypotension) associated with feeding in older healthy sedentary humans. A secondary theme will be to determine if older adults who exercise regularly demonstrate a greater TEF and an absence of postprandial hypotension compared to sedentary older adults. Five specific aims have been developed to address these issues. The general hypothesis is that the lower TEF and postprandial hypotension observed in older sedentary adults will be related to an attenuated increase in sympathetic nervous system (SNS) activity. In contrast, physically active older adults will, in comparison, demonstrate a greater TEF, no postprandial hypotension, and an augmented SNS response. The expected results should provide new and clinically useful information concerning the influences of sedentary aging and habitual physical activity on an important component of body weight regulation (TEF) as well as cardiovascular disease risk (postprandial hypotension). Environment. The environment for Dr. Jones training is excellent. The sponsor, Douglas R. Seals, Ph.D., is an established investigator and mentor in aging research, and has a well-funded laboratory. He and the host department will provide Dr. Jones all of the necessary resources to successfully complete her training. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: AGE, HYPOTENSIO
EXERCISE,
THERMOGENESIS
AND
POSTPRANDIAL
Principal Investigator & Institution: Seals, Douglas R.; Professor; Integrative Physiology; University of Colorado at Boulder Boulder, Co 80309 Timing: Fiscal Year 2002; Project Start 01-FEB-2000; Project End 31-JAN-2005 Summary: In young adult humans, acute energy intake (feeding) evokes an integrative "postprandial" physiological response which includes an increase in metabolic rate (thermic effect of food intake--TEF) and a number of autonomic nervous system (ANS) and cardiovascular adjustments aimed at providing increased blood flow for digestion (splanchnic vasodilation) while maintaining arterial blood pressure (BP) at preprandial
Studies
7
levels. Some older adults with chronic diseases demonstrate a reduced TEF and/or a postprandial fall in BP ("postprandial hypotension"), but it is unknown whether this occurs with age in healthy adults. If the latter is true, some evidence suggests that these changes may not occur with age in adult humans who exercise regularly. The specific aims of the present proposal are to determine if: (1) TEF is lower and postprandial BP declines occur in middle-aged and/or older sedentary adults compared with young adult controls; (2) the lower TEF is due to attenuated postprandial increases in sympathetic nervous system (SNS) activity associated with reduced CNS sympathoexcitatory responsiveness to acute hyperinsulinemia; (3) the postprandial hypotension also is associated with: a) an attenuated or absent whole-limb and skeletal muscle vasoconstriction; b) a smaller reduction in cardiac vagal modulation of heart rate and an attenuated tachycardia; and c) a lower baseline cardiac vagal tone and arterial baroreflex sensitivity; (4) middle-aged and older adults who exercise regularly do not demonstrate the lower TEF and postprandial hypotension observed with age in sedentary humans, and whether this is associated with augmented SNS responses, CNS sympathetic responsiveness to circulating insulin, limb vasoconstriction, vagallymediated tachycardia, baseline cardiac vagal tone and baroreflex sensitivity; and (5) the reduced TEF and postprandial hypotension associated with sedentary aging are related to elevated adiposity. Because TEF contributes significantly to daily energy expenditure and, therefore, energy balance, the expected results should provide new and clinically important information concerning the effects of sedentary aging, regular exercise and adiposity on TEF in the context of age-related obesity and its metabolic and cardiovascular co-morbidities. Moreover, postprandial hypotension is associated with post-meal dizziness, weakness, syncope, cerebrovascular ischemia, and angina pectoris. As such, the expected results should provide new insight into the effects of sedentary aging, habitual exercise and body fatness on this clinically-important cardiovascular disorder. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ANTIFIBRILLATORY MECHANISMS OF INTRAPERICARDIAL AGENTS Principal Investigator & Institution: Verrier, Richard L.; Associate Professor; Beth Israel Deaconess Medical Center St 1005 Boston, Ma 02215 Timing: Fiscal Year 2002; Project Start 10-MAY-2001; Project End 31-MAR-2005 Summary: (the applicant's description verbatim): Intrapericardial drug administration has the intrinsic advantage of delivering high concentrations of compounds to intracardiac nerves, coronary vessels and myocardium while minimizing adverse side effects of systemic drug administration. Contact with these critical structures has the potential for novel antiarrhythmic actions. These include containment of profibrillatory effects of adrenergic nerves, coronary dilation without systemic hypotension, direct actions on the superficial sinus node without depressing contractility, and direct stabilization of electrical properties of the atria and ventricles. Available data indicate that intrapericardially administered agents have significant potential for suppressing arrhythmias, but the precise mechanisms involved have not been adequately defined. Another important limitation to development of intrapericardial antiarrhythmic therapy has been lack of access. We will employ our new technique which permits rapid (3-5 min), safe transvenous access to the normal pericardial space (Circulation 1998:98:2331). Specific Aims: 1. To test systematically the coronary hemodynamic and cardiac electrophysiologic effects of intrapericardial delivery of agents which act on critical epicardial sites including intracardiac nerves, coronary vessels, and epicardially dense
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transient outward current (Ito) channels in normal canines. 2. To determine the mechanisms whereby intrapericardially administered agents reduce cardiac vulnerability to arrhythmias during acute coronary artery occlusion and reperfusion. 3. To characterize the efficacy of intrapericardial agents in protecting against the profibrillatory effects of sympathetic nerve stimulation superimposed on acute myocardial ischemia and reperfusion. Cardiac vulnerability will be quantified by measuring epicardial and transmural dispersion of repolarization, by tracking T-wave alternans magnitude, a beat-to-beat variation in morphology of that waveform, and by monitoring spontaneous arrhythmias. Using the proposed methodologies and epicardial site-directed intrapericardial agents, important insights should emerge regarding antifibrillatory mechanisms of intrapericardial compounds. Ultimately, the proposed studies could lead to improved therapeutic approaches for suppression of lifethreatening arrhythmias. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ANTIHYPERTENSIVE MECHANISMS OF NEGATIVE ENERGY BALANCE Principal Investigator & Institution: Overton, J Michael.; Professor; Nutrition, Food & Exercise Sci; Florida State University 97 South Woodward Avenue Tallahassee, Fl 323064166 Timing: Fiscal Year 2002; Project Start 15-JAN-1998; Project End 31-DEC-2005 Summary: (provided by applicant): Obese individuals must enter negative caloric balance to reduce adiposity. Negative energy balance activates homeostatic mechanisms that appear to defend body weight. Thus, reduced caloric intake is associated with altered autonomic outflow producing concurrent reductions in energy expenditure, heart rate and blood pressure. The purpose of this proposal is to determine the mechanisms by which heart rate and blood pressure are decreased during reduced caloric intake. Substantial evidence supports the hypothesis that decreased circulating leptin signals reduced caloric availability and engages multiple hypothalamic pathways that stimulate appetite, reduce metabolic rate, and lower heart rate blood pressure. However, studies using animals with dysfunctional leptin signaling support the concept of leptin-independent regulation of cardiovascular function during negative energy balance. Therefore, the first aim of the proposal is to determine if leptin signaling is requisite for cardiovascular and thermogenic responses to reduced caloric intake. The approach will be to continuously determine oxygen consumption via indirect calorimetry and heart rate and blood pressure using telemetry, while infusing low levels of leptin peripherally during caloric restriction. Genetically altered mice have contributed significantly to understanding the potential mechanisms regulating energy balance. Thus, we will utilize both rat and mice models to accomplish the aims of this proposal. In the second aim, we propose to test the hypothesis that glucose sensitive neurons within the hypothalamus are requisite for normal regulation of energy expenditure and cardiovascular function during negative energy balance. In the third aim, we will test the hypothesis that inhibition of melanocortin receptors within the hypothalamus is requisite component of the cardiovascular effects of negative energy balance. Finally, we will examine the role of melanin concentrating hormone in the regulation of cardiovascular and metabolic responses to reduced caloric intake. Taken together, these studies will greatly enhance our understanding of the interrelationship between the regulation of energy balance and cardiovascular function and will have important implications for treatment of obesity and hypertension. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
Studies
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Project Title: ARTERIAL BAROREFLEX CONTROL OF BLOOD PRESSURE (EXERCISE) Principal Investigator & Institution: Raven, Peter B.; Professor and Chairman; Integrative Physiology; University of North Texas Hlth Sci Ctr Fort Worth, Tx 761072699 Timing: Fiscal Year 2003; Project Start 01-JUN-1996; Project End 30-JUN-2007 Summary: (provided by applicant): A number of investigations have demonstrated that arterial baroreflex (CBR) control of blood pressure has a primary role in providing the necessary regulation of the sympathetic neural outflow to active and inactive tissue beds associated with dynamic exercise. In addition, we have documented a reduced vasoconstrictive response to hypotension of the highly trained endurance athlete despite an augmented CBR mediated increase in MSNA. A growing body of evidence suggests that the regulatory role of sympathetic neural outflow to the vasculature is modulated by metabolic by-products released within the active tissue and involve mechanisms of functional sympatholysis. A suggested mechanism of functional sympatholysis is that contraction induced metabolites within the active muscle open ATP-sensitive potassium (KATP) channels and thereby partially inhibit sympathetic vasoconstriction. However, it has recently been demonstrated that the CBR mediated vasoconstriction within the active muscle provides the greatest reflex vasoconstrictor response to hypotension during exercise. Therefore, we hypothesize that the CBR has a fundamental role in the control of MSNA and skeletal muscle vasculature at rest and during exercise. Furthermore, we contend that the CBR regulation of vasomotor function in exercising muscle is altered by local metabolic by-products and their interaction with other vasoactive substances and the KATP channels of the vascular smooth muscle within the active tissue. In addition, these mechanisms of CBR control of the vasculature are modulated by endurance exercise training. To address these hypotheses: Comparisons of carotid baroreflex function curves of blood pressure (BP), MSNA and leg vascular conductance (LVC) will be made between rest, the nonexercising leg (NEL) and the exercising leg (EL) using the classic one-legged exercise protocol performed by humans. Carotid baroreflex function will be assessed using our well established modeling technique. Comparisons of CBR function curves of BP, MSNA and LVC will be made at rest, in the NEL and the EL (except MSNA) between average fit, high fit endurance trained athletes and NIDDM patients treated with glibenclamide and NIDDM patients treated with Metformin. We anticipate that the findings obtained from this project will provide a comprehensive understanding of the fundamental mechanisms involved in the regulation of arterial blood pressure by the arterial baroreflex and its influence on the regulation of vasomotion in active muscle tissue and inactive muscular tissue in matching blood flow to oxygen demand during exercise in humans. These findings will have implications for the care of patients suffering from non-insulin dependent diabetes mellitus (NIDDM), hypertension and cardiac failure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: AT2 RECEPTORS IN BLOOD PRESSURE AND RENAL FUNCTION Principal Investigator & Institution: Carey, Robert M.; Professor and Dean; General Clinical Research Ctr; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904 Timing: Fiscal Year 2002; Project Start 27-AUG-2001; Project End 31-JUL-2005 Summary: (provided by applicant): The overall objective is to test the hypothesis that the angiotensin type-2 (AT2) receptor plays an important role in the control of blood
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pressure and kidney function through the generation of bradykinin (BK), nitric oxide (NO) and guanosine cyclic 3', 5' monophosphate (cGMP). The specific aims are (1) to test the hypothesis that AT2 receptor stimulation mediates renal and systemic vasodilation and hypotension by increasing the production of BK, NO and cGMP and (2) to test the hypothesis that AT2 receptor stimulation, through increased renal production of BK, NO and cGMP, induces natriuresis. The investigators have demonstrated that the AT2 receptor is expressed in the kidney, heart and peripheral vasculature and stimulates renal BK, NO and cGMP. The principal investigator's recent studies in mice lacking the AT2 receptor (AT2-Null) demonstrate a sustained pressor and antinatriuretic hypersensitivity to angiotensin II (ANG II), accompanied by a marked reduction in BK, NO, cGMP. These results suggest that the AT2 receptor may function as an opponent of the actions of ANG II at the AT1 receptor. The principal investigator has recently demonstrated that valsartan-infused rats without functioning AT1 receptors have hypotensive respoflses to Ang II that are fully blocked by the AT2 receptor antagonist, PD 123319.The proposed experiments represent a systematic approach to the role of the AT2 receptor in vasodilation and natriuresis and the renal mechanisms of these actions in the valsartan-infused (AT1 receptor-blocked) rat model. This model will allow evaluations of the role of the AT2 receptor and its signalling mechanisms in the absence of interference by functional AT1 receptors. The proposed studies will clarify the role of the AT2 receptor in the control of blood pressure and kidney function. An understanding of the function of the AT2 receptor is necessary for an assessment of its potential role in the pathophysiology of hypertension and as a target for antihypertensive therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BAROREFLEX FAILURE: MECHANISMS AND THERAPY Principal Investigator & Institution: Robertson, Rose M.; Professor of Medicine; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2007 Summary: (provided by applicant): This proposal investigates the mechanism underlying the clinical manifestations of baroreflex failure and of baroreflex dysfunction. The Vanderbilt Autonomic Dysfunction Center provides a unique resource of patient referrals with baroreflex failure. This includes patients with the familial paraganglioma syndrome; which leads to predictable bilateral carotid sinus deafferentation. In addition, the sporadic unilateral form of this disorder will allow us to assess the laterality of effects. We will test the hypothesis that the pathologic decrease in vagal afferent activity in these patients alters the activity of multiple cortical and subcortical areas, by comparing in normal volunteers and in patients using electrical cervical vagal stimulation for the treatment of seizures the hemodynamic responses to discrete cortical stimuli (visual, auditory, taste and nociceptive stimuli, Stroop testing and mental arithmetic), the response of vasopressin, and autonomic activation with spectral analysis of blood pressure and heart rate and plasma catecholamines as well as defining the functional level of specific brain receptor fields. We will define mechanisms supporting orthostatic blood pressure in these patients, specifically by testing the effect of vestibular input with differential tilt studies. In a separate series of studies of baroreflex dysfunction, we will test the hypothesis that variable levels and durations of acute and chronic glycemic control alter baroreflex function in diabetics, utilizing direct assessment of baroreflex function, and blood and plasma volume determination during insulin clamp studies. We will also define the effect of carotid endarterectomy or stenting on baroreflex function and utilize carotid ultrasound to evaluate the role of the
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mechanical/vascular component. We will further assess the hypothesis that therapeutic options of demonstrated utility either in pilot studies of baroreflex failure and/or in patients with other forms of automomic dysfunction (e.g., clonidine, oral water, citrulline, and modulation of prostaglandin synthesis) are effective in patients with baroreflex dysfunction or failure. The data derived from these studies will provide important information that should lead to improve treatment for these patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BIOMECHANICS OF BRAIN EDEMA AND INTRACRANIAL PRESSURE Principal Investigator & Institution: Marmarou, Anthony; Professor and Vice-Chairman; Division of Neurosurgery; Virginia Commonwealth University Richmond, Va 232980568 Timing: Fiscal Year 2002; Project Start 01-DEC-1984; Project End 31-AUG-2006 Summary: The contribution of brain edema to raised intracranial pressure (ICP) in cases of traumatic injury remains a critical problem for which there is no effective clinical treatment at present. Elevations in intracranial pressure are a frequent cause of death, and result in a very poor prognosis in survivors. The long-term goal of this research is to elucidate those factors responsible for the development of traumatic brain edema. In the previous five years this laboratory has completely altered the thinking regarding the pathophysiology of this problem. We have introduced the new concept of a predominantly cellular edema after traumatic brain injury, as evidenced by a reduction of the Apparent Diffusion Coefficient (ADC) of water in magnetic resonance studies. This is in sharp contrast to the generally held view that edema is of vasogenic origin, secondary to blood brain barrier breakdown, extravasion of intravascular protein and osmotic movement of water into the brain Having identified the importance of cellular edema in TBI, this application will focus on the mechanisms responsible for traumatic cellular edema. We believe that this cellular edema is caused by disruption of ionic homeostasis and membrane pumps secondary to energetic crisis, which eventually leads to movement of sodium and obligatory water into brain. Moreover, we believe that this energy crisis, which occurs in the presence of adequate CBF, is associated with mitochondrial impairment as evidenced by reductions in N-acetyl- aspartate (NAA). Our four specific aims include utilizing newly developed flexible ion-selective K+ and Na+ electrodes to provide an accurate assessment of ionic shifts in diffuse and focal injury and how they are altered with hypoxia and hypotension. We will also measure the amount of tissue sodium and potassium associated with increases in brain tissue water and determine whether the net cation shift can account for all of the observed cellular edema. This will provide a basis for understanding the development of cellular edema and will reaffirm its major role of in the swelling process. Using each animal as its own control we will utilize non-invasive Magnetic Resonance Proton Spectroscopy (MRS) to rapidly assess the onset and degree of mitochondrial impairment in regions of cell swelling as reflected by changes in ADC, NAA and ATP as the injury evolves. We will confirm these measures at sacrifice with high performance liquid chromatography (HPLC). This information taken in concert with cation shifts will confirm our contention that ionic dysfunction and cellular edema occur as a result of mitochondrial impairment, and provide fresh avenues for therapeutic intervention. Finally, on the basis of this new understanding, we will evaluate the effectiveness of Cyclosporin A, a compound with known mitochondrial protective properties, in blunting the reduction of NAA and ATP, tissue cation changes and brain edema which occur with TBI. We will also evaluate the
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differential effect of FK- 506, a similar compound to CsA but with only calcineurin activity, to help dissect the mechanisms of mitochondrial protection Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BIONIC BAROREFLEX SYSTEM FOR BLOOD PRESSURE CONTROL Principal Investigator & Institution: Diedrich, Andre; Transtk, Inc. 1256 Briarcliff Rd Atlanta, Ga 303062636 Timing: Fiscal Year 2002; Project Start 15-AUG-2002; Project End 31-JAN-2004 Summary: (provided by applicant): Patients with multiple system atrophy (MSA), a sporadic and progressive neurodegenerative disorder, suffer from orthostatic hypotension, postprandial hypotension and supine hypertension. Hypotension causes presyncopal symptoms usually within seconds of standing and requires the patient to sit or lie down to prevent syncope. Supine hypertension reduces sleep quality through excessive nocturnal diuresis, and results in blood volume loss during the night, which aggravates orthostatic hypotension during the day. New strategies of treatments are required which take into account this cycling between hypertension and hypotension. Recent studies in our laboratory have yielded the unexpected observation that sympathetic activity is present in MSA, but is not subject to normal control mechanisms. This sympathetic activity produces inappropriate supine hypertension, but is not able to prevent the profound orthostatic hypotension. The identification of residual sympathetic activity in MSA has important implications for new therapeutic approaches. We hypothesize that a bionic baroreflex system based on electrical epidural spinal stimulation will help to replace the missing control of sympathetic activity by the vasomotor center. Preliminary data in animals showed that such a system maintained blood pressure during orthostatic stress. The purpose of this grant proposal is to search for an effective and practical bionic baroreflex system for patients with MSA and baroreflex failure. First, we will develop a prototype bionic baroreflex control system using baroreflex-denervated rats. Then, the system will be applied to control artificially, the muscle sympathetic nerve activity in patients who already have an epidural electrical stimulator in place for the control of chronic pain. A Phase II study would involve studies in animals and in patients with MSA to determine the long-term efficacy of the bionic baroreflex system in improving blood pressure control. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: BNOS-NO ON NEONATAL ARTERIAL PRESURE REGULATION IN NTS Principal Investigator & Institution: Ma, Sheng-Xing X.; Harbor-Ucla Research & Educ Inst 1124 W Carson St Torrance, Ca 90502 Timing: Fiscal Year 2002; Project Start 01-AUG-2001; Project End 31-JUL-2004 Summary: (provided by applicant): Despite the dramatic rise in circulating norepinephrine (NE) concentrations during transition from fetal to newborn life, arterial blood pressure does not substantively change. However, altered regulation of arterial blood pressure at birth, perhaps due to prematurity or depleted NE following fetal stress, may result in neonatal hypotension or hypertension. The nucleus tractus solitarius (NTS) is the principal sensory nucleus for central control of the circulation. Nitric oxide (NO) in the NTS plays an important role in the central inhibition of sympathetic tone and thus decreases blood pressure. We have recently shown that ovine brain NO synthase (bNOS) expression in the NTS is markedly enhanced in neonates at 4 hours following birth, as compared to the term fetus. Consistent with the postulated role
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of NO, fetal arterial blood pressure is decreased by fourth ventricle administration of a NO donor and increased by a NO synthesis inhibitor. Furthermore, our preliminary results demonstrate that fourth ventricle administration of a NE uptake inhibitor increases ovine fetal bNOS protein and y-aminobutyric acid (GABA) expression in the NTS and rostral ventral medulla (RVM). We hypothesize that during fetal and neonatal life (1) elevated circulating NE induces up-regulation of bNOS in the NTS during birth transition, and (2) the bNOS-NO-GABA system regulates neonatal arterial blood pressure in the NTS-RVM central sympathetic pathways. In view of the critical importance of fetal/neonatal arterial blood pressure regulation, our major aims are: 1) If exogenous fetal NE mimics up-regulation of bNOS-NO in the NTS and the RVM? 2) If arterial blood pressure increases and NTS bNOS-GABA expression decreases in newborn lambs by fourth ventricle administration of nNOS antisense oligonucleotides before birth? and 3) If the enhanced bNOS and GABA expression in the NTS and RVM regions at birth are promoted by an inhibitor of NE uptake? These studies will examine bNOS expression in the NTS and RVM neurons in the ovine fetus and neonate. Quantification of arterial blood pressure, plasma NE concentrations, bNOS and GABA expressions in brain regions will be incorporated with neuropharmacological manipulations to test our hypotheses. These results will advance our understanding of the sites and mechanisms for bNOS-NO-GABA effects on arterial blood pressure regulation during the transition from fetal to newborn life and will yield new insights regarding noradrenergic mechanisms for bNOS regulation and central neurocardiovascular control at birth. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CARDIAC DEPRESSION IN GRAM-POSITIVE SEPSIS--ROLE OF TLR2 Principal Investigator & Institution: Vallejo, Jesus G.; Medicine; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 02-JUL-2001; Project End 30-JUN-2006 Summary: (provided by applicant): The systemic inflammatory response induced by gram-positive bacteria is associated with considerable morbidity and mortality attributable to refractory hypotension, cardiac dysfunction and multiorgan failure. Despite the potentially important role that TNF-a, lL-1b and NO may play in producing cardiac decompensation in human septic shock, little is known with regard to mechanism(s) by which bacterial pathogens induce their expression in the heart. A major advance in the understanding of the early events in gram-positive bacterial signaling has been the identification of Toll-like receptors (TLRs). Recent studies suggest that TLR2 may be a pattern recognition receptor that binds gram-positive bacteria and their cell wall components. In addition, TLR2 is an effective signaling molecule that activates NF-kB, leading to cytokine production. The long-term objectives of this research initiative are not only to delineate the molecular pathogenesis of gram-positive septic shock, but also to develop strategies to prevent or attenuate the untoward effects of sepsis in the heart. Toward this end, the immediate specific objective of this application will be to delineate the role of TLR2 in the pathogenesis of myocardial dysfunction associated with gram-positive septic shock. Two closely interrelated hypotheses will be tested: first, signaling via TLR-2 is responsible, at least in part, for the induction of proinflammatory mediators associated with myocardial inflammation following infection with the gram-positive bacterium Staphylococcus aureus; second, TLR2 is responsible, at least in part, for the development of or S. aureus-induced left ventricular contractile dysfunction. These hypotheses will be tested in three Specific
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Aims. Specific Aim 1 will determine whether TLR2 mediates the inflammatory response induced by gram-positive bacteria in the heart. Specific Aim 2 will determine whether TLR2 mediates the cardiac response following infection with S. aureus. Specific Aim 3 will determine whether immunotherapeutic interventions designed to interdict signaling via TLR2 prevent and/or modify left ventricular dysfunction in gram-positive septic shock. These studies will provide definitive new information with respect to the mechanisms responsible for the deleterious effects of gram-positive sepsis on cardiac function and structure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REACTIVITY
CARDIOPLEGIA
AND
CORONARY
MICORVASCULAR
Principal Investigator & Institution: Sellke, Frank W.; Professor and Chief; Beth Israel Deaconess Medical Center St 1005 Boston, Ma 02215 Timing: Fiscal Year 2002; Project Start 01-AUG-1992; Project End 31-JUL-2005 Summary: (provided by applicant): We propose to examine changes in coronary and peripheral microvascular reactivity and identify the respective mechanisms of change, which occurs as a consequence of extracorporeal circulation/cardiopulmonary bypass (CPB) and cardioplegia. This will be accomplished by a unique approach to the study of the coronary, mesenteric and skeletal muscle microcirculations using both in vivo and in vitro techniques, such that auto regulatory and metabolic influences are minimized or eliminated. Standard cellular and molecular approaches will be used to determine what specific changes occur in vasomotor pathways. Porcine models will be employed to define the effects of CPB and cardioplegia on vascular signal transduction, while isolated micro vessels from rats will be used to examine the effects of specific pathologic processes on vascular reactivity. Since CPB and cardioplegia inherently involve numerous simultaneous pathologic processes, whenever possible, the effects of specific pathologic processes will be inhibited and the consequent change in vascular function assessed. In vitro experiments on intact isolated micro vessels will also be performed to identify the changes in signal transduction responsible for altered tone operating through conventional and novel isoforms of protein kinase C (PKC), mitogen activated protein (MAP) kinases and myosin light chain (MLC) phosphorylation pathways in vascular smooth muscle. The following specific aims will be addressed: 1) to identify the mechanisms responsible for altered agonist-induced and myogenic microvascular contraction after cardioplegia in the porcine model. 2) To examine the mechanisms causing reduced microvascular smooth muscle myogenic and agonist induced contraction of peripheral (skeletal muscle and mesenteric) micro vessels after CPB. 3) To examine the effects of hydrogen peroxide and other enhancers of oxidative stress and inhibitors of oxidant stress on PKC-mediated contraction in isolated peripheral (skeletal and mesenteric) rat vessels. In addition, we will study the effects of prior exposure of vessels to alpha-1 adrenergic (phenylephrine), thromboxane A2 (U46619), and vasopressin. 4) The relationship of vasomotor regulation of peripheral micro vessels to direct cytokine exposure will be examined in vitro. Specifically, peripheral micro vessels will be exposure to platelet-derived growth factor, vascular endothelial growth factor, tumor necrosis factor-alpha interleukin-6, and interleukin-8 alone and in combination and in the presence of increased oxidative stress. These studies should provide a better understanding of the cause, potential prevention and treatment of systemic hypotension and mal-perfusion and may improve the outcome of patients (reduced morbidity and shorter length of hospitalization) undergoing cardiac surgery in which CPB support is utilized. Finally, given that alterations in vasomotor regulation and other
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pathological conditions such as increased vascular permeability often share common mechanisms, the findings of the experiments described in this proposal may have universal implications. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CARDIO-RENAL ACTIONS OF NOVEL NOCICEPTIN ANALOGUES Principal Investigator & Institution: Kapusta, Daniel R.; Associate Professor; Pharmacology; Louisiana State Univ Hsc New Orleans New Orleans, La 70112 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2007 Summary: (provided by applicant): Nociceptin/orphanin FQ (N/OFQ) is an endogenous opioid-like peptide that produces marked effects on cardiovascular (hypotension, bradycardia, sympathoinhibition) and renal excretory (water diuresis) function in animals. Using selective ligands for the N/OFQ peptide receptor (NOP), we have obtained evidence that there exist separate pathways in the brain and periphery by which N/OFQ affects cardiovascular and renal function. As proposed in this application, the development of new ligands (peptide and non-peptide) selective for the NOP receptor, a pertussis toxin-sensitive G-protein receptor, will provide the basic pharmacological tools necessary to systematically study these tissue/system specific pathways. The hypothesis to be tested is that there exist separate central and peripheral NOP receptor pathways that affect cardiovascular and renal function, and that selective activation of the peripheral NOP receptor pathway with novel peptide and non-peptide ligands can evoke a free-water diuresis devoid of adverse cardiovascular/CNS effects. The investigations proposed in this amended application will test this hypothesis using a multidisciplinary approach that can be successfully achieved by the collaborative efforts of two established investigators in the N/OFQ research field, these being the P.I., and Dr. Domenico Regoli. This will entail the synthesis of novel NOP receptor ligands using peptide and non-peptide chemistry, which will be used to elucidate the biological actions, tissue distribution and signal transduction pathways of N/OFQ and NOP receptor ligands in the brain, periphery and kidneys. These studies will employ molecular, cellular and classical pharmacological approaches involving isolated organs, tissues and whole animals; and in vivo analysis of the cardiovascular and renal responses produced by these novel NOP receptor ligands. The use of genetically modified transgenic NOP receptor knockout mice (whole animal/tissue) will provide an innovative approach to understand the effects of N/OFQ and NOP ligands at each site. The pharmacological evaluation of N/OFQ and NOP receptor ligands in different in vitro bioassays and cell culture will explore the pharmacology of the NOP receptor system and the underlying signaling pathways by which NOP receptor ligands elicit diverse cardiovascular and renal responses. Finally, the potential for novel peripherally acting NOP ligands to produce a therapeutic water diuresis in states of vasopressin excess will be explored. It is anticipated that work in this area will provide new strategies for the treatment of different pathological states associated with fluid retention and/or hyponatremia/hypokalemia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CARDIOTOXICITY OF STREPTOCOCCAL PYROGENIC EXOTOXINS Principal Investigator & Institution: Schlievert, Patrick M.; Professor; Microbiology; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2002; Project Start 01-JUL-1986; Project End 31-MAR-2007
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Summary: (provided by applicant): The long term goals of this project are two fold: a) to evaluate the role of pyrogenic toxin superantigens, notably streptococcal pyrogenic exotoxins (SPEs, scarlet fever toxins, in causing both acute toxic shock syndrome and vascular illnesses and chronic autoimmune and allergic diseases, and b) to analyze the structure:function relationships among the SPEs and between the SPEs and the staphylococcal enterotoxins and toxic shock syndrome toxin-1, with the intent of clarifying the molecular mechanisms of action of the toxins, developing toxoid vaccines, and developing useful adjuvants of the toxins. Specific aims of the present application include: a) Biochemical and immunobiological characterization of SPEs J and L, and determining the three dimensional structure of both toxins (complex structures of the SPEs with the variable part of the beta chain of the T cell receptor and major histocompatibility complex II molecules will be determined if such structures are likely to generate new data). Our role in this aim will be to characterize the new SPEs, provide toxins for structural studies, consult on the best conditions for use in crystallization, and preparation and testing mutant toxins for confirmation that important contact residues on the SPEs are required for activity; b) Characterization of SPE C's, and possibly SPE J's ability to cross mucosal surfaces. Studies will include establishment of vaginal epithelial monolayers and stratified epithelium in Transwells and evaluation of the mechanism by which the toxin(s) traverse the layers. We will also evaluate the ability of biologically inactive toxins to permeabilize the epithelium, both in vitro and in rabbits, to other agents, and thus, determine whether the toxoids may be useful as delivery agents (and possibly adjuvants) for transmucosal immunization; and c) Characterization of the mechanism of streptococcal toxic shock syndrome with necrotizing fasciitis in rabbits. We hypothesize that SPEs cause both hypotension and delayed phagocytosis through exaggerated cytokine release, which in turn allows continued growth of the invasive organism with production of necrotizing fasciitis through hemolysins and protease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CARDIOVASCULAR CAUSES OF FALLS/SYNCOPE IN THE ELDERLY Principal Investigator & Institution: Maurer, Mathew S.; Medicine; Columbia University Health Sciences New York, Ny 10032 Timing: Fiscal Year 2002; Project Start 01-JUL-2001; Project End 30-JUN-2006 Summary: Syncope and falls cause significant morbidity and mortality in the elderly. This proposal will explore the role of vascular stiffness in disorders of blood pressure [BP] regulation that result in falls/syncope in the elderly. The research will focus on orthostatic hypotension and carotid sinus hypersensitivity [CSH], which account for a significant percentage of falls/syncope in the elderly. With the aging of the population, the need to understand the pathophysiology of these disorders is evident. The initial stages of the applicant's professional career have demonstrated a strong commitment to understanding how age related changes in cardiovascular physiology result in falls/syncope in the most rapidly growing segment of the population. This Mentored Patient Oriented Research Career Development Award will permit the acquisition of new skills for measuring vascular stiffness and pursuit of didactic training in biostatistics and experimental clinical design facilitating the applicant's development as a clinical investigator. The overall hypothesis to be tested is that age-related changes in vascular function predispose the elderly to disorded BP regulation. Initially, the applicant will prospectively evaluate beat-to-beat orthostatic changes in BP and the incidence of falls in nursing home residents to determine if the timing and degree of postural changes in BP adds prognostic value, if changes in SBP and DBP are equivalent
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in predicting subsequent falls in order to determine what degree of decline in BP has the best predictive value. This study will improve our ability to identify elderly subjects at risk for falls and identify subjects for participation in future mechanistic studies. Subsequently, we propose to: (1) evaluate the role of venous stiffness in the development of symptomatic hypotension during prolonged orthostatis and after meal ingestion, (2) determine the impact of arterial stiffness on the decline in baroreflex control of heart rate with age to evaluate if there is a systematic bias in the measurement of baroreflex function when using peripheral as compared with central aortic pressure, (3) compare the degree of vascular stiffness, extent of athlerosclerosis and baroreflex control of heart rate in elderly patients with CSH and age and sex-matched controls. This research will take place in the Autonomic Function Laboratory in the Irving Center for Clinical Research, the Hebrew Home for the Aged and the Division of Circulatory Physiology of Columbia University. Coursework in biostatistics and experimental clinical design will be pursued in the Columbia University School of Public Health. These courses will compliment participation in the Mentoring Program in the Division of Circulatory Physiology that will include one-on-one meetings and courses on the design of clinical trials, good clinical practice and responsible conduct of research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CENTRAL CARDIOVASCULAR CONTROL DURING BLOOD LOSS Principal Investigator & Institution: Schadt, James C.; Associate Professor; Dalton Research Center; University of Missouri Columbia 310 Jesse Hall Columbia, Mo 65211 Timing: Fiscal Year 2002; Project Start 15-JUN-2001; Project End 31-MAY-2005 Summary: A thorough understanding of the physiological consequences of traumatic blood loss is essential to effective medical management of the problem and the associated complications. The response to blood loss in conscious animals (including humans) is biphasic. The pattern is characterized initially by sympathoexcitation and arterial blood pressure maintenance with little activation of humoral systems. This is followed later by sympathoinhibition, vasodilation, hypotension, and increased release of vasopressin, epinephrine and renin. Very little is actually known about the central nervous system networks controlling the onset of hypotension. The periaqueductal gray (PAG) is a brain area that may be important in the control of the cardiovascular and neurohumoral response to blood loss. Our general hypothesis is that the ventrolateral PAG is important in the central control of the integrated hemodynamic and neurohumoral response to hemorrhage and stressful sensory stimuli. We will use a combination of approaches to evaluate ventrolateral PAG involvement in cardiovascular control during acute hypotensive hemorrhage in conscious rabbits. The use of this combination of approaches is novel, and this will be one of the first studies to address ongoing central cardiovascular control mechanisms during a physiological event such as hemorrhage. The Specific Aims of this study are: 1) To define the role of the ventrolateral PAG in the hemodynamic response to blood loss and stress in the conscious rabbit. 2) To quantify the response of ventrolateral PAG neurons during hemorrhage and stress in the conscious rabbit. 3) To understand the role of serotonergic and opioidergic mechanisms in the ventrolateral PAG during blood loss in the conscious rabbit. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CENTRAL NERVOUS SYSTEM DYSFUNCTION IN SHOCK AND TRAUMA Principal Investigator & Institution: Mcintosh, Tracy K.; Professor; Neurosurgery; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 01-JUN-1988; Project End 30-NOV-2003 Summary: (adapted from the abstract): Using established models of both uncompensated hemorrhagic hypotension (HH), traumatic brain injury (TBI) and a combined hemorrhage/brain injury paradigm (HH-TBI), this application proposes (1) to characterize and elucidate the role of cell death/survival genes, cytokines and alterations in DNA damage detection and repair mechanisms in mediating central nervous system (CNS) dysfunction following hemorrhage and mechanical injury and (2) evaluate novel pharmacotherapeutic strategies targeted at these pathways in the treatment of shock and trauma. The central hypothesis is that cellular death and dysfunction in the brain after shock or trauma is due to an up regulation of deathinducing genes (such as bax, capase-3, interleukins, TNF-alpha) and a downregulation of neuroprotective genes (such as Bcl-2, Bcl-xL), and that molecular changes in the brain following the single insults will differ from those observed following combined shock and brain trauma. Specific Aim 1 will use in situ hybridization/ immunohistochemistry to evaluate how HH or TBI results in an alteration in the balance (ratio) of cell death/survival genes in the brain which contribute to apoptotic cell death following these insults. The response of transgenic animals, genetically engineered to over express the anti-apoptotic gene bcl-2, to HH or TBI and the efficacy of pharmacologic inhibition of the pro-apoptotic protein caspase-3 will be evaluated. Specific Aim 2 evaluates gene expression of inflammatory cytokines in the rat brain following HH, TBI or HH-TBI to characterize the role of inflammatory cascades in mediating CNS dysfunction. Transgenic mice, genetically engineered to be deficient in expression of TNF-a (TNF-/mice), will be used to validate the hypothesis; and the therapeutic efficacy of recombinant human interleukin-18 receptor antagonist to inhibit cytokine function will be evaluated. Specific Aim 3 will evaluate the effects of HH, TBI or HH-TBI on endogenous DNA damage detection and repair mechanisms (activation of PARP). PARP knockout mice (PARP KO) will be used to validate out hypothesis that these insults alter DNA repair mechanisms which contributes to cell death and dysfunction. Pharmacologic inhibition of PARP will also be evaluated. Specific Aim 4 use single-cell aRNA amplification techniques to obtain expression profiles of multiple genes from neurons exhibiting DNA fragmentation in rat brain following HH, TBI or HH-TBI to establish the coordinated genomic changes that may play a role in cell death and dysfunction. Taken together, these studies will significantly enhance understanding of the molecular response in the CNS to hemorrhage shock, TBI, and combined injury and will result in the development of more effective therapeutic approaches to the treatment of shock and trauma. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CENTRAL HEMORRHAGE
NEURONAL
MECHANISMS--DECOMPENSATED
Principal Investigator & Institution: Guyenet, Patrice G.; Professor and Chair; Pharmacology; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904 Timing: Fiscal Year 2002; Project Start 01-APR-1999; Project End 31-MAR-2004
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Summary: Mild hemorrhage produces autonomic and endocrine compensatory responses that are able to greatly minimize hypotension. These well- known responses are mostly caused by unloading of arterial barorceptors and include withdrawal of cardiovagal tone and a vigorous activation of the sympathetic outflow. If hemorrhage is more severe the autonomic compensatory mechanisms are paradoxically reversed. This second or ~ decompensatory~ phase of hemorrhage is characterized by bradycardia and a sharp decrease of sympathetic activity ( hemorrhage-induced sympathoinhibiton. HiSI) that produce further cardiovascular deterioration. Initiation of the decompensatory phase has been attributed to the activation of vagal afferent from the cardiopulmonary region however the central pathways of HiSI are not known. Nevertheless several studies have suggested that CNS opiod peptides may play a key role in genesis of this phenomenon. The objective of the proposed work is to investigate the CNS portion of the circuitry involved in hemorrhage induced sympathoinhibition and bradyardia. The study will be divided into five parts. Aim 1: using an established anestheized rat model, we will determine whether HiSI can be explained by a reduction in the discharge rate of the vasomotor neurons of the rostral ventrolateral medulla. Aim 2: we will determine whether hypotensive hemorrhage activates CVLM GABAergic neurons that arborize in RVLM. We will also determine whether the CVLM region is necessary for HiSI to occur. Aim 3: we will determine whether hypotensive hemorrhage reduces central respiratory drive and whether this effect contributes to HiSI Aim 4: we will determine whether the release of opioid peptides in RVLM contributes to hiSl Aim 5: we will determine which CNS neurons are activated by hypotensive hemorrhage in conscious rats and whether they are opiodergic or GABAergic. Understanding the neurophysiological mechanisms triggered by hypotensive hemorrhage should lead to improved ability to manage this all too frequent clinical problem. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CEREBRAL FUNCTION AFTER HYPOTHERMIC CIRCULATORY ARREST Principal Investigator & Institution: Griepp, Randall B.; Chief, Div of Cardiothoracic Surgery; Cardiothoracic Surgery; Mount Sinai School of Medicine of Nyu of New York University New York, Ny 10029 Timing: Fiscal Year 2002; Project Start 01-SEP-1991; Project End 31-JUL-2004 Summary: This proposal is for ongoing study of ways to improve cerebral protection during operations on the heart and great vessels which require arrest of antegrade circulation. Clinical and experimental data suggest that subtle cerebral injury occurs if the duration of hypothermic circulatory arrest (HCA) is more than 30 minutes even under optimal circumstances, and some complex procedures cannot reliably be completed in so short a time. In our porcine experimental model, the effect of strategies such as retrograde cerebral perfusion (RCP) can be studied to see whether they can be used to extend the safe duration of HCA to 60 minutes. In this clinically relevant model, the effect of changes in the implementation of HCA and RCP on cerebral blood flow, cerebral metabolism, intracranial pressure, electrophysiological recovery, behavioral outcome (including preservation of ability to learn conditioned reflexes) and cerebral histopathology can be used to see whether new approaches, such as use of lower temperatures, postoperative ultrafiltration, cold reperfusion, and treatment with various pharmacological agents are likely to improve neurological outcome after operations requiring HCA. The hypothesis that some of the cerebral injury following HCA/RCP is occurring as a consequence of apoptosis, or programmed cell death, opens up the possibility of arresting this suicidal cascade using specific inhibitors of the proteases and
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endonucleases which participate in this process as well as inhibitors of protein synthesis, all of which have had dramatic success in reducing injury in rodent models of cerebral ischemia. The results of this study will make a significant contribution toward improving long-term outcome of complex surgery on the heart and great vessels in both infants and adults. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CHARACTERIZATION TRANSPORTER
OF
THE
ANANDAMIDE
UPTAKE
Principal Investigator & Institution: Rademacher, David J.; Pharmacology and Toxicology; Medical College of Wisconsin Po Box26509 Milwaukee, Wi 532260509 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2006 Summary: (provided by applicant): Some very exciting and important pathophysiological roles for the anandamide/cannabinoid receptor signaling system have been identified. Cannabinoid receptor activation by anandamide has been implicated in hemorrhagic hypotension, endotoxin-induced septic shock, pain perception, neuroprotection, and the alleviation of spasticity in a variety of conditions. The anandamide/cannabinoid receptor signaling pathway is important for normal embryonic fertilization, implantation, and development. The purpose of the present research is to provide for a better understanding of the biochemistry of anandamide inactivation through an uptake carrier. This will be accomplished by: (a) Measuring the accumulation of anandamide in a model devoid of intracellular binding sites and fatty acid amide hydrolase (FAAH); (b) Determining under what conditions, cell types, and to what extent a coupling between anandamide uptake and FAAH activity occurs; and (c) Isolating, purifying, and sequencing an intracellular anandamide binding protein. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CHRONIC MONITORING OF ISCHEMIC MODELS OF SUDDEN DEATH Principal Investigator & Institution: Smith, William M.; Professor; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2003 Summary: Most sudden cardiac death (SCD) is associated with coronary artery disease, but little is known about the exact sequence of events that leads up to it and the mechanisms responsible for it. There is a complex interplay between old myocardial infarcts, acute ischemia, the status of the autonomic system, mechanical viability, and electrophysiology that leads to SCD and influences whether tachycardia or bardycardia is the final rhythm. In this project, it is proposed to combine a unique set of technological and physiological resources to study the events surrounding sudden death. An animal model of infarct/ischemia leading to spontaneous SCD has been developing and will be studied in two complementary ways. One set of animals will be instrumented with a custom-developed telemetry system to acquire electrophysiologic and functional data during the conscious, ambulatory state, eliminating the confounding effects of thoracotomy and anesthesia and anesthesia on the incidence and nature of sudden death. Another set of animals will be studied with high resolution, three dimensional mapping to elucidate the mechanisms of the spontaneous arrhythmias that lead to SCD. It is hypothesized that the balance between the vagal and sympathetic arms of the autonomic system and that changes in repolarization properties of the myocardium are predictors of which animals die suddenly and spontaneously
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and spontaneously as well as the mode of death. It is also hypothesized that spontaneous tachycardia/fibrillation is initially reentrant and that the old infarct is involved in the arrhythmia maintenance. Further, it is hypothesized that bradycardia is associated with pump failure rather than a vagal reflex leading to hypotension. It is proposed to use the data from this research to develop, implement and validate measures that predict imminent SCD on the time scale of seconds to minutes. Because of the continuous nature of data acquisition over several days when no sustained arrhythmias are observed, it will be possible to determine the specificity as well as the sensitivity of derived predictors. Innovations in telemetry capability, cardiac mapping, and new animal models of spontaneous sudden cardiac death will provide information about the context and mechanisms of sudden death that has not been available before. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SYNDROME
CIRCULATORY
DYSFUNCTION
IN
CHRONIC
FATIGUE
Principal Investigator & Institution: Stewart, Julian M.; Professor; Pediatrics; New York Medical College Valhalla, Ny 10595 Timing: Fiscal Year 2002; Project Start 24-AUG-2001; Project End 31-JUL-2005 Summary: Chronic fatigue syndrome (CFS) is associated with orthostatic intolerance which often takes the form of postural orthostatic tachycardia syndrome (POTS) in adolescents. Preliminary data suggest the novel concept that defective vasoconstriction produces POTS in CFS with cardiac autonomic changes as a secondary response. CFS patients will be compared to healthy controls and to controls with simple faints to test 3 hypotheses: 1) Blood is redistributed peripherally and redistribution is enhanced during orthostasis producing increased microvascular filtration and dependent edema. Central hypovolemia causes decreased cardiac output, reflex tachycardia and reduced cerebral blood flow. This is enhanced during orthostasis producing increased microvascular filtration, dependent edema, and peripheral pooling. These changes alter the interstitium, and cause reflex tachycardia, reduced cerebral blood flow and often hypotension. Blood volume and cardiac output using the indocyanine green dye dilution technique will be measured supine, during conventional 700 head-up tilt, and during low angle head-up tilt. Cerebral blood flow velocity (CBFv) will be estimated by transcranial Doppler ultrasonography. Thoracic, splanchnic, and pelvic vascular volumes will be measured by impedance plethysmography, and limb blood flow, arterial flow, venous volume-pressure relation, and venous pressure will be measured by venous occlusion strain gauge plethysmography. These will show increased blood flow to lower extremities when upright. Central hypovolemia will occur and will reduce CBF and produce symptoms of CFS. Cardiac autonomic status including baroreflex will be assessed by heart rate and blood pressure variability and transfer function. Baroreflex and heart rate variability will be decreased and blood pressure variability will be increased related to circulatory deficit 2) The defect in vasoconstriction is heterogeneous comprising abnormal arterial baroreflex mediated sympathetic vasoconstriction in one subgroup of CFS patients and abnormal local vasoconstriction in a second subgroup with defective veno-arteriolar reflex (arterial baroreflex insensitive dysfunction). Low angle tilt will be used to activate baroreflex mediated and local reflexes. Local reflexes including myogenic, metabolic and veno-arteriolar will be sorted out through use of supine testing designed to specifically stimulate a specific reflex (limb hang, large pressure step and reactive hyperemia) and measuring peripheral resistance. 3) Cardiac autonomic findings are secondary to circulatory changes. Thus, tachycardia relates to vagal withdrawal because of circulatory insufficiency. CFS patients will be treated with
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midodrine or placebo in a cross-over study. Using supine and low angle tilt experiments, circulatory measurements and psychological instruments will be combined to demonstrate that circulatory abnormalities, autonomic abnormalities and symptoms correct in a subgroup of CFS patients with low resting peripheral resistance. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CIRCULATORY TETRAHYDROBIOPTERIN
SHOCK,
NITRIC
OXIDE
AND
Principal Investigator & Institution: Gross, Steven S.; Professor; Pharmacology; Weill Medical College of Cornell Univ New York, Ny 10021 Timing: Fiscal Year 2002; Project Start 01-JUL-1994; Project End 31-MAY-2004 Summary: Nitric oxide (NO) is a potent endothelium-derived vasodilator that serves a physiological role in the regulation of blood pressure and vascular tone. Immunostimulants, such as bacterial lipopolysaccharide (LPS), act on many mammalian cell types to trigger transcription of the gene encoding the inducible form of NO synthase (iNOS). In the blood vessel, this results in NO over-production, hypotension and often vascular collapse and death. Induction of iNOS is considered to be the etiological basis for septic shock, a condition caused by systemic bacterial infection and which is the leading cause in intensive care units throughout the U.S.A. While iNOS gene expression is necessary for LPS-induced hypotension, we now know that is not sufficient. Indeed, immunostimulants also act on vascular cells to induce expression of GTP cyclohydrolase I (GTPCH), the rate limiting enzyme for the synthesis of the essential NOS co-factor, tetrahydrobiopterin (BH4). Immunostimulant- induced NO synthesis in vascular cells can be prevented by inhibitors of BH4 synthesis and accelerated by provision of exogenous BH4. Thus, BH4 availability limits iNOS activity. During the initial grant period, we cloned the GTPCH gene and found its transcription is upregulated by immunostimulants in vascular smooth muscle. However, additional important mechanisms have been uncovered that may have profound impact on intracellular levels of BH4. The overall goal of the proposed research is to elucidate how intracellular levels of BH4. The overall goal of the proposed research is to elucidate how intracellular levels of BH4 are regulated in vascular smooth muscle cells and how BH4 functions for iNOS catalysis. Toward this end, Specific Aims of our research are: 1) to specify post-translational modifications of GTPCH regulation by "GFRP", a recently cloned GTPCH-binding protein that serves to balance BH4 with cellular needs; 3) to characterize processes that mediate cellular uptake and efflux of reduced pterins and the contribution of pterin transport to regulation of BH4 levels in vascular smooth muscle; 4) to elucidate structural requirements of pterin analogs for binding and function in iNOS catalysis. These studies will improve our understanding of BH4 regulation and function and may provide insights that lead to novel biopterin-based strategies for pharmacotherapy of septic shock and other conditions arising from NO excess. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CNS AUTONOMIC REGULATION BY ELECTROACUPUNCTURE Principal Investigator & Institution: Longhurst, John C.; Professor; Medicine; University of California Irvine Irvine, Ca 926977600 Timing: Fiscal Year 2002; Project Start 20-SEP-2000; Project End 31-DEC-2003 Summary: (Adapted from Applicant's Abstract): Acupuncture is an effective therapeutic modality in Eastern cultures, but has not achieved widespread recognition as a useful therapeutic option in Western medicine. In addition to its use in pain and anesthesia,
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electro-acupuncture (EA) has been used in hypertension, hypotension, angina and cardiac arrhythmias. Recently, the Pl's laboratory has begun to explore the physiological basis of EA. An initial study demonstrated that low frequency EA ameliorates myocardial ischemia by reducing myocardial oxygen demand in a feline model of reversible ischemia. In this model, stimulation of gallbladder chemosensitive afferent nerve endings reflexly increased arterial blood pressure, and augmented myocardial oxygen demand, which outstripped coronary blood supply following partial coronary ligation. Concurrent stimulation of the median nerves underlying the Neiguan acupoints reduced myocardial ischemia, measured as a reduction in regional wall thickening. A second study employing EA suggests a role of the endogenous opiate system in the rostral ventral lateral medulla (rVLM). Preliminary data from the Pl's laboratory indicate that the rVLM and periaqueductal gray (PAG) mediate the interaction between visceral (gallbladder) and somatic (EA) afferent nerve stimulation, and suggest a role for mu- and delta-opioid receptors. Also, the Pl has demonstrated in preliminary studies the ability to identify cells in the rVLM that receive convergent input from the greater splanchnic nerve (supplying the gallbladder) and the median nerve. Five hypotheses are now proposed: 1 ) The order of potency for the blood pressure-lowering effect of EA will be mu-equal to or greater than delta-greater than kappa-opioid receptors; 2) Non-NMDA excitatory amino acid receptors are responsible for stimulation of its neuronal subpopulation; 3) EA of Neiguan produces post-synaptic inhibition of an excitatory input to these neurons; 4) The ventrolateral PAG participates in EA modulation of reflex autonomic responses through an opioid mechanism and by influencing sympathoexcitatory rVLM neurons; and 5) Deep but not superficial somatic nerves underlying specific acupoints provide convergent input into rVLM and PAG neurons, and, through an opioid mechanism, modulate neuronal activity. Studies will be conducted in anesthetized cats whose rVLM and PAG are approached stereotaxically for extracellular recording and to deliver pharmacologic antagonists and agonists. Collaboration with both US and Chinese authorities on central neural electrophysiological and acupuncture research will significantly contribute to the ability to accomplish this investigation. By demonstrating the central neural mechanisms underlying this clinically beneficial modification of a cardiovascular reflex response by EA, scientists and clinicians will have a better understanding that will likely aid in acceptance and use of this alternative therapy. The Pl indicates that this project has important clinical implications. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CONSEQUENCES OF CHRONIC RENAL INSUFFICIENCY Principal Investigator & Institution: Hsu, Chi-Yuan; Medicine; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 30-JUN-2007 Summary: (provided by applicant) Currently 300,000 Americans suffer from end-stage renal disease (ESRD), which is associated with substantial morbidity and mortality. Recent data suggest there is a much larger number of individuals who have impaired kidney function not requiring dialysis or transplantation (i.e., chronic renal insufficiency). However, the health consequences and public health burden of chronic renal insufficiency (CRI) are incompletely defined. We hypothesize that the relationship between CRI prevalence and subsequent ESRD incidence varies across demographic and disease subgroups because of differences in rates of decline of renal function and competing mortality risks. We hypothesize that the metabolic and homeostatic disturbances of CRI lead to osteopenia, periodontal disease and blood pressure
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elevation. Expression of these consequences of CRI may be influenced by dietary factors such as intake of sodium, calcium and other dietary components. We hypothesize that CRI is associated with reduced physical functioning. We will analyze the nationally representative Second (1976-80) and Third (1988-94) National Health and Nutrition Examination Survey (NHANES II and III) databases which contain information on renal function as well as detailed assessment of health and nutrition status. We will use the nationwide and comprehensive US Renal Data System ESRD registry (1988-present) to examine the relationship between CRI prevalence and subsequent ESRD incidence in specific birth cohorts. We will collect longitudinal data on physical functioning, body composition and nutritional status in a separate cohort of CRI subjects. Linear, logistic and Poisson regression and longitudinal data analysis techniques will be used to assess the independent association of CRI with outcomes. The overall objective of this application is to support my development in a career focused on patient-oriented research in nephrology. To accomplish this objective, the proposed program has both scientific and career development components. The scientific component is outlined above. The first career development objective is to strengthen my analytic skills and increase my sophistication as a clinical researcher through formal course work, directed reading and one-on-one tutorials. The second career development objective is to obtain training in creating and following a cohort of subjects with CRI and conducting primary data collection. These will contribute greatly to my development into an independent investigator. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: COUPLING MECHANISMS OF OP4 RECEPTOR AND CALCIUM CHANNELS Principal Investigator & Institution: Ruiz-Velasco, Victor J.; Anesthesia; Pennsylvania State Univ Hershey Med Ctr 500 University Dr Hershey, Pa 17033 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2007 Summary: (provided by applicant): The long-term objective of this proposal is to understand how opioid receptors, present in rat sympathetic stellate ganglion (SG) neurons innervating the heart, couple to calcium channels involved in neurotransmitter release. This project will focus on a newly identified opioid receptor (OP4) that is activated by nociceptin (NOC). Noc-mediated OP4 receptor activation elicits cardiovascular responses such as bradycardia and hypotension via pathways that influence the autonomic nervous system--mostly through an inhibition of neural transmission. A combination of etectrophysiological, molecular, optical and biochemical techniques will be used to probe the mechanisms whereby Noc-activated OP4 receptors modulate N-type calcium channels. The specific aims of the proposal are to: (i) identify the specific Galpha subunit that couples OP4 receptors to N-type calcium channels; (ii) examine the kinetic role which regulators of G protein signaling (RGS) proteins play in Noc-mediated calcium channel inhibition; (iii) investigate whether OP4 receptors are capable of forming homo- or hetero-oligomers. OP4 receptors play an important role in the autonomic nervous system pathways that contribute to heart rate and blood pressure regulation. The proposed studies will help to clarify the signaling mechanisms underlying these processes and facilitate the development of novel cardiovascular agents for treating hypertension resulting from increased sympathetic tone. Moreover, the information gathered from these studies may help determine the precise role opioids play in decreasing myocardial infarct size. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DEVELOPMENT OF POLY-L-GLUTAMIC ACID PACLITAXEL CONJUGATE Principal Investigator & Institution: Wallace, Sidney; Fem Cadet 3324 Pittsburgh St Houston, Tx 77005 Timing: Fiscal Year 2002; Project Start 15-APR-1999; Project End 31-MAY-2006 Summary: Chemoradiation improves survival for patients with locally advanced nonsmall cell lung cancer (NSCLC) over radiotherapy (R) alone. Les than 20% of patients have complete pathologic response to combination therapy. Paclitaxel (TXL) is effective as an anti-tumor agent and a radiosensitizer. Peripheral neurotoxicity and granulocytopenia limit its dosage; acute effects from TXL's infusion include nausea, hypotension, and cardiac arrhythmias related to Cremophor and ethanol. Conjugating TXL with poly-L-glutamate (PG-TXL/CT-2103) makes it water-soluble, allowing infusion of twice the amount of free TXL and higher intratumoral drug concentrations, which was confirmed by preclinical testing. Combining PG-TXL with radiation demonstrated synergistic radiation enhancement higher than that seen with other taxane or nucleoside analog. A phase I clinical trial of CT-2103 as single agent salvage therapy for patients with advanced solid tumors demonstrated safety and tolerability in dose up to 266 mg equivalent paclitaxel/m2 without significant alopecia. This Phase II STTR proposes a Phase I/II clinical trial of CT-213 given concurrently with chest RT in patients with unresectable Stage III or medically inoperable Stage II NSCLC. This study will determine MTD, DLT, pharmacokinetics, assess toxicity, and document patient costs. We expect this combination RT and CT-2103 to improve patient survival and response to treatment. PROPOSED COMMERCIAL APPLICATIONS: At M.D. Anderson Cancer Center, the combination of Taxol and cisplatin given concurrently with radiation therapy is the treatment of choice for lung cancer patients. In animal studies, CT-2103 is water soluble, infectable intravenously in 10 minutes without premedication, more effective (2-3X) and less toxic than Taxol. CT-2103 could possibly replace Taxol. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DEVELOPMENTAL BIOLOGY AND PATHOLOGY CENTER Principal Investigator & Institution: Kinney, Hannah C.; Associate Professor; Children's Hospital (Boston) Boston, Ma 021155737 Timing: Fiscal Year 2003; Project Start 26-SEP-2003; Project End 31-JUL-2006 Summary: (provided by applicant): This application is a response to the Request for Application (RFA) entitled: Prenatal Alcohol Exposure Among High-Risk Populations: Relationship to Sudden Infant Death Syndrome (SIDS) (RFA: HD-03-004). Our group is applying for the award of the Developmental Biology and Pathology Center. As requested in the RFA, we plan to conduct basic and applied research related to molecular and biological aspects of alcohol related injury to the brain, systemic organs, and placenta in the subject population. We hypothesize that prenatal exposure to alcohol adversely affects the development of the serotonergic (5-HT) system in the medulla oblongata of the brainstem, and thereby puts the vulnerable fetus/infant at risk for sudden death by compromising an array of homeostatic reflexes which are all influenced by the medullary 5-HT neurons, and which protect the fetus/infant from lifethreatening stressors, e.g., hypoxia, hypercarbia, and hypotension. This hypothesis is a direct outgrowth of our brainstem analysis in two independent databases of SIDS and control cases, including in the Northern Plains Indians, a high-risk population. We propose 5 Specific Aims for the sample study to examine inter-relationships between
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Hypotension
brainstem 5-HT and vasoactive intestinal peptide (VIP), the latter shown to play a pivotal role in the pathogenesis of alcohol-induced injury in animal models. In Specific Aim 1 we will determine if abnormalities in the medullary 5-HT system correlate with VIP abnormalities in this system in fetuses and/or infants with sudden death who were exposed to prenatal alcohol. In Specific Aim 2, we will determine if markers of oxidative stress correlate with5-HT-related abnormalities in the medullary 5-HT system in such fetuses/infants. In Specific Aim 3, we address the question if the same brainstem abnormalities reported by us in SIDS infants are present in unexplained stillbirth, data which would substantiate the idea that there is a continuum of disease-effect from the fetal period through infancy. In Specific Aim 4, we seek to know if polymorphisms or mutations in 5-HT-related markers are associated with medullary 5-HT system abnormalities and an increased risk for sudden death in fetuses/infants exposed to prenatal alcohol. In Specific Aim 5, we address issues related to VIP expression in the placenta, the key organ of maternal-fetal homeostasis, based upon reports of alcoholinduced reductions in placental VIP in animal models. These human studies should help provide the necessary critical steps to translate basic science findings into therapeutic strategies for the prevention or amelioration of prenatal alcohol-induced injury to the developing human brain. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DIABETIC AUTONOMIC NEUROPATHY Principal Investigator & Institution: Low, Phillip A.; Professor; Mayo Clinic Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 31-AUG-2004 Summary: The pathogenesis and pathophysiology of diabetic autonomic neuropathy is poorly understood and its treatment unsatisfactory. Autonomic dysfunction of IDDM may be different to that of NIDDM, but studies to date have been limited by significant selection bias and the instruments to evaluate symptoms and autonomic dysfunction have not been available. We will undertake a population-based study to test the hypothesis that autonomic symptoms and deficits in the neuropathy of IDDM are different to those of NIDDM, with greater involvement of the splanchnic- mesenteric bed in IDDM. In this study we will evaluate autonomic symptoms using our validated instrument, the autonomic symptom profile, in the entire cohort of 322 patients (IDDM and NIDDM; Specific aim number 1) in the Rochester Diabetic Project (Director: Peter Dyck). This autonomic symptom profile will be combined with a laboratory profile of cardiovagal, adrenergic and sudomotor dysfunction, and by laboratory evaluation of the splanchnic-mesenteric, systemic, and cerebrovascular beds, catecholaminergic responses, and gastric transit and accommodation studies (Specific aim number 2). Mesenteric blood flow will be measured using 2-D doppler ultrasound, cerebral perfusion using transcranial doppler, beat-to-beat BP using Finapres, and heart rate from electrocardiographic monitor. Whether a patient develops symptoms of orthostatic hypotension depends on cerebral autoregulation, a process whereby cerebral perfusion remains unchanged in the face of changing systemic BP. We hypothesize that the autoregulatory slope relating the change in cerebral perfusion to that of blood pressure (BP) (deltaBFV: deltaBP), and is an index of autoregulatory adaptation, changes with duration and severity of orthostatic hypotension in diabetic autonomic neuropathy. We will evaluate cerebrovascular autoregulatory adaptation in patients with IDDM and NIDDM (Specific aim number 3). Treatment of diabetic orthostatic hypotension with alpha-agonists or fludrocortisone cause or aggravate supine hypertension. This is a particular problem in diabetics, who have increased small and large vessel
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atherosclerotic disease. We will evaluate if cholinesterase inhibition, by increasing ganglionic neurotransmission, will, by restoring transmission of some fibers, and amplify the efficiency of residual baroreflexes, improve orthostatic hypotension without supine hypertension (Specific aim number 4). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DOPA D3 RECEPTOR AGONIST POTENTIAL ANTIGLAUCOMA AGENT Principal Investigator & Institution: Chu, Teh-Ching; Pharmacology and Toxicology; Morehouse School of Medicine Atlanta, Ga 30310 Timing: Fiscal Year 2002; Project Start 01-AUG-2000; Project End 31-JUL-2004 Summary: Dopamine is a major neurotransmitter in central nervous system and retina. Recently, dopamine D3 preferring receptor agonists have been proposed for the treatment of neuropsychiatric disorders such as schizophrenia and Parkinson's disease. Although the potential of D2 receptor agonists as intraocular pressure (IOP)-lowering agents has been investigated, the therapeutic value has not been determined. Research in this laboratory has revealed that topically administered 7-OH-DPAT, a D3 preferring receptor agonist, lowered IOP bilaterally in rabbits. To understand the ocular action of D3 agonists, the mechanism(s) of IOP-lowering effects will be examined. Long-term objectives: 1) to ascertain the sites of action whereby aqueous humor inflow/outflow are regulated by D3 agonists, 2) to elucidate the cellular mechanisms for the ocular hypotension induced by D3 agonists and 3) to determine the mechanisms of neuroprotection provided by D3 agonists. Hypotheses: D3 preferring receptor agonists: 1) lower IOP by modifying aqueous inflow/outflow through interaction with cellular function of sympathetic neurons and 2) antagonize the glutamate-induced toxicity of retinal ganglion cells. Specific aims: 1) characterize the effects on norepinephrine release from sympathetic nerve endings of ciliary body, 2) determine sites of action of D3 agonists by evaluating effects on norepinephrine release from sympathetic nerve endings of ciliary body, 3) determine which signal transduction mechanisms are suppressed by D3 agonists in sympathetic retinal ganglion cells. Tonometry, fluorophotometry, two-stage constant pressure perfusion, immunohistochemistry, radioimmunoassay, image analysis and patch-clamp will be utilized to accomplish the specific aims. The goal of this project is to provide evidence for the sites and mechanisms of potential antiglaucoma agents (D3 agonists) and to define, more specifically, the potential role(s) of these compounds in modulating ocular hydrodynamics and neuroprotection. This research should provide significant leads to the discovery of novel therapeutic agents (D3 agonists) for the treatment of chromic, open-angle glaucoma. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DOPAMINE/GLUTAMATE AND HYPOXIC INJURY IN NEWBORN BRAIN Principal Investigator & Institution: Wilson, David F.; Professor of Biochemistry and Biophysics; Biochemistry and Biophysics; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 01-JUL-1992; Project End 31-AUG-2004 Summary: (Adapted from the Investigator's Abstract): Experimental models will induce carefully controlled levels of brain hypoxia, quantitated by direct measurement of oxygen levels in the tissue microcirculation, followed by periods of reoxygenation.
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These models will include brain hypoxia induced by arterial hypoxia (decreased FiO2; a high flow hypoxia) and hemorrhagic hypotension with bilateral carotid occlusion (a low flow hypoxia). The mechanism(s) of cellular dysfunction and/or injury will be examined at both the cellular and molecular levels. Changes in extracellular levels of glutamate and dopamine will be continuously monitored by in vivo microdialysis. The brain tissue will be screened for multiple genes that may be altered in expression level as the results of the hypoxic/ischemic episodes and reoxygenation. This will be performed using the amplified antisense RNA (aRNA) technique, and genes selected for analysis will correspond to proteins that are implicated as key points in dopamineglutamate interactions. The role of dopamine, and of dopamine and glutamate receptors on the number of cells undergoing apoptosis and/or necrotic cell death will also be determined by the TUNEL technique. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DOPAMINE-B-HYDROXYLASE IN HUMAN CARDIOVASCULAR CONTROL Principal Investigator & Institution: Robertson, David H.; Professor of Medicine, Pharmacology And; Medicine; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2003; Project Start 01-FEB-2003; Project End 31-JAN-2007 Summary: (provided by applicant): Norepinephrine (NE) is the critical pressor determinant in neural regulation of blood pressure, while dopamine (DA) plays an important depressor role via renal and plasma volume mechanisms. Dopaminebetahydroxylase (DBH) is the enzyme responsible for the conversion of DA to NE. Great interindividual variation exists in plasma levels of DBH with heritability estimated at 0.9. Polymorphisms in the DBH gene associate with low DBH levels and activity. We reported the extreme example of complete DBH deficiency, a genetic condition in which no functional DBH appears to exist. These patients lack NE and its metabolites both centrally and peripherally but have greatly elevated plasma DA and DOPA. They suffer from severe orthostatic hypotension, hypovolemia, and ptosis of eyelids. Among individuals with low plasma DBH, abnormalities in NE/DA balance might contribute to perturbations in blood pressure and heart rate control. Individuals with low DBH activity might have higher levels of plasma DA under conditions of stress, resulting in hypotension, due to vasodilatation, hypovolemia, or other mechanisms. The relationship of DBH enzyme activity to interindividual variation in cardiovascular control will be evaluated by assessment of baseline and stimulated DBH levels and sympathetic nervous system function in healthy volunteers (selected by DBH genotype) and in patients with orthostatic intolerance, familial dysautonomia, and pheochromocytoma. All subjects will be genotyped for DBH genetic polymorphisms. Study participants will undergo various levels of sympathetic stress in an effort to overwhelm their endogenous DBH capacity and raise plasma DA levels. A pharmacological model of partial DBH deficiency in human subjects will be developed to discover the likely autonomic cardiovascular phenotype. These studies should elucidate the role of DA in blood pressure control in healthy subjects and in certain disease states, and may lead to important advances in their management. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: EFFECTS OF O2 RADICALS AND PERIVASCULAR NERVES IN TRAUMA Principal Investigator & Institution: Dewitt, Douglas S.; Professor; Anesthesiology; University of Texas Medical Br Galveston 301 University Blvd Galveston, Tx 77555 Timing: Fiscal Year 2002; Project Start 01-DEC-1986; Project End 31-JAN-2004 Summary: (Verbatim from the Applicant's Abstract) Traumatic brain injury (TBI) increases cerebral vascular resistance, damages cerebral vascular endothelial cells and the blood brain barrier and reduces cerebral vasodilatory responses to hypotension, hypoxia and hemodilution. Our overall hypothesis is that traumatic brain injury increases superoxide anion radicals which react with increased NO to form OONO-, impairing the function of cerebral vascular smooth muscle and perivascular nerves. Aim 1 is to determine the association between NO, O2-, and CBF decreases after traumatic brain injury. NO, superoxide, and CBF will be measured in rats after moderate traumatic brain injury. Studies will be done to see if arginine supplementation restores CBF despite increases in O2- production. Immunohistochemical staining for nitrotyrosine will be used to determine if TBI and L-arginine treatment increases OONO- production. Aim 2 is to determine if traumatic brain injury reduces the activity of eNOS and/or increases the potentially damaging iNOS and nNOS isoforms, using arginine to citrulline conversion assays with specific inhibitors and mRNA expression studies. Aim 3 is to determine if traumatic brain injury affects the cerebral vascular responses to endothelium-dependent vasodilator ACh, activators of ATP-sensitive potassium channels like aprikalim, or reduced perfusion pressure, using arteries harvested following traumatic brain injury. Aim 4 is to determine the effects of TBI and OONO- exposure on perivascular vasodilatory neurotransmitters CGRP, ACh, and anadamide. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: EFFECTS OF VASOACTIVE DRUGS ON PERFUSION IN SEPTIC SHOCK Principal Investigator & Institution: Murray, Patrick T.; Anesthesia and Critical Care; University of Chicago 5801 S Ellis Ave Chicago, Il 60637 Timing: Fiscal Year 2002; Project Start 01-AUG-2001; Project End 31-JUL-2006 Summary: (provided by applicant): This Mentored Patient-Oriented Research Career Development Award application requests support (or a proposal which includes mentorship by an experienced investigator, multidisciplinary support from the Chairs and faculty of several Departments. formal training in an NIH-funded Clinical Research Training Program. and a research project dissecting the regional and systemic effects of traditional and novel vasoactive drugs in critically ill patients with septic shock. Sepsis. the systemic inflammatory response to infection. may lead to refractorv hypotension (septic shock) and multiple organ system failure (MOSF). Despite increased cardiac output and oxygen delivery, death often ensues from refractory hypotension or subsequent MOSF. Standard indicators of adequate tissue perfusion which are used to titrate therapy in hypovolemic or cardiogenic shock are unreliable in hyperdynamic septic shock. Rational septic shock therapy would preferably be guided by targeted interventions tc? optimize end-organ perfusion and function, and reverse detectable tissue hypoperfusion. The primary end-organ index of adequate perfusion used in current clinical practice is renal perfusion and function. The effects of vasoactive drug therapy on renal perfusion and function are reliably quantifiable with sophisticated existing technology. This application seeks to determine the regional circulatory effects
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Hypotension
of restoring vascular contractility with standard exogenous catecholamines and the novel use of exogenous vasopressin, alone or in combination, in septic humans, focusing on renal perfusion and function. We will also examine the systemic and regional effects of targeted vasodilator therapy with fenoldopam (a novel dopaminergic agonist) in septic humans, alone or in combination with the aforementioned vasoconstrictors. Specifically, we will address the hypotheses that: 1) Addition of inotropic support (badrenoceptor stimulation) to intravenous fluids alone, or in combination with pure vasopressor therapy (a-adrenoceptor stimulation), improves renal perfusion and function in patients with sepsis or septic shock. 2) Titration of vasopressor therapy to a mean arterial pressure above the lower renal autoregulation threshold improves renal perfusion in patients with vasopressor-dependent septic shock. 3) Vasopressin therapy restores septic vascular contractility, augments vasopressor-responsiveness, reverses hypotension. and improves systemic and renal perfusion in human subjects receiving standard therapy for sepsis or septic shock. 4) Septic renal vasoconstriction is reversed, and renal perfusion and function improved, by selective renal vasodilator therapy. The overall aim of these experiments is to develop rational pharmacologic regimens and strategies for hemodynamic support in septic shock. focusing on prevention and management of septic acute renal failure, as a surrogate endpoint to optimize systemic perfusion in hyperdynamic states. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ESTROGEN & PROGESTERONE EFFECTS ON ORTHOSTATIC TOLERANCE Principal Investigator & Institution: Stachenfeld, Nina; John B. Pierce Laboratory, Inc. 290 Congress Ave New Haven, Ct 06519 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2006 Summary: (provided by applicant): Orthostastic intolerance is a dysfunction of the cardiovascular system that affects primarily young, healthy women. Diminished circulating blood volume and low peripheral resistance are primary mechanisms for orthostatic intolerance. Estrogen and progesterone modulate both plasma volume (PV) and peripheral vascular resistance (PVR). The purpose of this study is to compare PV regulation, PVR and orthostatic tolerance in women under four different hormonal conditions: when estrogen and progesterone are suppressed; when estrogen is elevated; when progesterone is elevated, and when progesterone and estrogen are elevated. The Specific Aims are: 1) To determine estrogen and progesterone modulation of extracellular fluid and protein distribution, and renal mechanisms controlling water retention. Plasma protein changes alter the colloid osmotic pressure gradient across capillaries and selectively enhance or reduce plasma volume. We hypothesize that estrogen acts on vessels to reduce vascular permeability to proteins, thereby reducing protein and fluid movement out of the vasculature and increasing PV. Moreover, we will test the hypothesis that estrogen and progesterone increase total extracellular fluid volume (ECFV) associated with renin-angiotensin-aldosterone system (RAAS)-mediated renal adjustments. Thus cardiovascular adjustments to postural changes may be improved when estrogen is elevated due to greater fluid retention and due to selective fluid retention in the plasma. We also hypothesize that PV expansion is the consequence of ECFV expansion when progesterone is increased concomitant with estrogen. High progesterone alone may reduce PV both by reducing colloid osmotic pressure gradient across capillaries and by attenuating aldosterone actions on the kidney, reducing water retention, and thus extracellular fluid and plasma volumes. 2) To test the hypothesis that estrogen-related reductions in PVR response to posture changes contribute to orthostatic
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31
intolerance in women, and progesterone antagonizes these estrogen mediated changes in PVR, helping to maintain orthostatic tolerance. These studies will define the impact of estrogen and progesterone on the interaction between blood volume and vascular resistance during orthostatic challenges, and thus may improve treatment of orthostatic intolerance in women. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EXERCISE TRAINING AND VAGAL-CARDIAC FUNCTION IN ELDERLY Principal Investigator & Institution: Shi, Xiangrong; Assistant Professor; Integrative Physiology; University of North Texas Hlth Sci Ctr Fort Worth, Tx 761072699 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 30-JUN-2006 Summary: (provided by applicant): It has been demonstrated in young adults that aerobic exercise training enhances cardiac parasympathetic (or vagal) nerve activity. This improved vagal-cardiac function is cardioprotective. Recently, we found that a compromised arterial blood pressure (ABP) regulation in elderly adults was associated with an age-related vagal dysfunction. Since aging is accompanied by chronic physical inactivity, questions remain as to whether aerobic exercise training can reverse the vagal dysfunction manifest in the elderly. We hypothesize that elderly adults with greater relative aerobic capacity will have greater autonomic neural control of the heart than their age matched counterparts and that the enhanced vagal-cardiac modulation resulting from exercise training will assist in APB stability at rest and during orthostatic challenge. We will test these hypotheses by evaluating vagally mediated control of cardiac function and baroreflex control of blood pressure in trained and in untrained elderly subjects aged 65 - 75 years. Selective muscarinic and beta1-adrenergic blockade will be used to determine the effects of endurance training on the specific neural area of the autonomic neural control of the heart affected by exercise training. Additionally, the effect of exercise training will be assessed by comparing untrained elderly subjects before and after one year of moderate intensity aerobic exercise training. Our long-term objectives are to understand the albeit regulatory mechanisms of blood pressure and blood volume due to age and to provide the basis for the use of prophylactic measure to improve the quality of human life. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: RESPONSES
FETAL
CARDIOVASCULAR
AND
ENDOCRINE
REFLEX
Principal Investigator & Institution: Wood, Charles E.; Professor and Interim Chair; Physiology and Functional Genomics; University of Florida Gainesville, Fl 32611 Timing: Fiscal Year 2002; Project Start 03-MAY-1996; Project End 31-MAR-2006 Summary: Baroreceptor and chemoreceptor reflexes are actively involved in the control of fetal blood pressure and in the maintenance of blood flow to the placenta and to the metabolizing tissues. The present project is an investigation into the mechanism of the baro- and chemoreflexes. In the first funding period of this project, we discovered an important interaction between endogenously generated prostanoids and reflex activity. During the initial funding period, we made the following conclusions: 1) Endogenous generation of prostanoids augment the reflex mechanisms controlling cardiovascular and endocrine responses to hypotension. 2) Neurons, as well as vasculature, contain the enzymes (PGHS-1, PGHS-2, and thromboxane synthase) needed for synthesis of prostanoids. These enzymes are found in neurons important for reflex control of the
32
Hypotension
cardiovascular system (in nucleus of the tractus solitarius, rostral and ventrolateral medulla, intermediolateral column of the spinal cord, paraventricular nucleus). There are ontogenetic changes in the concentrations of these enzymes. 3) PGE2 is released into the interstitial fluid of the brain and thromboxane A2 in released into the bloodstream during hypotension. 4) The so-call 'inducible' form of cyclooxygenase, PGHS-2, is upregulated at both the protein and mRNA level in fetal brain after hypotension. The upregulation of the protein for PGHS-2 is both in neurons and vasculature in the cardiovascular reflex-controlling regions of the fetal brain. 5) Injections of PGE2 or U46619 (thromboxane mimetic) into the cerebrospinal fluid of fetal sheep stimulates responses which are similar to the efferent responses to hypotension (vasoconstriction, secretion of adrenocorticotropin and vasopressin). These discoveries suggest that the production of prostanoids within afferent neural pathways stimulate or modulate reflex responses to cerebral hypoperfusion in the fetus. These findings have led us to propose the following specific aims, to propose to answer the following questions: 1) what are the relative contributions of PGHS-1 and PGHS-2 to the control of fetal reflex responses to hypotension? We will answer this question using both in vivo (chronicallycatheterized fetal sheep), and in vitro (enzymology) techniques. 2) Does sinoaortic denervation alter the expression and distribution of PGHS-1 and PGHS-2 in fetal brain and does sinoaortic denervation block the PGHS-2 response to hypotension? We will answer this question using immunohistochemistry and RT-PCR. 3) Does hypotension cause the phosphorylation of PGHS-2, rapidly increasing its activity? We will answer this question using immunoprecipitation and immunoblot techniques. 4) Do prostanoids inhibit chloride uptake by GABAA receptors? We will answer this question using synaptoneurosomes (chloride uptake), in situ quantitative autoradiography, and immunohistochemical co-localization studies. In the proposed 5-year continuation of this project, the answers to these questions will significantly enhance our understanding of the mechanism by which prostanoids act within the brain to alter cardiovascular function. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FUNCTIONAL MAPPING AND PROTEIN ENGINEERING OF THROMBIN Principal Investigator & Institution: Leung, Lawrence L.; Professor and Chief; Medicine; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2004; Project Start 01-JAN-1999; Project End 31-DEC-2007 Summary: (provided by applicant): Thrombin cleavage of osteopontin (OPN), an RGDcontaining proinflammatory cytokine, greatly augments its cell interactive properties by the exposure of a new alpha4beta1and alpha9beta1 integrin binding site SVVYGLR at its C-terminus. Both OPN and alpha4beta1 integrin are important in experimental autoimmune encephalitis (EAE), a mouse model of multiple sclerosis. We hypothesize that thrombin-cleavage of OPN, with its resultant enhanced interaction with alpha4beta1 inteqrin, is important in the pathogenesis of EAE. We showed that thrombin cleavage of recombinant OPN markedly increased the binding of Jurkat cells (which express alpha4beta1), and activated thrombin-activatable fibrinolysis inhibitor (TAFla) abolished this enhanced cell binding by cleaving the C-terminal arginine. TAFI is a latent plasma carboxypeptidase, which is activated by the thrombinthrombomodulin (TM) complex on endothelial cells. We showed that TAFla is more effective than plasma carboxypeptidase N in inactivating bradykinin (BK) and activated complement C5a. We hypothesize that TAFla is an anti-inflammatory molecule, which, together with aPC, counteract the proinflammatory effects of thrombin. E229K
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33
thrombin, an engineered human thrombin with minimal procoagulant functions, activated PC and TAFI in mice, and blocked BK-induced hypotension. Aim #1 Structure-function analysis of the thrombin-OPN interaction and TAFla inactivation of the SVVYGLR site. We shall characterize thrombin cleavage of soluble vs immobilized OPN and phosphorylated vs non-phosphorylated OPN. We will determine the structural requirements on thrombin for OPN cleavage, and characterize the efficiency of TAFla cleavage of SVVYGLR and other relevant substrates. Aim #2 Cell biology of thrombin cleavage of OPN and its modulation by TAFla We hypothesize that the engagement of the RGD and the SVVYGLR sites on the thrombin-cleaved OPN fragment to RGD-dependent and RGD-independent integrins respectively will lead to different cellular effects. We have generated various GST-OPN fusion proteins that represent the two binding sites either singly or in combination. We will study their effects on Jurkat cells in terms of haptotaxis, metalloprotease secretion, cytokine release, and gene transcription profiles. We will test whether SDF-1alpha TGF-beta1, and the thrombin receptor activation peptide activate alpha4beta1on Jurkat cells. We will test whether thrombin-cleaved OPN induces a prothrombotic phenotype in endothelial cells. Aim #3 The in vivo role of TAFla in mouse inflammation model To test whether TAFla is important in modulating the proinflammatory effect of thrombin-cleaved OPN, we will compare the EAE phenotype in WT and TAFI-null mice and test the OPN-fusion proteins in an OPN-induced peritonitis model. We will confirm that E229K thrombin blockage of BK-induced hypotension is mediated by TAFI activation. We will test the role of TAFla inactivation of C5a in a neutrophil alveolitis model. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENETIC TRANSPORTER
POLYMORPHISMS
HUMAN
NOREPINEPHRINE
Principal Investigator & Institution: Hahn, Maureen K.; Pharmacology; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2002; Project Start 16-NOV-2001; Project End 31-OCT-2002 Summary: The norepinephrine transporter (NET) is responsible for limiting the actions of norepinephrine (NE) in the brain and in the sympathetic nervous system through rapid reuptake of released NE. This proposal attempts to identify mutations in the human NET (hNET) gene that may contribute to cardiovascular and psychiatric disease. DNA samples from patients with orthostatic intolerance and depression will be genotyped for hNET mutations. Genomic DNA will be isolated from blood or tissue samples, and, using primers directed against hNET, polymerase chain reaction and sequence analysis will be performed to determine if polymorphisms exist in coding region of hNET. Mutations that result in amino acid substitutions will be examined for effects on hNET through site-directed mutagenesis of an expression vector containing hNET sequences, transfection and performance of [3H]NE transport assays and protein analysis through Western and radioligand binding assays. Known polymorphisms identified in hypertension will also be examined for their effects on hNET function. Through identification of hNET mutations in diseases affecting noradrenergic function, further understanding of the mechanism of noradrenergic neurotransmission will be achieved and successful therapies for these disorders can be developed that selectively target hNET. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Hypotension
Project Title: GI MECHANISMS
BARRIER
HEAT
INJURY--SYSTEMIC
&
MOLECULAR
Principal Investigator & Institution: Oberley, Larry W.; Professor/Director; Physiology and Biophysics; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2002; Project Start 01-DEC-1998; Project End 30-NOV-2003 Summary: (Adapted from the applicant's abstract): The purpose of this series of studies is to clarify the importance of the gut permeability barrier in the development of heat injury and heat acclimation, and the mechanisms responsible (oxygen free radicals) for damaging the barrier. The authors propose that hyperthermia provokes intestinal ischemia and production of reactive oxygen species (ROS) which decrement barrier function, leading to the exit of LPS from the lumen of the gut into the circulation, in turn, generating cytokines and leading to hypotension. They further propose that heat shock proteins counteract the effect of ROS. They will also determine the location and time course of permeability dysfunction induced by heat. The specific experiments to be carried out address different aspects of the study. 1 Generation of ROS. They will test in vitro (2 strains in cell culture plus a strain transfected with MnSOD, monolayer conductance) and in vivo (51Cr-EDTA clearance, portal vein LPS levels, TNF, and HSP and inducible nitric oxide synthase levels, mannitol permeability) whether membrane function is altered by the elevations in ROS induced by heating, by dietary means and reduced by addition of an antioxidant to the system. 2. HSP protection. Cells expressing elevated HSP will also be tested in the above properties as well as the barrier function of acclimated rats. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HEMODYNAMICS AND OUTCOME IN PEDIATRIC BRAIN INJURY Principal Investigator & Institution: Vavilala, Monica S.; Anesthesiology; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2008 Summary: (provided by applicant): Traumatic brain injury (TBI) is the leading cause of mortality in children over one year of age. Evidence suggests that hypotension after initial brain injury contributes to secondary brain injury and worsens outcome. Altered cerebral physiology including impaired cerebral autoregulation and hyperemia may also contribute to poor outcome following pediatric TBI. Therefore, characterizing optimal cerebral hemodynamics immediately following severe pediatric TBI is important. The objective of the proposed research is to describe the relationship between cerebral hemodynamics following severe pediatric TBI and outcome. The specific aims proposed here will provide new information regarding the early cerebral hemodynamic management of children with severe TBI. The aims are to examine (1) the relationship between cerebral perfusion pressure and outcome, (2) the relationship between persistent impairment of cerebral autoregulation and outcome, and (3) the age-related incidence of hyperemia. The investigators will also examine the relationship between hyperemia and impaired cerebral autoregulation and the relationship between persistent hyperemia and outcome following severe pediatric TBI. It is important to conduct these studies in children of various ages because (1) cerebral hemodynamics change significantly during development, (2) optimal cerebral hemodynamics following severe TBI may differ in young children compared to older children, (3) there is a paucity of physiologic data in children, and (4) pediatric practice is currently extrapolated from adult practice. The results and experience gained in this research will aid in the future study of cerebral hemodynamics in children at risk of cerebral ischemia
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both with and without TBI. The proposed research will be carried out at the University of Washington, well-known known for mentored patient-oriented research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HISTOPATHOLOGY CBF AND NMR ASSESSMENT OF STROKE Principal Investigator & Institution: Helpern, Joseph A.; Professor of Radiology, Psychiatry and p; Nathan S. Kline Institute for Psych Res Psychiatric Research Orangeburg, Ny 10962 Timing: Fiscal Year 2001; Project Start 22-SEP-1993; Project End 31-MAY-2004 Summary: (Verbatim from the Applicant's Abstract) The main goal of this proposal is to investigate to what extent hemodynamic factors are involved in increased tissue damage associated with ischemia under conditions of hyperglycemia. Elevated systemic blood glucose concentrations have been implicated in poor neurological outcome following stroke in experimental animals and humans. Some studies have reported changes in cerebral blood flow (CBF) associated with hyperglycemia and loss of CBF autoregulation has been implicated as a possible complicating factor in poor outcome associated with hyperglycemia in cerebrovascular disease. We have developed a new high-speed MRI technique to monitor CBF continuously and have generated preliminary data which indicate that in rat brain there is an acute increase in CBF with D-glucose infusion with an associated transient loss of autoregulation. These data suggest that impaired hemodynamics may contribute to poor neurological outcome associated with hyperglycemia stroke. This work will improve our understanding of the role of hyperglycemia in stroke and may help lead to new approaches for stroke management. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: HOMEOSTATIC ORIGINS OF MOTIVATION Principal Investigator & Institution: Stricker, Edward M.; Neuroscience; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 01-JUN-1979; Project End 30-JUN-2006 Summary: (provided by applicant): This is a competing renewal application for grant support of research whose general goal is to understand the biological bases of motivated behavior, especially thirst, salt appetite, hunger and satiety. Three series of experiments are proposed. Experiment 1 seeks to determine the early postingestive signals that influence thirst and the secretion of vasopressin (VP) and oxytocin (OT) in rats. In pursuit of this aim, we will determine (a) whether water drinking reduces secretion of VP and OT in response to excitatory stimuli other than that provided by an intravenous NaCl load; (b) whether lesions of area postrema and nucleus tractus solitarius (NTS) blunt the rapid effect of water drinking, or of an intragastric NaCl load, on secretion of VP and OT; and (c) whether maintenance of rats on high-salt diet blunts the rapid inhibitory effect of water drinking on VP and OT secretion. Experiment 2 seeks to determine the excitatory stimuli for thirst during arterial hypotension or hypovolemia, and the inhibitory stimulus for thirst during arterial hypertension. In pursuit of this aim, we will determine (a) whether angiotensin II and neural signals from arterial baroreceptors contribute significantly to thirst during hypotension; (b) whether renal afferent nerves contribute significantly to thirst during hypovolemia in rats with NTS lesions; and (c) whether sinoaortic baroreceptors contribute significantly to the inhibitory effect of arterial hypertension on thirst. Experiment 3 seeks to determine the physiological functions of neurohypophyseal OT secretion in rats given NaCl loads or
36
Hypotension
during arterial hypotension. In pursuit of this aim, we will determine (a) whether OT contributes significantly as a natriuretic hormone when rats are maintained on high-salt diet; and (b) whether OT contributes significantly to secretion of renin during arterial hypotension, and thus to mediation of the induced thirst. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IMMUNOLOGIC HYPERSENSITIVITIES
BASIS
OF
COW
MILK
INDUCED
Principal Investigator & Institution: Sampson, Hugh A.; Professor; Pediatrics; Mount Sinai School of Medicine of Nyu of New York University New York, Ny 10029 Timing: Fiscal Year 2002; Project Start 01-AUG-1999; Project End 31-JUL-2003 Summary: Cow mil is one of the major causes of food hypersensitivity in children. Based on 4 prospective studies, 2.5% of infants develop cow milk allergy in the first year of life [100,000 babies/year in the U.S.] Although exclusive breast feeding reduces the incidence of cow milk allergy, 0.5% of infants exclusively breast fed through the first 6 months of life develop cow milk allergy due to cow milk antigen passed in maternal breast milk. Long-term follow-up indicates that about 80% of these infants "outgrow" [become "tolerant"] their milk allergy by 3 years. However, 15% of infants with milkspecific IgE antibodies at 1 year of age remained milk allergic at 10 years of age and 35% were allergic to other foods at the age of 10 years. Cow milk allergy is associated with a broad spectrum of both IgE- and non-IgE-hypersensitivity disorders: IgE-mediated [urticaria, eczema, rhinoconjunctivitis, asthma, colic, vomiting, diarrhea and hypotension; and non-IgE-mediated [milk-induced enterocolitis syndrome, benign eosinophilic proctocolitis, enteropathy syndrome, allergic eosinophilic gastroenteritis, eosinophilic eosophagitis, and gastroesopha-geal reflex]. The immunologic mechanisms responsible for these hypersensitivities, and the subsequent development of tolerance are poorly understood, and will be addressed in this program project. The combined resources of this program project provide a unique opportunity to define the immunologic bases for four common forms of cow milk hypersensitivity. The first project will identify four distinct patient groups with cow milk allergy [both IgE- and non-IgE-mediated] and non-allergic control group, establish the relative allergenicity of cow milk proteins and map allergenic epitopes [B cell and/or T cell] in these four forms of mil hypersensitivity, investigate basic immunologic mechanisms associated with these hypersensitivities and determine the changes that occur when milk allergy is "outgrown". The second project will seek to define whether pathway(s) employed by intestinal epithelial cells [IELs] to handle cow milk proteins differ from those of nonallergens [e.g. tetanus toxoid] and whether IECs from milk allergic patients handle antigen differently compared to normal controls. Since most patients "outgrow" their milk allergy, IEC function will be re-evaluated once clinical tolerance has developed to determine whether antigen processing of cow milk protein changed [normalized], contributing to the loss of hypersensitivity. The third project provides a unique opportunity to address the issue of oral tolerance induction in normal children and those with distinct forms of cow milk hypersensitivity. Finally the fourth project provides an opportunity to dissect basic immunologic mechanisms of IgE-mediated food hypersensitivity not possible in man. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IMPROVED RENAL PRESERVATION Principal Investigator & Institution: Fahy, Gregory M.; Twenty First Century Medicine, Inc. 10844 Edison Ct Rancho Cucamonga, Ca 91730
Studies
37
Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2004 Summary: (provided by applicant): The ultimate aim of the proposed research is to enable a substantial improvement in human kidney preservation prior to transplantation by extending the safe storage time and improving outcomes after any given period of storage. This proposal will build upon existing results indicating that a new renal preservation solution developed at 21st Century Medicine (Renasol) is superior to the industry standard, UW solution, in both canine and leporine renal transplant models. The proposal will explore a combination of Renasol and a specific new formulation of protein factors ("trophic factors") that dramatically improve hypothermic storage of dog kidneys. More information will be obtained on the appropriate concentration of trophic factors using the rabbit renal transplant model. A potentially valuable additive for Renasol that may help protect human kidneys from the effects of agonal hypotension will also be evaluated. Canine renal transplants will also be performed using kidneys preserved by simple cold storage for 4 days with Renasol and with Renasol + trophic factors. In anticipation of clinical application, and resulting stability requirements, tests will be conducted, using both the canine and leporine models, to show Renasol retains its effectiveness after months of prior storage at 4 deg. C. These studies will result in a final formulation that will be taken into human clinical trials in Phase II and marketed in Phase Ill. During the course of the proposed studies, urine samples will be collected on a routine basis and subjected to protein profiling using an in-house proteomics workstation. These observations will determine whether the degree of hypothermic injury observed is correlated with definable relative or absolute changes in urinary protein concentrations. This may provide a new predictive diagnostic marker of renal preservation injury. The ability to preserve kidneys with less damage prior to transplantation will significantly reduce the costs and risks of posttransplant dialysis, reduce rejection episodes, and increase the net organ supply. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: INCIDENCE OF DRUG-INDUCED LIVER INJURY Principal Investigator & Institution: Chan, Kin-Wei A.; Epidemiology; Harvard University (Sch of Public Hlth) Public Health Campus Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): This is a new application of an epidemiology study among five health maintenance organizations (HMOs) to evaluate the incidence of druginduced liver injury that results in hospitalizations and to assess the association between exposure to specific drugs and liver outcomes not attributable to non-drug cause. The proposed study will be based on collaborative research infrastructure that has already been established at the HMO Research Network, which is funded as a Center for Education and Research on Therapeutics by the Agency for Healthcare Research and Quality. Five HMOs in different regions of the U.S. will participate. They are Fallon Community Health Plan in central Massachusetts, Harvard Pilgrim Health Care in Eastern Massachusetts, Kaiser Permanente Colorado in Denver area, Kaiser Permanente Northwest in Oregon, and Lovelace Clinic in New Mexico, with a combined health plan population of more than two million. Automated hospital discharge data from the HMOs will be used to identify all patients hospitalized with acute liver disease in 2001. Medical records of potential cases will be reviewed and the liver disease attributed to pre-defined causes. Cases not clearly attributed to a non-drug cause will be independently reviewed by two hepatologists to determine their severity and etiology. Cases of probably drug-induced acute liver injury, possibly drug-induced acute injury, idiopathic acute liver disease, and those whose liver events did not have enough
38
Hypotension
information to evaluate causality will be described. Population-based incidence of these acute liver events will be calculated, and they will form the case series in a case-control analysis designed to evaluate the strength of association between drug exposure and these liver events. Two control series (hospital controls and health plan controls) will be identified. This proposed study will serve as a long term valuable data source for the study of drug-induced liver injury. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: INHIBITION PHAGOCYTOPHILA
OF
NADPH
OXIDASE
BY
ANAPLASMA
Principal Investigator & Institution: Carlyon, Jason A.; Internal Medicine; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2003; Project Start 15-AUG-2003; Project End 31-JUL-2008 Summary: (provided by applicant): Human granulocytic ehrlichiosis (HGE) is an emerging infection of the blood that results in leukopenia and thrombocytopenia. If left untreated, the disease can manifest itself as severe neutropenia, hypotension, shock, and may potentially be fatal due to myocarditis, pancarditis, or to opportunistic infections resulting from impaired host defense mechanisms. Recent evidence suggests that kidney and pancreas transplant recipients are at risk for contracting HGE. A. phagocytophila, the etiologic agent of HGE, persists within its mammalian host by colonizing neutrophils. Neutrophils are primary effector cells involved in phagocytosing and killing bacterial invaders. This bactericidal activity is partially dependent on the superoxide anion produced by the rapidly activatable, multi-component enzyme, NADPH oxidase. A. phagocytophila, however, utilizes multiple strategies to prevent superoxide anion production. It is established that the bacterium inhibits the mRNA expression of gp91phox, a component of NADPH oxidase. Preliminary data presented here demonstrates that A. phagocytophila also prevents transcription of rac2, the key factor of NADPH oxidase. Aims 1 and 2 seek to define the mechanisms responsible for the inhibition of rac2 transcription. Evidence suggests that, prior to preventing rac2 and gp91phox mRNA expression once inside the host cell, A. phagocytophila initially inhibits activation of preformed NADPH oxidase components during invasion. Activation of Rac2 represents the initial, integral step of NADPH oxidase assembly. Therefore, Aim 3 will investigate whether A. phagocytophila inhibits Rac2 activation during invasion. Collectively, these studies will decipher the complex means by which A. phagocytophila prevents the neutrophil respiratory burst. In addition, these studies will lead to a more thorough understanding of neutrophil biology, specifically he factors that regulate rac2 mRNA expression and NADPH oxidase activation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: LATE-LIFE DEPRESSION MASKED BY LOW SADNESS Principal Investigator & Institution: Francoeur, Richard B.; None; Columbia Univ New York Morningside 1210 Amsterdam Ave, Mc 2205 New York, Ny 10027 Timing: Fiscal Year 2002; Project Start 01-JAN-2002; Project End 31-DEC-2003 Summary: (provided by applicant): Only ten percent of older adults with depression are estimated to receive treatment, in part due to low levels of detection by primary care clinicians. There is a growing body of evidence that depression among older adults may present in atypical ways, involving low levels of dysphoric mood, especially sadness. However, there has been little research to identify correlates or risk factors for these conditions of masked presentation. The compelling need for such research is suggested
Studies
39
by recent findings that subclinical, intermediate-level symptoms of dysphoria which fail to meet DSMIV diagnostic criteria may be an important risk factor for future stroke episodes. The literature provides evidence that certain physiological conditions that occur with advancing age (vascular diseases, hypotension) are associated with three broad categories of "depression with low sadness": vascular depression, depression related to systolic hypotension, and depression related to diastolic hypotension. Psychosocial factors (chronic life stress, social isolation) are believed to influence expression of depressive symptoms, although it appears that the proposed study would be the first to investigate this. The proposed study is based upon a conceptual model of co-occurrence, or comorbidity, of different forms of "depression with low sadness" associated with underlying physiological conditions. The purpose of the proposed study is to investigate the etiology of these masked forms of depression with the aims of: 1) clarifying distinct patterns of items for depressed affect, low positive affect, and other depressive symptoms; and 2) identifying age-related and depression-specific correlates of these different patterns. A methodologically innovative use of latent trait analysis (MIMIC) will involve interactions between multiple covariates to model the endorsement of specific symptoms by well-focused subgroups, while simultaneously adjusting for the level of overall depression. The proposed study is based on secondary analysis of the first wave from the New Haven site of the EPESE community survey. The empirical model will be replicated on targeted sub-samples (i.e., blacks, white females, white males). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: LUPUS COHORT Principal Investigator & Institution: Petri, Michelle A.; Associate Professor; Medicine; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 30-SEP-1996; Project End 31-MAR-2007 Summary: (provided by applicant): The Hopkins Lupus Cohort is an ongoing, prospective study in which SLE patients are followed by protocol, with visits at a minimum of every 3 months, now in its 16th year. The Cohort is racially balanced, with one-half of the members being African-American, and reflects a broad socioeconomic range. The Cohort represents a 15 year investment in the study of SLE outcomes, sponsored by NIH. It has led to a unique, prospective database of demographic, social, clinical and laboratory (routine, serologic, and antiphospholipid antibody) measures. The four major accomplishments of the Cohort during the last funding period were: 1) the determination that serologic markers of disease activity, such as anti-dsDNA, C3, and C4, have limited utility in the prediction of SLE flare; 2) the determination that the cumulative prednisone dose is predictive of coronary artery disease and osteoporosis, whereas high-dose prednisone is predictive of avascular necrosis; 3) the determination that antiphospholipid antibodies are associated with future risk of thrombosis and with atherosclerosis; and 4) the finding that the poor health status of SLE patients is associated with fibromyalgia, whereas fibromyalgia itself correlates highly with neurally-mediated hypotension, a form of autonomic neuropathy. In this revised grant, four new specific aims will be undertaken. First, in the cohort as a whole and in an inception cohort followed since diagnosis, we will determine the relative importance of disease activity versus corticosteroid treatment as a predictor of specific types of organ damage. Second, in a study of 75 patients seen monthly, we will investigate cytokines and platelet-related factors as predictors of disease activity. Third, 250 patients from the inception cohort will have carotid duplex and helical CT (for coronary calcification scores) at baseline and 2 years later to determine associates and predictors of
40
Hypotension
atherosclerosis, including traditional and novel cardiovascular risk factors. Fourth, we will assess, in 100 SLE patients with and 100 without fibromyalgia, the frequency of autonomic neuropathy and the correlation with health status. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MATERNAL ANESTHESIA AND FETAL CEREBRAL OXYGENATION Principal Investigator & Institution: Reynolds, James D.; Anesthesiology; Duke University Durham, Nc 27706 Timing: Fiscal Year 2002; Project Start 15-DEC-2001; Project End 30-NOV-2003 Summary: The goal of this exploratory/developmental grant is to use novel technology to determine and differentiate the effects of maternal general anesthesia to those of regional anesthesia on fetal cerebral oxygenation. Maintaining an adequate supply of oxygen and nutrients to the fetal brain is of primary importance during manipulations of the gravid female. Prevailing medical practice encourages the use of general anesthesia for such procedures as non-obstetric related surgery and emergent cesarean section. However, relatively little is known about the effects of inhalational agents (e.g. isoflurane) upon fetal cerebral oxygen status. By extension, one could propose that regional techniques (e.g. epidermal anesthesia) might have reduced fetal effects because of the localization of anesthetic to the maternal CNS. However, this benefit could be counter-acted by the maternal hypotension and with respect to fetal effects, is the impracticability of measuring oxygen levels. To that end, we are developing a means (near infrared spectroscopy; NIRS) of continually measuring in utero fetal cerebral oxygenation in pregnant sheep. An NIRS device was designed specifically for in utero animal experimentation. Currently, we have validated our NIRS methodology by measuring changes in fetal sheep cerebral oxygenation in response to systemic decreases in oxygen levels produced by umbilical cord occlusion. With the present proposal, we plan to further optimize our technology by applying it to answer a clinically-relevant question: Does maternal anesthesia alter fetal cerebral oxygenation? Completion of this study will yield new information regarding the effects of maternal anesthesia on fetal cerebral oxygenation and well-being. In addition, this research will produce clinically relevant data that will be of significant interest to anesthesiologists, obstetricians, and general surgeons who are presented parturients with fetal or abdominal distress. It is expected that the results of these studies will be used to further develop and refine standards of care for anesthetic use during pregnancy. These results will also validate our NIRS methodology, and will allow us to refine-optimize the technology and to develop the appropriate analysis tools to quantitatively evaluate the resultant NIRS data. Finally, the results will serve as the basis for a long-term outcome study designed to identify the optimal anesthetic parameters to be used during an episode of fetal distress, maternal surgery, and eventually fetal surgery. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MEASURING HEMODYNAMICS
INTRA/EXTRACELLULAR
VOLUME
AND
Principal Investigator & Institution: Montgomery, Leslie D.; Ldm Associates 1764 Emory St San Jose, Ca 95126 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2004 Summary: (provided by applicant): A device capable of noninvasive real-time measurement of intravascular and extravascular fluid volumes and blood flows does not currently exist. Such a device would provide vital information in the treatment of
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diverse pathophysiologic fluid volume and hemodynamic states including, for example, the management of increased intracranial pressure following trauma, the treatment of disequilibrium and hypotension during renal dialysis, the monitoring of hydrational state of premature infants, and the investigation and diagnosis of orthostatic intolerance associated with dysautonomia and space flight. Currently employed methods are either invasive, such as tracer dilution techniques, or bulky and expensive such as MRI technologies, and often do not yield easily used real-time data during physiologic stress. The central objective of this proposal is to perfect and test a bioelectric impedance device capable of measuring blood flows by impedance plethysmography (IPG) and of measuring compartmental fluid volumes by electrical impedance spectrography (EIS). Fixed frequency bioimpedance by IPG has been reliably used to estimate blood flow and intravascular volume shifts. Swept frequency bioimpedance by EIS has been used to estimate intravascular, interstitial and intracellular fluid volumes. We will base the IPG module of the device on the fixed frequency Tetrapolar High Resolution Impedance Monitor (THRIM Model 2994-D) digital impedance plethysmograph that was developed by UFi, Inc. This employs a fixed frequency of 50 KHz and has been extensively benchmarked in animal and human blood flow studies. For EIS operation, 40 different frequencies will be provided, at log intervals, between 3 and 300 KHz. EIS will use a constant current transformer coupled excitation stage in conjunction with a digital demodulation stage to supply both resistive and reactive impedance components. This will be controlled by a microprocessor system connected via an RS-232 serial interface to PC analysis software. The microprocessor control system will store impedance parameters and signal waveform segments prior to supplying the data to the host for on-line real time analysis and display. Host software will use a deconvolution algorithm to obtain parameters for an R-C equivalent circuit used to model the intravascular, interstitial and intracellular fluid spaces. In this first stage of development we will test the device against a Whitney strain gauge system using occlusion cuffs to 1) measure forearm and calf blood flows in order to validate the IPG module; 2) produce controlled increases in interstitial and intravascular volumes by stepwise venous occlusion to validate the EIS module. It is hoped that the instrument may be further validated during statistically significant clinical trials during a Phase II NIH SBIR grant. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MICROVASCULAR ABNORMALITIES IN SEPSIS Principal Investigator & Institution: Hollenberg, Steven M.; Rush University Medical Center Chicago, Il 60612 Timing: Fiscal Year 2002; Project Start 01-MAY-1998; Project End 31-JUL-2002 Summary: Septic shock, the leading cause of death in intensive care units, is characterized by vasodilation with decreased peripheral vascular resistance, which is often refractory to exogenously administered vasopressor agents. The most important determinant of peripheral vascular resistance is the tone of resistance arterioles, and modulation of tone in these arterioles results from a complex interplay of local vasodilators and vasoconstrictors. The mechanisms involved in the refractory vasodilation seen in sepsis have not been fully elucidated. The current proposal would be the first study to investigate microvascular abnormalities in a clinically relevant model of sepsis by testing responses of resistance arterioles to a range of endogenous vasoactive substances. The long-term objective of this project is to elucidate the pathophysiology of the abnormalities in vascular tone seen in patients with septic shock. The underlying hypothesis is that hypotension and abnormal distribution of blood flow in sepsis result from derangements in microvascular responses to endogenous
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vasoactive substances. The specific hypothesis is that responses of resistance arterioles in cremaster muscles of septic rats measured using in vivo videomicroscopy will differ from controls, and that elucidation of the mechanisms of differences in vasopressor responsiveness will aid in our understanding of important pathogenetic pathways and in the development of innovative therapies for septic shock. Specific aims: 1. To test the hypothesis that a general abnormality of microvascular reactivity is present in sepsis by comparing arteriolar responses to endogenous vasopressors in septic and control animals. 2. To evaluate potential effector mechanisms of sepsis-induced vascular hyporesponsiveness by measuring the effects of inhibitors of second messenger pathways. 3. To elucidate interactions between endogenous vasopressors and vasodilators in mediating vascular hyporesponsiveness in sepsis by testing the effects of nitric oxide synthase, cyclooxygenase, and lipoxgenase inhibitors on vasopressorinduced arteriolar constriction in septic animals. 4. To test the hypothesis that overproduction of nitric oxide by cytokine- inducible nitric oxide synthase plays a pivotal role in inducing vascular hyporesponsiveness in sepsis, first by comparing the effects of selective and nonselective nitric oxide synthase inhibitors on vasopressorinduced arteriolar constriction in septic animals, and then by measuring vascular responsiveness in transgenic septic animal deficient in inducible nitric oxide synthase. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOLECULAR BIOLOGY OF NOREPINEPHRINE BIOSYNTHESIS Principal Investigator & Institution: Sabban, Esther L.; Professor; Biochem and Molecular Biology; New York Medical College Valhalla, Ny 10595 Timing: Fiscal Year 2002; Project Start 01-AUG-1990; Project End 31-MAY-2007 Summary: (provided by applicant): Norepinephrine (NE) is a crucial catecholamine neurotransmitter/hormone mediating a wide range of physiological responses. Alterations in NE neurotransmission are associated with several prevalent disorders, including cardiovascular disorders such as hypertension/hypotension, neuropsychiatric disorders, such as depression and in Parkinson's disease. Regulation of the expression of NE-biosynthetic enzymes, tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (DBH), is a key mechanism of regulation of the NE systems. The specific aims of this proposal are: 1.) Determine the kinetics and the persistence of activation of TH and DBH transcription in rat locus coeruleus with different duration or repetitions of immobilization stress. 2.) Examine the dynamics of pathways involved in transcriptional activation of TH and DBH gene expression in locus coeruleus and adrenal medulla with different durations or repetitions of stress. 3.) Identify the induction of de novo synthesis of transient or long-lasting transcription factors in rat adrenal medulla and locus coeruleus associated with regulation of TH and DBH gene expression by exposure to single and repeated immobilization stress. 4.) Begin to characterize the mechanisms by which the above observed stress responsive factors cross-talk to regulate TH and DBH gene expression. Specifically examine the interaction of AP-l factors and Egr1 on the regulation of TH transcription. The results will provide a crucial understanding of the different transcriptional mechanisms of activation of gene expression of catecholamine producing systems in the CNS and the periphery with acute and repeated exposure to stressful situations. These findings will contribute to the development of new strategies to prevent the harmful maladaptive changes in catecholamine neurotransmission, while enhancing its beneficial adaptive aspects Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: NEGATIVE IMPACT OF ALCOHOL ON ANTIHYPERTENSIVE THERAPY Principal Investigator & Institution: Abdel-Rahman, Abdel A.; Distinguished Professor of Pharmacology; Pharmacology; East Carolina University 1000 E 5Th St Greenville, Nc 27858 Timing: Fiscal Year 2002; Project Start 01-SEP-1988; Project End 31-MAY-2005 Summary: (Adapted from the Investigator's Abstract) This proposal extends our previous findings on the altered hemodynamic actions of systemic ethanol in an animal model of human hypertension and its adverse interaction with centrally acting hypotensive drugs. The proposal addresses this important biomedical problem by investigating the central mechanisms implicated in alcohol actions on blood pressure, and its impact on antihypertensive therapy with clonidine and an emerging class of drugs, the imidazoline (I1) receptor agonists (e.g. rilmenidine). The proposal will focus on the actions of ethanol on the neuronal activity of two brainstem areas, the rostral ventrolateral medulla (RVLM) and the nucleus tractus solitarius (NTS), known to play pivotal roles in cardiovascular regulation and in the hypotensive action of centrallyacting drugs. An innovative approach of this application is the blending of integrative cardiovascular biology studies, in vivo electrochemistry, in situ hybridization, and radiotelemetry to address three specific aims. Aim 1 investigates the acute electrochemical (norepinephrine, NE) and cardiovascular actions of ethanol microinjection into the NTS vs. the RVLM of hypertensive and "normotensive" rats. Additionally, it tests the hypothesis that ethanol selectively alters the neuronal signaling triggered by the I1-receptor in the RVLM. The powerful technique that permits real time monitoring of NE electrochemical signal (index of neuronal activity) and microinjections into, the NTS or RVLM of conscious rats will be used. Aim 2 identifies the neuronal substrates in the brainstem implicated in ethanol attenuation of the baroreflex function and in its reversal of I1 mediated hypotension, using c-fos expression as a marker of neuronal activity. Aim 3 utilizes a newly developed model system to investigate the chronic effects of moderate amounts of ethanol on blood pressure, cardiac autonomic function (spectral analysis of heart rate variability) in radiotelemetered hypertensive and normotensive rats. The hypothesis is tested that ethanol reductions in the "2Aadrenergic receptor expression or I1-receptor binding in the brainstem or the inhibition of their function contribute to the chronic actions of ethanol on blood pressure and on clonidine hypotension. The proposed studies will contribute to the understanding of the mechanism(s) of central ethanol actions on cardiovascular neurobiology. The important aspects of the proposal are the utilization of newly developed model systems and two indices of neuronal activity to elucidate the role of the brainstem neurons in ethanol actions. This proposal, which addresses an important scientific problem, is expected to yield significant new information on the central cardiovascular actions of ethanol and on the treatment of hypertension in alcohol using individuals. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: NEURAL REGULATION OF THE FETAL PARAVENTRICULAR NUCLEUS Principal Investigator & Institution: Mcdonald, Thomas J.; Cornell University Ithaca Office of Sponsored Programs Ithaca, Ny 14853 Timing: Fiscal Year 2002; Project Start 01-DEC-2001; Project End 30-NOV-2003 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: NITRIC VASODILATION
OXIDE
IN
POST
EXERCISE
HYPOTENSION
&
Principal Investigator & Institution: Halliwill, John R.; Assistant Professor; Mayo Clinic Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2002; Project Start 01-DEC-2001; Project End 30-NOV-2002 Summary: The long-term goal of this research is to determine the factors that mediate post-exercise hypotension and vasodilation. A single bout of aerobic exercise (e.g., cycling for 1 hour at a moderate level) produces a long-lasting decrease in blood pressure, known as "post-exercise hypotension." It is believed that post-exercise hypotension may play a role in the beneficial anti-hypertensive effects of endurance exercise training. Conversely, exaggerated post-exercise hypotension may result in a detrimental tendency to faint after exercise. Thus, there is a need to further understand what mediates post-exercise hypotension. Currently it is unknown whether the endogenous vasodilator nitric oxide contributes to this phenomenon. The specific goal of this study is to determine the role of the nitric oxide in post-exercise hypotension and vasodilation. The study plan is based on a randomized crossover design used previously to investigate post-exercise hypotension. After a familiarization session and fitness test, subjects will undergo parallel experiments on two separate days. The order of the experiments will be randomized between sham, a 60 min period of seated upright rest: and exercise, a 60 min period of seated upright cycling at 60% of their peak aerobic power. Exercise of this intensity and duration produces a sustained (about 2 hrs) postexercise hypotension. Following both sham and exercise, subjects will receive, in sequence, systemic alpha-adrenergic blockade (phentolamine) and nitric oxide synthase blockade (L-NMMA). Before and after these interventions, systemic and regional hemodynamics will be measured. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PEROXYNITRITE DECOMPOSITION CATALYST: HEMORRHAGIC SHOCK Principal Investigator & Institution: Mabley, Jon G.; Inotek Pharmaceuticals Corporation 100 Cummings Ctr, Ste 419E Beverly, Ma 01915 Timing: Fiscal Year 2002; Project Start 01-MAY-2002; Project End 31-OCT-2003 Summary: This proposal is intended to establish a new therapeutic approach to save the lives of severely injured trauma victims with hemorrhagic shock (HS). In a small proportion of trauma, a fatal outcome is assured due to the irreversible loss of vital functions or massive blood loss. Frequently, however, emergent resuscitation is possible. These victims survive to hospitalization and are able to receive the full benefits of modern intensive care and surgery. In spite of fluid resuscitation and surgery to repair vascular and parenchymal injuries, however, not all treated patients survive HS. The principal impediment to a successful outcome in this population is the development of cardiovascular failure, a condition in which HS results in profound hypotension hypotension refractory to fluid replacement and inotropic support. There is substantial evidence that HS-induced tissue injury is mediated by profound alterations in the biosynthesis of the free radicals nitric oxide and superoxide anion, and their reaction product peroxynitrite, a toxic oxidant. We are developing a novel metalloporphyrin that acts a speroxynitrite decomposition catalyst. Our lead compound, FP15, is dramatically protective in experimental models of ischemia-reperfusion injury. The central objective of this grant proposal is to establish that FP15 improves hemodynamics, metabolic function, end-organ injury, and survival in a rodent model of hemorrhagic shock. We
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will address this objective by characterizing the pharmacodynamic profile of FP15 in a rat model of severe fixed-pressure HS. We will correlate the cardiovascular (heart, rate, blood pressure), metabolic (serum lactate concentration), and survival dose-responses with serum FP15 concentrations, in order to establish a pharmacodynamic profile. The results of the present application will establish the technical merit and feasibility of FP15 as a novel parenteral therapeutic candidate for HS. PROPOSED COMMERCIAL APPLICATIONS: The annual domestic impact of hemorrhagic shock on the health care market is estimated at > $200 million. The worldwide market in hemorrhagic shock (developed countries only) is four times larger. Given the absence of a specific completely effective therapy, Inotek anticipates market acceptance to be achieved rapidly, at high levels of penetration, and with a high-sustained price point ($1000 per patient). Estimated worldwide gross sales revenues after market entry and maturation (ca. 4 years after FDA approval) equal $800 million (annual). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PHARMACOLOGIC MECHANISMS OF FALLS AND SWAY IN ELDERLY Principal Investigator & Institution: Pepper, Ginette A.; Professor, Colby Endowed Chair; None; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-MAY-2003 Summary: (provided by applicant) Drugs are one of the presumed causes of falls in the elderly. Research has not addressed the pharmacologic mechanisms whereby drugs cause falls. Most medicines associated with falls have anticholinergic activity, but other possible mechanisms are sedation and postural hypotension. This is a pilot study t ascertain plausibility of the hypothesis that anticholinergic activity is a pharmacologic mechanism of drug-induced falls. This study also examines the relationship of postural sway (a measure of static balance), dynamic balance, and fear of falling with pharmacologic properties of drugs. The aims of this project are to describe falls associated with medications; estimate the fall risk associated with anticholinergic drugs; ascertain the amount of variance in the dependent variables (postural sway, dynamic balance, and fear of falling) explained by selected predictor variables (anticholinergic dose, sedation, and postural sway); and compare postural sway at peak and trough of anticholinergic activity. The study is a longitudinal descriptive correlational design. After a preliminary study of 10 subjects to refine study procedures, 110 elderly taking drugs associated with fall with be recruited from community locations. Subjects will be assessed on the predictor variables of anticholinergic dosage (in atropine equivalents computed across all drugs), postural hypotension, and sedation (measured by the Mood Rating Scale and the Digit Symbol Substitution Test), as well as on the dependent variables of postural sway (area of the ellipse, sway velocity, and lateral sway measured using biochemical force platform), functional dynamic balance (Berg Balance Scale) and fear of falling (Modified Falls Efficacy Scale). Fall events (falls, near falls) during 12 months and time to first fall event will be ascertained by fall diaries, postcards, and telephone interview. A subsample of 40 patients taking either drugs with anticholinergic properties or taking no drugs with anticholinergic properties will be compared on sway at projected time of peak and trough drug levels. Analysis will include descriptive statistics, logistic regression, content analysis, stepwise multiple regression, and repeated measures ANOVA. Explanation of significance variance in falls or postural sway by anticholinergic dose and increased postural sway at time estimated peak drug levels would indicate anticholinergic activity is a tenable mechanism of drug-induced
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falling in the elderly. If there is anticholinergic dose effect, elderly adults with high fall risk should be prescribed alternative medications with similar therapeutic effects, but smaller impact on falls. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PLASMA HYPERVISCOSITY FOR CARDIOVASCULAR COLLAPSE Principal Investigator & Institution: Tsai, Amy G.; La Jolla Bioengineering Institute 505 Coast Blvd South San Diego, Ca 920374616 Timing: Fiscal Year 2004; Project Start 01-JAN-2004; Project End 31-DEC-2007 Summary: (provided by applicant): The long-term objective of this project is to demonstrate that hypervious fluids are efficacious in the treatment and improved survival from traumatic hemorrhagic shock. It is proposed to develop a treatment for hypovolemic cardiovascular collapse based on the infusion of high viscosity plasma expanders, which provide a novel small-volume resuscitation that recovers microvascular perfusion for extended periods until surgical control of bleeding is possible. The central hypothesis is that in conditions of hypotension, and cardiovascular collapse, high viscosity plasma restores moderate levels of mean arterial blood pressure needed to ensure open capillaries and tissue perfusion. Our data shows that open capillaries are critical to tissue survival, and viscogenic plasma expanders with tailored oncotic pressure properties restore microvascular function and rescue the organism from hypovolemic cardiovascular collapse. In the case of uncontrolled bleeding, these solutions provide limited-volume resuscitation with maximum microvascular perfusion and a gradual increase in blood pressure thereby minimizing re-bleeding, leading to important savings of blood transfusions, providing a new approach for dealing with conditions in which reduced tissue perfusion jeopardizes tissue survival in field conditions. In this project, a microcirculatory assessment in the hamster window preparation will be used with sophisticated and state of the art measurements of macro and microhemodynaimcs, including local pO2 levels, capillary pressure, and nitric oxide release. The properties of a transfusion fluid in terms of viscosity and oncotic properties which best recovers cardiovascular collapse will be identified in a lethal uncontrolled bleeding model. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: POSTNATAL REGULATORY SYSTEM
MATURATION
OF
CARDIOVASCULAR
Principal Investigator & Institution: Sica, Anthony L.; Physiology and Pharmacology; Suny Downstate Medical Center 450 Clarkson Ave New York, Ny 11203 Timing: Fiscal Year 2002; Project Start 01-AUG-1978; Project End 30-NOV-2004 Summary: (Verbatim from the application): The overall goal of this proposal is to provide physiological and anatomical indices of maturation within neural networks involved in cardiorespiratory (CV-RESP) regulation. We shall focus on brainstem circuit neurons that mediate the CV-RESP responses to hypercapnic stress because: (a) this circuit plays an essential role in the maintenance of blood/gas homeostasis and (b) evidence suggesting that maladaptive responses to hypercapnic stimulation may be involved in the pathogenesis of Sudden Infant Death Syndrome (SIDS).The swine model of early development will be used to test the hypothesis that CV-RESP responses to prolonged hypercapnia are: (a) age-related, (b) modulated by peripheral afferent inputs, and (c) mediated by central a2-adrenoceptors. We also hypothesize that the network response to hypercapnia involves area postrema, nucleus tractus solitarii, and their
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synaptic targets within sympathetic (SYMP) control regions of the lateral medullary reticular formation. We shall test our hypothesis that catecholaminergic cell areas of the piglet medulla, previously shown to be activated by (a) CO2 and (b) hypotension, play crucial roles in the coordinated response. Of special significance are a subset of epinephrinergic neurons located in the SYMP premotor region of the rostral ventrolateral medulla. The effects of prolonged hypercapnia on SYMP outflow from at least two different segmental levels will be recorded, simultaneously with phrenic (PHR) activity. lEG expression will be quantitated with respect to age and brain stem sites. Age-related alterations in physiologic and neqronal responses to hypercapnia will be assessed following blockade of central alpha-2 receptors. Peripheral denervation will determine the importance of peripheral afferent inputs versus central effects ofhypercapnia at different ages. The correlation between lEG expression and SYMPPHR outflows should reveal whether age-related changes in CV-RESP brain circuits (suggesting periods of vulnerability), are also observed in SYMP-PHR outflows; thus explaining the absence of a linear pattern of maturation of CV responses with stress. These studies should identify apparent dissociation between level of lEG expression (neuronal activation), SYMP coherence (regulatory outflow) and CV-RESP responses to stress (critical developmental period). The results should help in our understanding of the most vulnerable period in the life of the child and the pathogenesis ('window of opportunity') of SIDS. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PRECLINICAL DEVELOPMENT OF PEG-TNF Principal Investigator & Institution: Bomalaski, John S.; Pharmacologics, Inc. Astecc Facility #a-217 Lexington, Ky 40506
Professor;
Phoenix
Timing: Fiscal Year 2004; Project Start 01-NOV-1999; Project End 31-JAN-2006 Summary: (provided by applicant): Unformulated human tumor necrosis factor( (huTNF() has anti-tumor activity in mice, but there is little difference between the effective and lethal doses. Systemic administration of unformulated huTNFalpha has been tested in humans. All studies indicated the dose limiting toxicity was usually hypotension, the circulating half life was < 20 min and little anti-tumor activity was seen. Recent results from isolated limb perfusions with huTNFalpha for prolonged times indicated this cytokine to have marked anti-tumor activity in humans with melanoma. This suggests huTNFalpha may be therapeutically useful, provided the toxicity and short circulating half-life can be overcome. Formulation of other biologically active cytokines and proteins with polyethylene glycol (PEG) has significantly improved their safety and increases their circulating half-life. Examples include PEG-alpha interferon and PEG-GCSF, which are now approved by the FDA. The Phase 1 SBIR grant application proposed formulating huTNFalpha with PEG to increase its circulating halflife and increase its safety. An optimal formulation of huTNFalpha was found (termed huTNFalpha-SS PEG 20,000 mw). The circulating half-life, safety and efficacy of this formulation have been substantially increased compared with unformulated huTNFalpha in mice. In a Pre IND meeting with the FDA the final preclinical studies were identified and are the focus of this Phase 2 SBIR application. The specific aims are to: 1) produce cGMP huTNFalpha-SS PEG 20,000 mw; 2) finalize its pharmacological characterization; and 3) test the immunogenicity and its safety in animals according to GLP (Good Laboratory Practice). The data from these studies will provide the final information enabling the filing of an IND with the FDA to support human Phase I clinical testing. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PROPHYLAXIS OF ADRENAL INSUFFICIENCY TO PREVENT CLD Principal Investigator & Institution: Watterberg, Kristi L.; Pediatrics; University of New Mexico Albuquerque Controller's Office Albuquerque, Nm 87131 Timing: Fiscal Year 2002; Project Start 20-SEP-2001; Project End 30-JUN-2006 Summary: (provided by applicant): Chronic lung disease (CLD) is a frequent complication of prematurity, resulting in increased health care costs, prolonged hospital stay, frequent rehospitalizations, and compromised growth and development. Early treatment with dexamethasone may decrease CLD; however, this therapy has serious immediate and long-term adverse effects. Lung inflammation is a prominent early finding in the development of CLD. At the same time, many small premature infants show biochemical evidence and clinical signs consistent with adrenal insufficiency in the first week of life. Based on the hypothesis that early adrenal insufficiency results in amplified responses to inflammatory stimuli, and other physiologic disruptions, leading to ongoing lung injury and CLD, a randomized, blinded, placebo-controlled pilot study of 40 extremely low birth weight infants (ELBW, 500-999 g birth weight) was conducted. This study showed that hydrocortisone prophylaxis against adrenal insufficiency during the first two weeks of life resulted in a significant increase in survival without chronic lung disease. No increases in adverse outcomes were noted; however, the pilot study was not powerful enough to rule out a Type II error. Based on that hypothesis and pilot study, this application proposes a multicenter, randomized trial of 712 ELBW births, to further define the benefits and assess the risks of hydrocortisone prophylaxis against adrenal insufficiency in these infants. Primary outcome measures will be (1) benefit: increased survival without CLD at 36 weeks postmenstrual age; (2) risk: no increase in cerebral palsy at 18 22 months adjusted age. Other measures of neurodevelopmental outcome will also be assessed. The sample size will detect a change of 10 percentage points in successful outcome, and in the incidence of specific adverse effects, with a power of 80%. The hydrocortisone dose will be 1mg/kg/day for 12 days (equivalent to <10% of the typical starting dexamethasone dose), then 0.5mg/kg/day for 3 days. Baseline data on mother and infant, daily clinical data for the first 28 days of life, outcome data at 36 weeks postmenstrual age, and outcome data at 18 - 22 months adjusted age will be collected. Cortisol and cytokines (IL-1B, 1L6, and ILS) will be assayed at baseline and at 6 days of life. After therapy, cortisol response to ACTH will be assayed. If this study confirms the benefits seen in the pilot study, it will result in a significant improvement in health care for premature infants, both by introducing a beneficial new therapy, and by avoiding higher dose dexamethasone. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PROSTANOID BIOSYNTHESIS IN SYSTEMIC MASTOCYTOSIS Principal Investigator & Institution: Oates, John A.; Professor and Chairman; Medicine; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2002; Project Start 01-FEB-2001; Project End 31-JAN-2004 Summary: The objective of the proposed research is to examine the biosynthesis of the mast cell mediator, prostaglandin D2, in patients with systemic mastocytosis, and to explore the potential for improvements in the treatment of this disorder. Prostaglandin D2 (PGD2) is the predominant prostaglandin synthesized by the mast cell and this vasodilator contributes to the attacks of hypotension/shock experienced by some patients with systemic mastocytosis. Inhibition of PGD2 biosynthesis with nonselective cyclooxygenase inhibitors (the nonsteroidal anti- inflammatory drugs) has been employed in the treatment of this disorder, but these drugs that block both
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cyclooxygenase-1 and cyclooxygenase-2 cause major gastrointestinal adverse effects. Either or both of the cyclooxygenase isoforms could be responsible for the biosynthesis of PGD2 in the mast cells of these patients. In the proposed studies, the contribution of and cyclooxygenase-2 to the biosynthesis of PGD2 will be examined, utilizing a selective COX-2 inhibitor, rofecoxib, as a pharmacologic probe for COX-2 dependent PGD2 production. This question also will be addressed by examination of the expression of COX- 1 and COX-2 in mast cells present in the bone marrow and skin of patients with systemic mastocytosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: QUANTITATIVE BRAIN OXIMETRY USING MRI Principal Investigator & Institution: Lin, Weili; Associate Professor; Radiology; University of North Carolina Chapel Hill Aob 104 Airport Drive Cb#1350 Chapel Hill, Nc 27599 Timing: Fiscal Year 2002; Project Start 01-FEB-1999; Project End 31-DEC-2004 Summary: In the past, jugular bulb venous oximetry has been used to provide a global overview of the dynamic relationship between brain oxygen delivery and demand in certain acute neurological disorders. However, the invasive nature of this method as well as the lack of regional specificity have limited the scope of its application in clinical practice. It is critical important to be able to accurately assess and quantify the relationships between oxygen supply and oxygen demand on a regional basis, so that the pathophysiology of acute stroke and related disorders can be investigated. In this proposal, we will test the general hypothesis that the oxygen saturation of venous blood within the brain parenchyma can be measured, in absolute terms, using advanced magnetic resonance imaging (MRI) techniques. Specifically, the MR signal intensity changes induced by the presence of deoxyhemoglobin within the cerebral vasculature will be measured using a novel gradient/spin echo sequence. High resolution maps of regional cerebral blood volume (rCBV) will also be measured using a three-dimensional steady state MRI method. Combining information from these two imaging sequences, the oxygen saturation of blood within the brain parenchyma can be estimated. We will first validate the proposed MRI methods by testing their ability to accurately predict the oxygen saturation of blood within the brain parenchyma of the rat under a wide variety of pathophysiologic conditions. The validation process will be carried out using well established physiologic manipulations that produce global changes in cerebral blood oxygen saturation and rCBV. These will include acute hemorrhagic hypotension, hemodilution, alterations of arterial carbon dioxide tension, and hypoxemia. These experimental paradigms lend themselves to direct comparison with the gold standard used throughout the project-the oxygen saturation of jugular venous blood samples. Finally, well characterized rat models of focal ischemic injury will be used to investigate the regional applicability of the proposed methods. The success of this proposal should provide the opportunity to non- invasively measure the oxygen saturation of blood within the brain parenchyma on a regional basis with high spatial resolution. This capability could introduce a widely available means for monitoring the dynamic pathophysiology of altered oxygen delivery, and the brain's response to certain therapeutic interventions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: RAPID ON-SITE CYANIDE ASSAY FOR BLOOD AND SALIVA SAMPLES Principal Investigator & Institution: Goodridge, Carolyn F.; Cc Technology, Inc. Box 3136, 813 S 2Nd St Laramie, Wy 82071 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2004 Summary: (provided by applicant): The specific aim of this project is to develop a rapid test for the detection of cyanide in blood and saliva. Poisoning due to cyanide can occur vary rapidly in less than a few minutes, but current tests require at least 2 -3 hours for results to be reported. In rural communities, blood tests for cyanide are sent out for analysis and often several days pass before levels are reported. The current method is a head-space GC technique that uses a strong acid to liberate hydrogen cyanide from cyanomethemoglobin. This results in the administration of antidotal therapy without conformation of poisoning. The antidote, intravenous sodium nitrite, can in itself cause severe poisoning due to hypotension and complications can be exacerbated by anemia. Our technology centers on the strong affinity of cyanide for gold nanoparticles. We have demonstrated that gold nanoparticles can bind free cyanide in aqueous solutions at levels of less than 10 ppb. Most of our prior work has been with aqueous cyanide and gold nanoparticle suspensions, however, some work with HCN detection has been performed with gold nanoparticle impregnated test strips. For this project, we will examine a test for cyanide in blood or saliva using a test strip and a releasing agent to create free cyanide from a biological sample. An example of a potential releasing agent is a strong such as sulfuric acid. Gas permeable membrane technology will also be tested to prevent mixing of releasing agents with the gold nanoparticles. In addition to the chemistry of gold nanoparticles and release of cyanide from cyanomethemoglobin we will show the feasibility of a low cost spectroscopic measurement system. We will eliminate the large and costly portion of Raman spectrometers that is associated with dispersion of the spectrum and replace it with a very small inexpensive filter system. This new system will be designed for handheld use by first response personnel for onsite analysis. The long-term objective of this project will be to provide emergency personnel with small handheld device to measure concentrations of cyanide in blood or saliva. We are working with a local fire department to ensure that the design and specifications match the needs of first response personnel. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: RBC MASS, ANS INTEGRITY & SYNCOPE SUSCEPTIBILITY IN CFS Principal Investigator & Institution: Hurwitz, Barry E.; Professor; Psychology; University of Miami-Medical Box 248293 Coral Gables, Fl 33124 Timing: Fiscal Year 2002; Project Start 27-SEP-2000; Project End 31-JUL-2004 Summary: The pathogenesis of the chronic fatigue syndrome (CFS) includes severe and debilitating fatigue, orthostatic intolerance, and the disruption of hematological, autonomic, and cardiovascular function. Our preliminary findings suggest that: 1) reduced red blood cell (RBC) mass is a critical hematological marker of CFS; and 2) RBC mass expansion improves orthostatic tolerance and fatigue beyond that ascribed to plasma volume expansion alone. However, the physiologic mechanisms underlying the RBC mass treatment effect and the relationship of such mechanisms to individual differences in treatment response have not been elucidated. This proposed 5-year study will screen 150 CDC-defined CFS men and women and classify them into low and normal RBC mass groups. The CFS subjects (90 of 105 enrolled) will be studied before and after a 3-month intervention in a randomized double-blind, placebo-controlled
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study of pharmacotherapy to expand RBC mass; specifically, two CFS groups with low RBC (RBC-treated and placebo-treated) will be compared to another CFS group with normal RBC mass (standard and usual care). To assess whether the diminished cardiac function, characteristic of CFS orthostatic intolerance, is a consequence of myocardial origin, echocardiographic evaluation of left ventricular structure and function (left ventricular mass and wall thickness, compliance, and contractility) will be performed. In addition, autonomic integrity will be assessed during a standardized battery of tests (supine rest, paced respiration, Valsalva maneuver, lying-to standing, and sustained handgrip); baroreceptor sensitivity and alpha- and beta-adrenoceptor sensitivity will he tested using adrenoceptor pharmacologic challenge (phenylephrine, isoproterenol). To determine orthostatic susceptibility, a 70 head-up tilt (HUT) test combined with betaadrenoceptor infusion at 2 mug/min (and then again at 5 mug/min, if the previous HUT failed to induce orthostatic hypotension) will be performed. We will further examine the treatment effect on exertional fatigue and hemodynamic and autonomic physiologic response to the HUT tests. Finally, the relation between the criterion (orthostatic hypotension susceptibility) and the predictors (hemodynamic, autonomic, cardiac structure/function and baroreceptor, alpha-adrenoceptor and beta-adrenoceptor sensitivities) will be evaluated to determine the extent to which the predictors are mediating the treatment effects on orthostatic hypotension susceptibility. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REACTIONS OF VIT B12 COMPOUNDS & ENZYMES WITH NO AND N2O Principal Investigator & Institution: Birke, Ronald L.; Professor; City College of New York 138Th St and Convent Ave New York, Ny 10031 Timing: Fiscal Year 2003; Project Start 01-FEB-2003; Project End 31-JAN-2007 Summary: Our long-term objectives are to understand the functions of vitamin B 12 compounds in enzymatic reactions and as therapeutic agents in terms of their chemical properties. Some specific goals of this research project are to investigate the interactions of nitrogen oxides, NO and N20, and nitrite anion with vitamin B12 (cobalamin) compounds in vitro in order to understand their effects on enzymatic reactions of methionine synthase, B 12-MS, and their effectiveness for sequestering trauma induced NO in vivo. One hypothesis is that redox reactions of NO and N20 with the Co(II) and Co(I) forms of cobalamin can effect enzyme functioning. Specifically, we plan to study the complexes formed and the redox behavior of systems of NO, N20, and the nitrite anion with various cobalamin compounds in their three cobalt oxidation states using electrochemical measurements, UV-VIS spectroscopy, resonance Raman spectroscopy (RRS), surface enhanced resonance Raman spectroscopy (SERRS), and electron paramagnetic resonance (EPR) spectroscopy. Nitrogen species formed as reaction products will be investigated by gas chromatography-mass spectrometry (GC-MS), We will also study the reductive cleavage mechanism for the activation of methylcobalamin and adenosylcobalamin. Our aim is to measure equilibrium binding constants, redox reaction rates, and electrochemical reduction potentials for cobalamin redox couples and also to determine the structure of NO binding in their nitrosyl complexes. Experiments will also investigate the solvent and pH effects on the equilibrium and kinetic properties of the complexes. In addition, we will investigate the inactivation of pure methionine synthase obtained from a recombinant strain of E. Coil which overproduces the enzyme. We will compare NO and N20 inactivation by various means including deactivation in an electrochemical cell which produces the cob(I)alamin form of the enzyme, analysis of the inactivated enzyme by twodimensional polyacrylamide gel electrophoresis, and
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Hypotension
stopped-flow kinetic measurements of enzyme catalysis in the presence of NO and N20. Additionally, we will correlate our chemical studies with the effect of various cobalamin compounds on NO generated at the surface of endothelium cells in physiological experiments to be done at Ohio University. These results should help in understanding how NO and N20 work in inhibiting B 12-MS function, if NO can act as a regulator for MS-B 12, and how cobalamins can detoxify organisms with elevated levels of NO which cause the condition of hypotension. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REGULATION OF CBF BY ADENOSINE Principal Investigator & Institution: Winn, H Richard.; Professor and Chairman; Neurological Surgery; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2002; Project Start 01-DEC-1983; Project End 31-MAR-2003 Summary: (Adapted from Applicant's Abstract): The overall goal of this proposal is to test the hypothesis that adenosine (ADO) is involved in cerebral blood flow (CBF) regulation. In our initial years, we focused on the characterization of changes in whole brain during ischemia, hypoxia, hypotension and seizures. We subsequently designed studies to evaluate the role of ADO in the brain microcirculation and created an experimental paradigm to allow discrete activation of the sensory cortex by sciatic nerve stimulation (SNS). We then developed approaches to investigate the causal relationship between ADO and CBF. In the present proposal, we will focus on the cellular and molecular mechanisms involved in ADO's regulation of CBF and brain activity in physiologic and pathophysiologic states, as well as factors regulating endogenous ADO concentrations. We will use a comprehensive multidisciplinary approach involving whole animal studies, in vitro and in vivo vessel preparations, freshly dissociated vascular smooth muscle, radio immunoassay and electrophysiologic (patch clamp) techniques. Specific Aims: (1) To define the specific mechanisms and adenosine receptors involved in pial vasodilation during SNS. (2) To test the hypothesis that diffusion and/or conduction mechanisms are involved in pial vasodilation during SNS. (3) To test the hypothesis that glutamate causes pial vasodilation by means of an ADOrelated mechanism. (4) To test the hypothesis that in vascular smooth muscle (VSM), ADO causes vasodilation by either cAMP- or cGMP-mediated signal transduction pathways. We will also determine the ion channels involved. We will compare the responses in cerebral resistance vessels to that in larger conductance vessels (basilar) and non-cerebral vessels (mesenteric). (5) To define the ADO receptor subtypes that mediate the neuroprotective effects of ADO during hyperglycemic ischemia and reperfusion, and to test the hypothesis that alteration in ADO receptor activity will affect not only the degree of tissue injury but also the neurobehavioral outcome. Further investigations of ADO in the brain will define the role of ADO in metabolic regulation of CBF and allow a more rational treatment of stroke. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: REGULATION OF THE HUMAN INOS GENE IN SEPSIS AND TRAUMA Principal Investigator & Institution: Geller, David A.; Surgery; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 01-JUN-1995; Project End 31-MAY-2004
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Summary: Sepsis, trauma, and infection initiate systemic responses regulated by cytokines and other inflammatory mediators. In extreme conditions, this response can progress to multiple organ failure, a major cause of mortality in surgical patients. Advances in our understanding of this syndrome are based on the discovery that the inducible nitric oxide synthase (iNOS) gene is expressed in nearly every organ and tissue during the septic response. While NO synthesis has beneficial effects during acute inflammation, over-production of NO during sepsis can be detrimental with massive vasodilation and hypotension. Chronic expression of iNOS has been implicated in NOmediated cytotoxicity leading to diabetes, arthritis, neurode generative disorders, and certain cancers. Our laboratory has cloned the human iNOS gene from cytokinestimulated human hepatocytes. We then isolated the promoter region of the human iNOS gene and have shown that the cytokine-responsive DNA elements are located upstream from -4.7 kb. Recently we have characterized a novel NF-kappaB enhancer region that regulates iNOS transcription in response to TNFalpha or IL-1beta, and have shown a role for STAT1alpha in mediating IFNgamma induction. We have also identified extracellular signals that down-regulate iNOS expression including p53 tumor suppressor protein, steroids, heat shock, certain growth factors, and NO itself. Since the human iNOS gene is tightly regulated, we hypothesize that several mechanisms are working jointly to control the expression of this gene. We predict that this will include cytokine-stimulated nuclear factors that exert either positive or negative control over transcription, as well as post-transcriptional mechanisms that regulate iNOS mRNA stability and translational efficiency. In this proposal, we will pursue two interrelated specific aims. AIM I: TO DEFINE THE TRANSCRIPTIONAL MECHANISMS AND FUNCTIONAL PROMOTER ELEMENTS RESPONSIBLE FOR INDUCTION AND SUPPRESSION OF THE HUMAN iNOS GENE. Additional promoter regions will be fully sequenced and characterized in transfection experiments. DNA elements will be analyzed that are required for cytokine- responsiveness, with an initial focus on the interactions between NF-kappaB and STAT1alpha. Specific mechanisms for gene suppression by p53, steroids, heat shock, TGF-beta, and NO will be sought. Positive and negative transcription will be identified by gel shifts and in vivo footprinting assays. AIM II. TO DETERMINE THE POST-TRANSCRIPTIONAL MECHANISMS INVOLVED IN REGULATION OF THE HUMAN iNOS GENE. Post-transcriptional changes in mRNA stability or translational efficiency can also regulate gene expression. Cytokines will be tested for effects on human iNOS mRNA stability. Changes in translational efficiency in response to these agents will be measured by pulse-chase experiments. The 3'-untranslated region of the human iNOS gene will be analyzed for elements that mediate these effects. At the completion of our studies, we will have characterized the molecular regulation of the human iNOS gene. The information gained will increase our understanding of the control of iNOS transcription, describe novel mechanisms of cytokine-synergy in signal transduction, and help in designing therapeutic strategies for pathophysiological disease states where cytokine expression is relevant. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FUNCTION
RHEOLOGICAL
DETERMINANTS
OF
MICROVASCULAR
Principal Investigator & Institution: Lipowsky, Herbert H.; Professor & Chair; Bioengineering; Pennsylvania State University-Univ Park 110 Technology Center University Park, Pa 16802 Timing: Fiscal Year 2002; Project Start 01-JAN-1989; Project End 30-NOV-2004
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Summary: The overall goal of this research is to elucidate the role of blood rheology as a determinant of microvascular function in health and disease. To this end, techniques of intravital microscopy will be applied to evaluate the extent to which red blood cell (RBC) deformability and aggregation, and white blood cell (WBC) deformability and adhesion to the endothelium, affect the resistance to blood flow in vessels ranging from the true capillaries, to the arterioles and venules which serve them. Quantitative indices of microvascular function will be derived from direct in situ measurements of hemodynamic variables in exteriorized tissues such as the mesentery, omentum and cremaster muscle. Specific aims are to elucidate the relationship between blood flow and blood coli mechanical properties within individual microvessels, at branch points throughout the microvascular network and regionally throughout the succession of major microvascular divisions. A major emphasis of the research will be to elucidate microvascular function in the low flow state by either mechanical obstruction of the arterial inflow, hemorrhagic hypotension or pharmacological intervention. Specific studies on RBCs will delineate the role of red cell aggregation in the margination of WBCs, regional resistance to blood flow and recovery from prolonged ischemic episodes. Studies on RBC deformability will seek to elucidate the effect of its decrease on the process of capillary recruitment during tissue hypoxia, its effect on regional resistance to flow and on the resistance to flow in single unbranched microvessels. Studies on RBC concentration will aim to elucidate the relationship between average tissue hematocrit, determined by the dynamics of red cell flux through the microvasculature, and the tube hematocrit, obtained by direct measurements in individual microvessels. The role of WBC deformability will be examined as a determinant of WBC adhesion to the endothelium and resistance to flow. Techniques of optical sectioning microscopy will be applied to elucidate the role that irregularities in the microvessel lumen play in affecting the resistance to blood flow. It is anticipated that the results of these studies will provide insight into the role of mechanical and biochemical properties of blood cells in affecting microvascular function and aid development of therapeutic strategies to treat a variety of pathologies such as anemia, polycythemia, the low flow state, shock, inflammation and blood cell disorders, to name a few. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: RIGHT VENTRICULAR DYSFUNCTION AND TREATMENT Principal Investigator & Institution: Semigran, Marc J.; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114
Assistant
Professor;
Timing: Fiscal Year 2002; Project Start 12-APR-1999; Project End 31-MAR-2004 Summary: Heart failure represents the results of a variety of cardiovascular diseases in which the initial insult to the myocardium may either be identifiable, such as a myocardial infarction, or unknown, such as in dilated cardiomyopathy. In either case, the occurrence of injury to the myocardium leads to an inexorable course of myocardial dysfunction. While most previous investigations have concentrated on the abnormalities in left ventricular function, there is evidence that right ventricular (RV) function is a more important determinant of patients symptoms and prognosis. Few therapies currently exist to improve RV performance, as currently used systemic vasodilator therapy can cause hypotension when nonselective pulmonary vasodilators are added to a patient's therapeutic regimen. Nitric oxide (NO) activates vascular smooth muscle cell soluble guanylate cyclase leading to vasodilation. The vasodilator effect of NO is limited in time by its rapid binding to, and inactivation by hemoglobin. In preliminary studies, inhaled NO has been demonstrated to be a selective pulmonary vasodilator which can
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improve cardiac performance and exercise capacity in heart failure patients. The goal of this proposal is to combine type 5 (cGMP- specific) phosphodiesterase inhibiton with inhaled NO to: 1. Assess the acute alterations in right ventricular function, overall cardiac performance and exercise capacity in heart failure patients treated with the combination of inhaled NO and the type 5 phosphodiesterase inhibitor sildenafil. 2. Assess the acute and chronic effects of selective pulmonary vasodilation with inhaled nitric oxide and type 5 phosphodiesterase inhibition on pulmonary artery resistance and morphology in patients with pulmonary hypertension due to pulmonary vascular disease or to left heart failure. 3. Assess the effects of acute and chronic pulmonary vasodilator and the subsequent decrease in wall stress on the activity of proteins which regulate myocyte apoptosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ROLE OF HEME OXYGENASE-1 EXPRESSION IN ENDOTOXIC SHOCK Principal Investigator & Institution: Perrella, Mark A.; Assistant Professor; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 01-JUL-1998; Project End 30-JUN-2007 Summary: (provided by applicant): Endotoxic shock is a disease process caused by a severe underlying infection. If left unchecked, this process may progress to refractory hypotension, multiple organ system failure, and death. Other than the cardiovascular response and its associated hypotension, abnormalities of the renal, hepatic, pulmonary, and hematologic systems are common during endotoxemia. The development of multiple organ failure contributes significantly to morbidity and mortality. In addition, oxygen-derived free radicals contribute to the cellular and tissue injury associated with endotoxin-induced inflammation. Heme oxygenase (HO)-1 is a cytoprotective enzyme that is induced by stimuli associated with oxidative stress. HO-1 degrades heme (a potent oxidant) to generate carbon monoxide (CO, a vasodilatory gas that has antiinflammatory properties), bilirubin (an antioxidant derived from biliverdin), and iron. Due to properties of HO-1 and its products, it is believed that HO-1 may play an important role in protecting cells and tissues in the settings of increased oxidative stress, such as during endotoxemia. Studies from our laboratory using HO-1 null (-/-) mice confirmed this hypothesis by showing that endotoxemia produced increased oxidative stress, end-organ damage, and death in mice lacking HO-1 compared with wild-type mice. This detrimental outcome did not correlate with the blood pressure response, as HO-1-/- mice had a significantly higher systolic blood pressure in the setting of increased mortality. These data led us to hypothesize that the upregulation of HO-1, and its subsequent cytoprotective effects (outweighing the potential vasodiIatory/hypotensive effects), may play an important role in preventing the pathophysiology of endotoxic shock. Thus, the goals of this proposal are 1) to determine whether vascular overexpression of HO-1 may have beneficial consequences in endotoxin-induced tissue injury and death by using a vasculai smooth muscle celltargeted promoter to generate transgenic mice, 2) to elucidate the role of HO-1 in bone marrow-derived inflammatory cells versus parenchymal cells during endotoxin-induced end-organ damage and death, and 3) to further identify DNA sequences (cis-acting elements) and their cognate DNA-binding proteins (trans-acting factors), that in conjunction with the architectural transcription factor HMG-I/Y, are important for regulating HO-1 transcription during an inflammatory stimulus Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ROLE OF PARABRACHIAL 5-HT IN THIRST AND SALT APPETITE Principal Investigator & Institution: Johnson, Alan K.; Associate Professor; Psychology; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2002; Project Start 01-JAN-1997; Project End 30-NOV-2005 Summary: (provided by the applicant): Body fluid homeostasis depends on reflexes which act to modulate the rate of renal water and sodium loss and on ingestive behaviors (i.e., thirst and salt appetite) that correct deficits. Although renal mechanisms can slow fluid loss, the restoration of vascular volume depends on the ingestion of water and solute (e.g., sodium). The maintenance of extra-cellular volume requires that the CNS receives and processes information about the status of body water and sodium. Several visceral sensory systems are known to provide this afferent input but there is only a very limited understanding about how this information is handled by the CNS. The present proposal builds upon our prior studies on the central processing of afferent signals involved in body fluid and cardiovascular homeostasis. Experiments using a rapid-onset model of sodium depletion accompanied by mild hypotension will focus on defining the role of serotonergic and cholecystokinergic mechanisms associated with the lateral parabrachial nucleus (LPBN) that we have implicated in the regulation of extracellular fluid volume. The proposed studies employing functional (behavioral), pharmacological, electrophysiological and neuroanatomical methods are designed to lead to converging experimental findings to increase our understanding of how the brain processes information necessary for maintaining body fluid and cardiovascular homeostasis. Such new information has relevance for the well-being of normal individuals exposed to physiological (exercise) and environmental (heat) challenges and for understanding mechanisms underlying pathological conditions related to fluid balance (e.g., hypertension; congestive heart failure; renal disease). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ROLE OF SEROTONIN IN SYMPATHETIC FUNCTION Principal Investigator & Institution: Scrogin, Karie E.; Pharmacol & Exper Therapeutics; Loyola University Medical Center Lewis Towers, 13Th Fl Chicago, Il 60611 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2007 Summary: Following a critical amount of blood loss, compensatory neural responses that normally help maintain blood pressure suddenly fail, causing vasodilation, profound bradycardia and life-threatening hypotension. The central nervous system mechanisms that mediate this sympatholytic response are unknown. A more comprehensive understanding of such mechanisms could lead to novel treatments for circulatory shock and other disorders with aberrant activation of sympatholytic reflexes such as myocardial infarct of the inferoposterior wall of the heart, exertional syncope associated with aortic stenosis or neurogenic syncope. In vivo models devised to examine these responses have been limited due to the effects of anesthesia on autonomic function. The objective of this proposal is to elucidate the role of hindbrain serotonergic cellular- and receptor mediated mechanisms in the sudden loss of sympathetic activity that accompanies severe blood loss in the conscious rat. Specifically, studies have been designed to identify the source of serotonin and the receptor populations that mediate sympathetic withdrawal during hemorrhage. The proposed experiments involve novel uses of classic physiological models to study the role of discrete hindbrain neuronal and receptor populations in the regulation of sympathetic function in unanesthetized rats. Anatomical studies that combine neuronal tract tracing with immunhistochemical markers of neuronal phenotype and function will be used to determine the source and
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projection site of serotonin involved in sympathetic reflexes. The novel techniques outlined in this proposal will help to determine hindbrain serotonergic cellular and receptor function on sympathetic regulation in general and on hemorrhage responses in particular, a goal which has, until now, been hampered by the confounding influence of anesthesia on hemorrhage responses and serotonergic function. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ROLE OF S-NITROSOHEMOGLOBIN IN SEPSIS Principal Investigator & Institution: Patel, Rakesh P.; Pathology; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2006 Summary: (provided by applicant): Septic shock is a leading cause of mortality in hospitalized patients and is defined as the systemic inflammatory response to infection. This disease is characterized by hypotension and inflammatory damage to organs including the lung and which ultimately leads to multiple organ failure and death. Nitric oxide (NO) has a critical role in this disease with NO produced from iNOS receiving much attention. However, the role of NO in sepsis remains unclear with both detrimental and beneficial roles reported. An important regulator of NO function in the vasculature is Hemoglobin (Hb). Recent insights into the reactions between NO and Hb have shown that in addition to reactions with the heme, NO also interacts with a critical cysteine residue forming S-nitrosohemoglobin (SNOHb). SNOHb can elicit NO dependent effects and has been investigated principally in the context of physiological regulation of blood flow. The potential role of SNOHb in pathology has not been considered however. Recent studies show that SNOHb is elevated during endotoxemia and in this proposal, the novel concept that SNOHb mediates endotoxin induced hypotensive and inflammatory responses, by modulating production of different redox congeners of NO is put forward. The biological role of redox derivatives of NO, including nitroxyl anion (N0-) in disease remains largely unexplored although functions in promoting vasodilatation and stimulation of inflammatory responses have been suggested. Preliminary data presented herein suggest that SNOHb dependent vasorelaxation occurs via formation of N0- and vasorelaxing effects of red blood cells purified from endotoxin treated rats are demonstrated. These observations have led to the hypothesis that systemic hypotension and inflammation observed in sepsis are mediated by SNOHb. This hypothesis will be tested by pursuit of the following specific aims: 1) Determine the mechanism of SNOHb formation in endotoxic shock; 2) Determine the vasodilatory mechanisms of SNOHb; and 3) Investigate the role of SNOHb as a mediator of inflammatory damage in the lung. Accomplishment of these aims will yield novel insights into both the molecular mechanisms by which NO impacts upon the pathogenesis of septicemia and on possible therapeutic strategies to treat this inflammatory disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SECONDARY BRAIN INJURY IN INTRACEREBRAL HEMORRHAGE Principal Investigator & Institution: Hemphill, Jesse C.; Neurology; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2002; Project Start 15-JUL-2001; Project End 30-JUN-2006 Summary: (provided by applicant): Acute primary non-traumatic intracerebral hemorrhage (ICH) is a common disorder for which there is currently no therapy of proven benefit in improving mortality and functional outcome. In fact, there remains
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controversy regarding the mechanisms by which ICH creates primary and secondary brain injury. The overall objective of this proposal is to produce a program which combines didactic teaching, mentoring, and clinical research to build upon Dr. Hemphill's training in neurologic critical care, thereby allowing him to develop into an independent clinical investigator studying mechanisms of injury and treatment of ICH. While management decisions in ischemic stroke, head trauma, and subarachnoid hemorrhage may be made based on clinical and diagnostic monitoring for secondary brain injury, the usefulness of this in ICH is not known. The overall hypothesis for this project is that secondary brain injury adversely effects outcome after ICH and that approaches that decrease secondary brain injury after ICH will improve outcome. This will be investigated through a series of studies related to clinical, neuromonitoring, and neuroimaging evaluation of secondary brain injury in ICH, culminating in a pilot clinical trial of ICH treatment. Studies will address: 1) the impact of clinical secondary brain insults (systemic hypoxia, hypotension, fever, and seizures) on outcome, 2) the influence of brain tissue hypoxia (measured through direct monitoring of brain tissue oxygen tension in the neurologic intensive care unit) on outcome, 3) the correlation between brain tissue hypoxia and ischemia on dynamic CT perfusion and MR diffusionweighted imaging, and 4) the feasibility of targeting secondary brain injury in a pilot study of ICH treatment. This research should provide new and important information about the role of secondary brain injury in ICH. In conjunction with the didactic training and mentoring undertaken, this program will foster Dr. Hemphill's development into an independent researcher in neurologic critical care, specifically focusing on intracerebral hemorrhage. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SKIN COOLING TO IMPROVE ORTHOSTATIC TOLERANCE Principal Investigator & Institution: Crandall, Craig G.; Associate Professor; Internal Medicine; University of Texas Sw Med Ctr/Dallas Dallas, Tx 753909105 Timing: Fiscal Year 2002; Project Start 01-JAN-2002; Project End 31-DEC-2005 Summary: (provided by applicant): Post-space flight orthostatic hypotension/intolerance occurs in 25 to 66 percent of crew members upon returning to a 1 G environment. The mechanism(s) causing this response are not completely understood. Identification of countermeasures to reduce the incidence of orthostatic intolerance associated with space flight is paramount to NASA's mission. One such countermeasure may be skin surface cooling. In light of this, three specific objectives will be accomplished by the proposal work: 1) Identify an optimal skin surface cooling paradigm that causes the largest increase in autonomic responses (i.e. stroke volume, blood pressure, sympathetic nerve activity, etc.) without causing shivering or altering motor function. 2) Identify the mechanisms by which skin surface cooling increases the aforementioned autonomic responses resulting in improved tolerance to orthostatic stress. 3) Identify whether skin surface cooling is an effective countermeasure to improve orthostatic tolerance in men and women following simulated microgravity exposure using the head-down tilt bed rest model. Upon completion of the proposed studies important information will be provided that will be beneficial for both operational and safety concerns for astronauts, as well as to individuals who suffer from idiopathic orthostatic intolerance. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SPINAL MECHANISMS OF GUSTATORY INDUCED ANALGESIA Principal Investigator & Institution: Dubner, Ronald N.; Professor and Chair; University of Maryland Balt Prof School Baltimore, Md 21201 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2003 Summary: Persistent pain is a serious problem in premature, newborn and young infants. Although it is now known that neonates and young infants exhibit increased pain sensitivity, the fear that anesthetic agents produce respiratory depression, apnea and hypotension in newborns persists clinically and leads to an insufficient control of pain. Of importance for the future management of pain in newborns is the finding in rat pups and human infants that gustatory and orotactile stimulation access endogenous analgesic systems and lead to pain relieving and calming effects. The purpose of this project is to study the underlying mechanisms of gustatory stimulation-induced analgesia and anti-hyperalgesia. Our major hypotheses is that gustatory stimulationinduced analgesia and anti-hyperalgesia in rat pups is mediated, in part, via supraspinal descending pathways that modulate hyperexcitability at the level of the spinal dorsal horn. We will use a model of inflammatory hyperalgesia in rats because it mimics the persistent response to tissue injury produced by surgical intervention and traumatic injury in newborn humans. Correlative histochemical, pharmacological, molecular and physiological studies will be performed to determine the CNS mechanisms involved in the gustatory stimuli-produced behavioral analgesia and anti- hyperalgesia. Aim 1 will examine the postnatal time course of the effects of intraoral sucrose on paw withdrawal responses and test the hypothesis that these effects re mediated by brain stem descending pathways. Aim 2 will test the hypothesis that the behavioral analgesic and anti- hyperalgesic effects of intraoral sucrose involved opioid and monoaminergic mechanisms at the level of the spinal cord. Aim 3 will determine that sucrose-induced analgesia and anti-hyperalgesia suppress spinal dorsal horn neuronal activity and that this effect is produced by activation of descending modulatory systems. Aim 4 will determine the differential mechanisms by which intraoral sucrose modulates the response properties of dorsal horn neurons before and after inflammation. Aim 5 will extend the observations in Project #4 and test the hypothesis that gustatory stimulation in the newborn exposed to cutaneous and visceral inflammation projects against the development of altered nocifensive behaviors in the adult. These studies will lead to a better understanding of the development of analgesic mechanisms and will provide new clinical approaches for activating endogenous mechanisms in newborns. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PRODUCTION
STEROIDS
/VASCULAR
REACTIVITY
/NITRIC
Principal Investigator & Institution: Keller-Wood, Maureen Pharmacodynamics; University of Florida Gainesville, Fl 32611
E.;
OXIDE Professor;
Timing: Fiscal Year 2002; Project Start 06-APR-2001; Project End 31-MAR-2004 Summary: (Adapted from applicant's description): The overall goal of these studies is to test the hypothesis that there is an interaction between increased secretion of adrenal corticosteroids and increased secretion of estrogen during pregnancy which is necessary for normal blood pressure control in the peripartal period. Studies in pregnant, hypocorticoid ewes and clinical experience in pregnant women with hypoadrenocorticism suggest that normal blood pressure control in late pregnancy requires increased adrenal secretion. Insufficient supply of cortisol results in rapid and profound hypotension, with increased morbidity and mortality in both mother and
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fetus. The experiments in this proposal will directly test the hypothesis that a decrease in cortisol at a time of increased estrogen results in a greater decrease in vascular reactivity to phenylephrine and that this correlates with increased production of nitric oxide production in one or more sites in the body. Four groups of ewes will be studied: adrenalectomized, ovariectomized ewes, adrenalectomized ovariectomized ewes treated with estradiol, adrenal- intact ovariectomized ewes, and adrenal-intact ovariectomized ewes treated with estradiol. All adrenalectomized ewes will be treated with aldosterone and cortisol for one week following surgery, and then the adrenal steroid infusions will be stopped to produce the hypoadrenal state. Animals will be studied at a time point (8 hours) in which the adrenalectomized estrogen treated animals are hypotensive, but the adrenalectomized ewes without estradiol treatment are not overtly hypotensive. Experiments will test vascular reactivity in response to phenylephrine in all 4 groups of ewes to test the hypothesis that estrogen administration decreases vascular reactivity in adrenalectomized ewes. Experiments will also determine plasma levels of nitrates and nitrites and the ability of infusion of L-NAME, an inhibitor of nitric oxide synthase (NOS), to increase vascular reactivity in adrenalectomized ewes with estradiol treatment. Experiments will also test the concentrations of cGMP, and levels of iNOS, eNOS, and nNOS protein measured by Western analysis and mRNA by RT-PCR in aorta, uterine artery, mesenteric artery, renal artery, renal interlobular artery, renal medulla and cortex, and skeletal muscle, taken from animals in the same 4 experimental groups. These experiments will determine if absence of cortisol results in increased NOS in one or more of these sites. Samples of tissue will also be examined by immunohistochemistry to more precisely identify the cell populations containing iNOS, eNOS or nNOS in these ewes. These experiments will therefore describe which isoform(s), and in which cells, NOS is altered by cortisol withdrawal, either alone or in combination with increased estrogen. This information will form the basis of future experiments to determine the mechanism of the interaction of estrogen and cortisol in control of NO and regulation of blood pressure during pregnancy. These studies will therefore add to our understanding of normal blood pressure control during pregnancy, and of the pathophysiology of hypoadrenocorticism at term. These studies will also to our understanding of the counterbalancing effects of increased cortisol and increased estrogens in control of normal blood pressure in normal pregnancy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: STRUCTURAL GENOMICS OF NOREPINEPHRINE TRANSPORTERS Principal Investigator & Institution: Blakely, Randy D.; Associate Professor; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2007 Summary: (provided by applicant): The antidepressant-sensitive norepinephrine (NE) transporters (NETs) constitute the major mode of synaptic inactivation of NE. Recent clinical genetic studies by our groups identified a coding mutation, A457P, in one NET allele of a proband with Orthostatic Intolerance (OI) presenting with reduced NE clearance, increased spillover and reduced intraneuronal NE metabolism. The A457P mutation was found to track with measures of postural tachycardia in the proband?s family and to correlate with altered synaptic NE metabolism. In Specific Aim 1, we propose to ascertain the functional impact of the A457P and other identified NET coding mutations in terms of transport and efflux, transporter trafficking and surface expression using heterologous expression systems. Evidence will be sought to support a dominant-negative interaction between mutant and wildtype subunits and whether homomultimeric complexes support NET function. In Specific Aim 2, we propose to
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extend our genetic evaluation of NET deficiency to evaluate additional subjects with OI and cardiomyopathy (CM) using high-throughput gene scanning techniques. These studies will focus on the NET coding exons and splice junctions and also include a recently identified intronic region that plays a critical role in NET gene expression. Methods will be implemented to allow for an evaluation of altered NET protein in biopsies tissue. Finally, attention and mood are dependent on proper noradrenergic signaling in the CNS and symptoms are present in our A457P probands indicating attention deficit, anxiety and hyperarousal. Thus, we propose in Specific Aim 3 to examine NET alleles with primary diagnoses of attention-deficit hyperactivity disorder (ADHD), attentional deficit (ADD) subtype and Major Depression, melancholic subtype, which is characterized by hyperarousal and anxiety. We will select subjects for analysis in both cases on the basis of comorbid tachycardia. Together these studies offer an opportunity for a better understanding of the molecular and behavioral manifestations of genetic NET variation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SYSTEMATIC STUDY OF SELECTIVE SPINAL ANALGESIA IN HUMANS Principal Investigator & Institution: Eisenach, James C.; Professor; Anesthesiology; Wake Forest University Health Sciences Winston-Salem, Nc 27157 Timing: Fiscal Year 2003; Project Start 01-AUG-1992; Project End 30-NOV-2006 Summary: (provided by applicant):Despite an explosion in preclinical research of pain mechanisms and pharmacology, little is known about the utility of non-opioid analgesics in humans or the predictability of animal models of pain or experimental pain in volunteers to the pharmacology of pain treatment in the clinic. This grant performs two functions: to investigate intrathecal injection of novel non-opioid compound for analgesia in humans and to perform neurotoxicity screening to support clinical trials in subsequent cycles. Since 1992, we have introduced clonidine, neostigmine, and adenosine into clinical trails and probed their mechanisms of action and efficacy in animals, volunteers with experimentally induced pain, and patients. In the last cycle we have completed preclinical safety studies of the cyclooxygenase (COX) inhibitor, ketorolac, and are nearly completed with a Phase I safety trial. Preliminary data in rats demonstrate efficacy of intrathecal ketorolac in postoperative pain, and a large upregulation of COX-1 in the spinal cord after surgery. Thus, our first 2 specific aims are: 1. Determine in humans the efficacy of i.t. Ketorolac to treat inflammatory and postoperative pain, and determine ketorolac's CSF pharmacokinetics and dynamics 2. Determine in rats the role of cyclooxygenase isoenzymes and their alteration by AMPA receptor and glial activation in surgery-induced hypersensitivity and its blockade by ketorolac In addition, we have selected as our next target for animal and human testing the clonidine analog, ST9 1. This compound, described over 25 years ago, produces minimal or no hypotension or sedation after intrathecal injection and likely acts at an alpha2-nonA adrenoceptor subtype, which we believe represents the key target for a2 agonists to treat neuropathic pain. Thus, our last specific aim is: 3. Synthesize and perform neurotoxicity testing for ST91 to support IND application These studies will continue the remarkable success of this program to generate novel hypotheses regarding pharmacologic mechanisms and guide preclinical and clinical development in pain treatment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: THE EFFECTS OF HEMODIALYSIS ON THE SLEEP/WAKE CYCLE Principal Investigator & Institution: Parker, Kathy P.; Associate Professor; Adult and Elder Health; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2003; Project Start 01-SEP-1997; Project End 31-DEC-2007 Summary: (provided by applicant): Approximately 50 to 85% of patients with end-stage renal disease on chronic hemodialysis (HD) have sleep complaints and/or sleep disorders-problems that are associated with decreased quality of life and functional health status. Thus, population specific interventions are needed that address both the underlying mechanisms and consequences of these abnormalities. We propose to test a novel application of an existing intervention-cool dialysate (often used to treat hypotension) as opposed to warm dialysate (standard treatment) during HD-for its ability to stabilize the sleep/wake cycle of chronic HD patients. Primary outcome variables include objective measures of nocturnal sleep and daytime sleepiness and selected sleep-related physiological, psychological, behavioral, and general health outcomes. A randomized, single-blinded (investigators) control group, experimental design will be used. Sixty-eight chronic HD patients, age 21 to 70 years, will be recruited and randomized into one of two groups, Group A (experimental) and Group B (control). For individual subjects, the study will (be) conducted over a 9-month period of time and divided into 3 phases-Phase I (3 months), Phase II (3 months), and Phase III (3 months). During Phase I, both groups of subjects will receive standard treatment (warm dialysate) and data regarding nocturnal sleep (objective and subjective measures of sleep latency, sleep efficiency, total sleep time, and sleep disturbance), daytime sleepiness (physiologic, manifest, and introspective), body temperature (distal/proximal skin gradient and axillary body temperature rhythms), psychological (mood), behavioral (daily activity/rest), and general health outcomes (quality of life and functional status) will be collected. During the next 3 months (Phase II), Group A will receive HD with cool dialysate while Group B will continue to receive standard treatment. During Phase III, both study groups will return to baseline treatment and receive HD with warm dialysate. In each Phase, data on all outcomes of interest will be collected. Data analysis will provide important information regarding the impact of this intervention on the sleep/wake cycle of HD patients and other related clinical outcomes. In addition, study results will make a significant contribution to the scientific understanding of how medical treatments may interact with normal systems to induce sleep/wake abnormalities. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: TRIAL OF FLUDROCORTISONE FOR CHRONIC FATIGUE SYNDROME Principal Investigator & Institution: Rowe, Peter C.; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 01-DEC-2001; Project End 30-NOV-2002 Summary: The trial is based on preliminary data showing that upright tilt table testing can provoke a drop in blood pressure consistent with neurally mediated hypotension (NMH) in a high proportion of those with chronic fatigue syndrome (CFS), and that unblinded treatment of the NMH leads to an improvement in CFS symptoms in 40-70% of CFS patients. The specific aim of this study is to determine whether patients aged 18 to 50 years with CFS and NMH will have a greater improvement in (1) self-reported general sense of well being and (2) objective orthostatic tolerance when treated with fludrocortisone than when treated with placebo. Eligible subjects are randomized to
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receive either fludrocortisone (escalating to 0.1 mg/day) or placebo for nine weeks. In week 8-9 of treatment, subjects undergo repeat tilt testing. The primary outcome measure is the proportion with a 15 point improvement in wellness on a 100 point wellness score, and a secondary outcome is the proportion with improvement in the number of minutes before the development of hypotension during upright tilt. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: VESTIBULAR INFLUENCES ON THE SYMPATHETIC NERVOUS SYSTEM Principal Investigator & Institution: Yates, Bill J.; Associate Professor; Otolaryngology; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 01-APR-1990; Project End 31-MAR-2004 Summary: (Adapted from the Investigator's Abstract) Research over the past decade has demonstrated that the vestibular system influences the control of blood pressure, both in humans and in animal models. The effects of the vestibular system on cardiovascular control are mainly mediated through the sympathetic division of the autonomic nervous system. Peripheral vestibular lesions have been shown to diminish the capability to rapidly and accurately make necessary cardiovascular adjustments during changes in posture. Thus, one role of vestibulo-cardiovascular influences appears to be eliciting changes in blood distribution in the body so that stable blood pressure is maintained during movement. However, deficits in correcting blood pressure following vestibular lesions diminish over time, and are less severe when non-labyrinthine sensory cues regarding body position in space are provided; these observations show that pathways that mediate vestibulo-sympathetic reflexes are subject to plasticity. The focus of the current grant is to explore the adaptive plasticity in cardiovascular responses elicited by the central vestibular system. In particular, the role that the cerebellum may play in adaptation of these responses will be examined, as well as the possibility that nonlabyrinthine inputs to the central vestibular system may be important in controlling blood pressure during movement. Three specific aims are proposed in the current application. In the first aim, the role of the posterior cerebellar vermis in modulating vestibulo-cardiovascular responses will be explored. This region of the vestibulocerebellum, which includes the uvula and parts of the nodulus, has been shown in numerous studies to participate in the regulation of blood pressure. Because this cerebellar region has extensive projections to areas of the vestibular nuclei that mediate vestibulo-sympathetic responses and is known to participate in plastic changes in vestibulo-ocular reflexes, it seems likely that the uvula and nodulus modulate vestibular influences on cardiovascular regulation. The second specific aim will determine the sources of non-labyrinthine inputs to the vestibular nuclei, and will explore the role of these signals in modulating activity of vestibular nucleus neurons following vestibular lesions. The third specific aim will determine whether nonlabyrinthine inputs to the vestibular nuclei have the capacity to elicit compensatory blood pressure changes during body rotations. By understanding the mechanisms through which cardiovascular adjustments are made during movement and changes in posture, therapeutic strategies may be developed to alleviate autonomic problems in patients with central or peripheral vestibular lesions and in astronauts, who are known to suffer from postural-related hypotension following spaceflight. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ZINC NEUROTOXICITY IN TRAUMATIC BRAIN INJURY Principal Investigator & Institution: Prough, Donald S.; Chairman; Anesthesiology; University of Texas Medical Br Galveston 301 University Blvd Galveston, Tx 77555 Timing: Fiscal Year 2002; Project Start 15-JUN-2002; Project End 31-MAY-2007 Summary: (provided by applicant): After traumatic brain injury (TBI), systemic hypotension causes secondary ischemic brain injury that markedly worsens mortality and neurologic outcome. We will test the hypothesis that, as a consequence of TBI and posttraumatic hemorrhagic hypotension, neurotoxic concentrations of Zn2+ are released from presynaptic glutamatergic vesicles in association with glutamate, enter postsynaptic neurons through receptor-associated calcium channels (especially AMPA/kainite receptors) and voltage-operated calcium channels, and worsen outcome by accumulating in postsynaptic neurons. Specific aim 1: In rats subjected to TBI with our without hypotension, we will test the hypothesis that neuronal Zn2+ accumulation is related to Zn2+ release, which is proportional to the severity of TBI and hypotension and the interval between TBI and hypotension. Methodologies: microdialysis (Zn2+ and glutamate); staining with the Zn2+-specific dye TSQ (intracellular Zn2+ accumulation); vanadium acid fuchsin (VAF) staining (acute cell injury); staining for DNA fragmentation (TUNEL); ribonuclease protection assays (apoptosis); neuronal counts (histopathologic outcome), and beam walking, beam balance and the Morris water maze (neurobehavioral outcome). Specific aim 2: In rats subjected to moderate TBI with or without hypotension, we will address the hypothesis that after TBI, Zn2+ enters neurons through receptor-associated calcium channels and voltage-operated calcium channels (VOCCs) and that entry through (VOCCs) is enhanced by posttraumatic brain tissue acidosis. Interventions: the NMDA receptor antagonist MK-801, the AMPA/kainite receptor antagonist LY300164, the L-type calcium channel antagonist nimodipine, and increases and decreases in extracellular pH. Methodologies: microdialysis, TSQ staining, and VAF staining. Specific aim 3: In rats subjected to moderate TBI and hypotension, we will address the hypothesis that after, TBI and hypotension, modifying extracellular Zn2+ concentrations will modify neurobehavioral and histopathologic injury. We will test this hypothesis by using intracerebroventricular (icv) injection of Zn2+ and by icv injection of the specific Zn2+-binding apoenzyme of carbonic anhydrase. Methodologies: identical to specific aim 1 plus monitoring for signs of neurologic zinc deficiency. 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 “hypotension” (or synonyms) into the search box. This search gives you access to 3 4
Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.
With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 5 The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print.
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full-text articles. The following is a sample of items found for hypotension in the PubMed Central database: •
Arrest of Endotoxin-Induced Hypotension by Transforming Growth Factor [beta]1. by Perrella MA, Hsieh C, Lee W, Shieh S, Tsai J, Patterson C, Lowenstein CJ, Long NC, Haber E, Shore S, Lee M.; 1996 Mar 5; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=39908
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Endothelial cell-specific knockout of connexin 43 causes hypotension and bradycardia in mice. by Liao Y, Day KH, Damon DN, Duling BR.; 2001 Aug 14; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=55565
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Hypotension and inflammatory cytokine gene expression triggered by factor Xa -nitric oxide signaling. by Papapetropoulos A, Piccardoni P, Cirino G, Bucci M, Sorrentino R, Cicala C, Johnson K, Zachariou V, Sessa WC, Altieri DC.; 1998 Apr 14; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=22560
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Immunization against bacteria- and endotoxin-induced hypotension. by Abdelnoor AM, Johnson AG, Anderson-Imbert A, Nowotny A.; 1981 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=351563
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Interleukin-1 (IL-1) receptor antagonist prevents Staphylococcus epidermidis-induced hypotension and reduces circulating levels of tumor necrosis factor and IL-1 beta in rabbits. by Aiura K, Gelfand JA, Burke JF, Thompson RC, Dinarello CA.; 1993 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=281009
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Modified polyriboinosinic-polyribocytidylic acid complex: induction of serum interferon, fever, and hypotension in rabbits. by Gatmaitan BG, Legaspi RC, Levy HB, Lerner AM.; 1980 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=283725
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Neutralization of bacteria- and endotoxin-induced hypotension by lipoprotein-free human serum. by Abdelnoor AM, Harvie NR, Johnson AG.; 1982 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=347711
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NG-methyl-L-arginine inhibits tumor necrosis factor-induced hypotension: implications for the involvement of nitric oxide. by Kilbourn RG, Gross SS, Jubran A, Adams J, Griffith OW, Levi R, Lodato RF.; 1990 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=53955
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Possible mechanisms of hypotension produced 70% alcoholic extract of Terminalia arjuna (L.) in anaesthetized dogs. by Nammi S, Gudavalli R, Babu BS, Lodagala DS, Boini KM.; 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=270057
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Postural hypotension induced by paroxetine. by Andrews C, Pinner G.; 1998 Feb 21; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=28465
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Unusual hypotension in the ITU. by Guha A.; 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=137265
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The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine.6 The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign references. It is also free to use. If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals. To generate your own bibliography of studies dealing with hypotension, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “hypotension” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for hypotension (hyperlinks lead to article summaries): •
A 62-year-old man with hypotension and an abnormal chest radiograph. Author(s): Chan-Tack KM, Standridge S, Adelstein E. Source: Cleve Clin J Med. 2002 August; 69(8): 632-8. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12184471
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A brief episode of hypotension increases mortality in critically ill trauma patients. Author(s): Zenati MS, Billiar TR, Townsend RN, Peitzman AB, Harbrecht BG. Source: The Journal of Trauma. 2002 August; 53(2): 232-6; Discussion 236-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12169927
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A case with diarrhoea, hypotension, wasting and weight loss. Author(s): Chiam P, Tavintharan S, Poulose V, Fock KM. Source: Journal of Postgraduate Medicine. 2002 October-December; 48(4): 304-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12571390
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A common P-glycoprotein polymorphism is associated with nortriptyline-induced postural hypotension in patients treated for major depression. Author(s): Roberts RL, Joyce PR, Mulder RT, Begg EJ, Kennedy MA. Source: The Pharmacogenomics Journal. 2002; 2(3): 191-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12082591
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A dose-response meta-analysis of prophylactic intravenous ephedrine for the prevention of hypotension during spinal anesthesia for elective cesarean delivery. Author(s): Lee A, Ngan Kee WD, Gin T. Source: Anesthesia and Analgesia. 2004 February; 98(2): 483-90, Table of Contents. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14742392
6 PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.
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A double-blind randomized trial: prophylactic vasopressin reduces hypotension after cardiopulmonary bypass. Author(s): Morales DL, Garrido MJ, Madigan JD, Helman DN, Faber J, Williams MR, Landry DW, Oz MC. Source: The Annals of Thoracic Surgery. 2003 March; 75(3): 926-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12645718
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A nonpeptidyl mimic of superoxide dismutase, M40403, inhibits dose-limiting hypotension associated with interleukin-2 and increases its antitumor effects. Author(s): Samlowski WE, Petersen R, Cuzzocrea S, Macarthur H, Burton D, McGregor JR, Salvemini D. Source: Nature Medicine. 2003 June; 9(6): 750-5. Epub 2003 May 05. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12730689
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A patient with right upper quadrant abdominal pain, hypotension and dyspnoea. Author(s): Wang PW, Kuo PH, Chang YC, Yang PC. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 2002 July; 20(1): 238-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12166574
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Acetylcholinesterase inhibition in the treatment of hypotension. Author(s): Schondorf R. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2003 September; 74(9): 1187. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12933916
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Acetylcholinesterase inhibition: a novel approach in the treatment of neurogenic orthostatic hypotension. Author(s): Singer W, Opfer-Gehrking TL, McPhee BR, Hilz MJ, Bharucha AE, Low PA. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2003 September; 74(9): 1294-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12933939
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Adrenal insufficiency in a patient with severe hypotension caused by bilateral adrenal hemorrhage. Author(s): Runer ER, Brennan JR, Osterman J. Source: Endocrine Practice : Official Journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists. 2002 July-August; 8(4): 30710. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12173919
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Adverse herbal interactions causing hypotension. Author(s): Wong AL, Chan JT, Chan TY. Source: Therapeutic Drug Monitoring. 2003 June; 25(3): 297-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12766556
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Alpha-adrenergic vascular responsiveness during postexercise hypotension in humans. Author(s): Halliwill JR, Dinenno FA, Dietz NM. Source: The Journal of Physiology. 2003 July 1; 550(Pt 1): 279-86. Epub 2003 May 23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12766237
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An unusual cause of respiratory distress and hypotension following removal of a pheochromocytoma. Author(s): Malhotra SK, Ramprabu K, Dutta A, Behera A. Source: Canadian Journal of Anaesthesia = Journal Canadien D'anesthesie. 2002 December; 49(10): 1099-100. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12477689
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Angiographic features of spontaneous intracranial hypotension. Author(s): Koss SA, Ulmer JL, Hacein-Bey L. Source: Ajnr. American Journal of Neuroradiology. 2003 April; 24(4): 704-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12695207
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Another cause of pseudohypotension. Author(s): Wong DH, Hodgson JR. Source: Anesthesia and Analgesia. 2003 June; 96(6): 1838-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12761023
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Answer to case of the month #88. Spontaneous intracranial hypotension. Author(s): Gandhi D, Goyal M, Miller W, Covert S. Source: Canadian Association of Radiologists Journal = Journal L'association Canadienne Des Radiologistes. 2003 April; 54(2): 126-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12736925
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Application of controlled arterial hypotension in endoscopic rhinosurgery. Author(s): Cincikas D, Ivaskevicius J. Source: Medicina (Kaunas, Lithuania). 2003; 39(9): 852-9. English, Lithuanian. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14515047
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Approach to intradialytic hypotension in intensive care unit patients with acute renal failure. Author(s): Doshi M, Murray PT. Source: Artificial Organs. 2003 September; 27(9): 772-80. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12940898
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Arterial catheter pressure cable corrosion leading to artifactual diagnosis of hypotension. Author(s): Skidmore K, Chen J, Litt L. Source: Anesthesia and Analgesia. 2002 November; 95(5): 1192-5, Table of Contents. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12401591
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Arterial hypotension during induction of anesthesia may not be a risk factor for postoperative nausea and vomiting. Author(s): Kranke P, Roewer N, Rusch D, Piper SN. Source: Anesthesia and Analgesia. 2003 January; 96(1): 302-3; Author Reply 303. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12505973
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Arterial hypotension in patients on peritoneal dialysis. Author(s): Passadakis P, Malliara M, Thodis E, Vargemezis V, Oreopoulos DG. Source: Int J Artif Organs. 2002 June; 25(6): 489-95. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12117286
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Asphyxia aggravates systemic hypotension but not pulmonary hypertension in piglets with meconium aspiration. Author(s): Aaltonen M, Soukka H, Halkola L, Jalonen J, Holopainen IE, Kero P, Kaapa PO. Source: Pediatric Research. 2003 March; 53(3): 473-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12595597
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Assessing orthostatic hypotension in older people. Author(s): Reeve PA. Source: Nursing Older People. 2000 October; 12(7): 27-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12008396
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Association between supine hypertension and orthostatic hypotension in autonomic failure. Author(s): Goldstein DS, Pechnik S, Holmes C, Eldadah B, Sharabi Y. Source: Hypertension. 2003 August; 42(2): 136-42. Epub 2003 June 30. Erratum In: Hypertension. 2003 October; 43(4): E12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12835329
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Association between vasovagal hypotension and low sympathetic neural activity during presyncope. Author(s): Cooke WH, Convertino VA. Source: Clinical Autonomic Research : Official Journal of the Clinical Autonomic Research Society. 2002 December; 12(6): 483-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12598954
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Bilateral subdural effusion and cerebral displacement associated with spontaneous intracranial hypotension: diagnostic and management strategies. Report of two cases. Author(s): Hejazi N, Al-Witry M, Witzmann A. Source: Journal of Neurosurgery. 2002 May; 96(5): 956-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12005407
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Biofeedback controlled hemodialysis (BF-HD) reduces symptoms and increases both hemodynamic tolerability and dialysis adequacy in non-hypotension prone stable patients. Author(s): McIntyre CW, Lambie SH, Fluck RJ. Source: Clinical Nephrology. 2003 August; 60(2): 105-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12940612
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Biofeedback regulation of ultrafiltration and dialysate conductivity for the prevention of hypotension during hemodialysis. Author(s): Begin V, Deziel C, Madore F. Source: Asaio Journal (American Society for Artificial Internal Organs : 1992). 2002 MayJune; 48(3): 312-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12059007
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'Blind' epidural blood patch for spontaneous intracranial hypotension. Author(s): Cohen A, Jesuthasan M. Source: Anaesthesia. 2004 February; 59(2): 190-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14725525
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Blood temperature monitor: a novel tool in the management of dialysis-induced hypotension. Author(s): van der Sande FM, Kooman JP, Leunissen KM. Source: Contrib Nephrol. 2002; (137): 245-53. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12101961
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Blood volume controlled hemodialysis in hypotension-prone patients: a randomized, multicenter controlled trial. Author(s): Santoro A, Mancini E, Basile C, Amoroso L, Di Giulio S, Usberti M, Colasanti G, Verzetti G, Rocco A, Imbasciati E, Panzetta G, Bolzani R, Grandi F, Polacchini M. Source: Kidney International. 2002 September; 62(3): 1034-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12164888
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Camphor-Crataegus berry extract combination dose-dependently reduces tilt induced fall in blood pressure in orthostatic hypotension. Author(s): Belz GG, Butzer R, Gaus W, Loew D. Source: Phytomedicine : International Journal of Phytotherapy and Phytopharmacology. 2002 October; 9(7): 581-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12487321
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Can haemodialysis-induced hypotension be predicted? Author(s): Cai Y, Zimmerman A, Ladefoged S, Secher NH. Source: Nephron. 2002; 92(3): 582-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12372941
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CAPD as treatment of chronic debilitating hemodialysis hypotension. Author(s): Merino JL, Rivera M, Teruel JL, Marcen R, Ortuno J. Source: Perit Dial Int. 2002 May-June; 22(3): 429. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12227409
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Cardinal signs of reactions: hypotension following blood transfusion. Author(s): Dzik WH. Source: Vox Sanguinis. 2002 August; 83 Suppl 1: 145-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12617125
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Cerebral angiographic findings of spontaneous intracranial hypotension. Author(s): Roll JD, Larson TC 3rd, Soriano MM. Source: Ajnr. American Journal of Neuroradiology. 2003 April; 24(4): 707-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12695208
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Cerebral hypoperfusion with systemic hypotension during common carotid ligation. Author(s): Watanabe K, Inomata S, Miyabe M, Saito S, Toyooka H. Source: Anaesthesia. 2003 August; 58(8): 819-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12859502
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Cerebrospinal fluid leak demonstrated by three-dimensional computed tomographic myelography in patients with spontaneous intracranial hypotension. Author(s): Fujimaki H, Saito N, Tosaka M, Tanaka Y, Horiguchi K, Sasaki T. Source: Surgical Neurology. 2002 September-October; 58(3-4): 280-4; Discussion 284-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12480244
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Cerebrospinal fluid levels of catechols in patients with neurogenic orthostatic hypotension. Author(s): Goldstein DS, Holmes C, Patronas N, Kopin IJ. Source: Clinical Science (London, England : 1979). 2003 June; 104(6): 649-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12540289
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Characteristics of hypotension-prone haemodialysis patients: is there a critical relative blood volume? Author(s): Barth C, Boer W, Garzoni D, Kuenzi T, Ries W, Schaefer R, Schneditz D, Tsobanelis T, van der Sande F, Wojke R, Schilling H, Passlick-Deetjen J. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 2003 July; 18(7): 1353-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12808173
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Chest pain, hypotension, and bradycardia. Author(s): Hancock EW. Source: Hosp Pract (Off Ed). 1997 December 15; 32(12): 36-8, 41. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12828356
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Chronic hypotension in the dialysis patient. Author(s): Cases A, Coll E. Source: Journal of Nephrology. 2002 July-August; 15(4): 331-5. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12243360
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Chronic mu-opioid receptor stimulation alters cardiovascular regulation in humans: differential effects on muscle sympathetic and heart rate responses to arterial hypotension. Author(s): Kienbaum P, Heuter T, Scherbaum N, Gastpar M, Peters J. Source: Journal of Cardiovascular Pharmacology. 2002 September; 40(3): 363-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12198322
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Clinical application of sodium profiling in the treatment of intradialytic hypotension. Author(s): Coli L, Ursino M, Donati G, Cianciolo G, Soverini ML, Baraldi O, La Manna G, Feliciangeli G, Scolari MP, Stefoni S. Source: Int J Artif Organs. 2003 August; 26(8): 715-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14521168
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Clinical effects of elastic bandage on neurogenic orthostatic hypotension. Author(s): Hasegawa Y, Hakusui S, Hirayama M, Ieda T, Koike Y, Matsuoka Y, Takahashi A. Source: J Gravit Physiol. 2000 July; 7(2): P159-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12697524
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Clinical trial of esmolol-induced controlled hypotension with or without acute normovolemic hemodilution in spinal surgery. Author(s): Lim YJ, Kim CS, Bahk JH, Ham BM, Do SH. Source: Acta Anaesthesiologica Scandinavica. 2003 January; 47(1): 74-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12492801
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Clonidine facilitates controlled hypotension in adolescent children. Author(s): Hackmann T, Friesen M, Allen S, Precious DS. Source: Anesthesia and Analgesia. 2003 April; 96(4): 976-81, Table of Contents. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12651645
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Collapsed superior ophthalmic veins in patients with spontaneous intracranial hypotension. Author(s): Chen WT, Fuh JL, Lirng JF, Lu SR, Wu ZA, Wang SJ. Source: Neurology. 2003 November 11; 61(9): 1265-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14610134
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Combined oral contraceptives do not influence post-exercise hypotension in women. Author(s): Birch K, Cable N, George K. Source: Experimental Physiology. 2002 September; 87(5): 623-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12481937
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Comparison of dialysis and clinical characteristics of patients with frequent and occasional hemodialysis-associated hypotension. Author(s): Tisler A, Akocsi K, Harshegyi I, Varga G, Ferenczi S, Grosz M, Kulcsar I, Locsey L, Samik J, Solt I, Szegedi J, Toth E, Wagner G, Kiss I. Source: Kidney & Blood Pressure Research. 2002; 25(2): 97-102. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12077491
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Congenital predisposition to spontaneous intracranial hypotension: a case report. Author(s): Ontachi Y, Sakajiri K, Higashi S, Yokoyama K, Suzuki M, Asakura H, Nakao S. Source: Headache. 2003 June; 43(6): 678-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12786929
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Connective tissue disorders with spontaneous spinal cerebrospinal fluid leaks and intracranial hypotension: a prospective study. Author(s): Schievink WI, Gordon OK, Tourje J. Source: Neurosurgery. 2004 January; 54(1): 65-70; Discussion 70-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14683542
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Controlled hypotension and minimal inflation pressure: a new approach for pneumatic tourniquet application in upper limb surgery. Author(s): Tuncali B, Karci A, Bacakoglu AK, Tuncali BE, Ekin A. Source: Anesthesia and Analgesia. 2003 November; 97(5): 1529-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14570681
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Controlled hypotension in children: a critical review of available agents. Author(s): Tobias JD. Source: Paediatric Drugs. 2002; 4(7): 439-53. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12083972
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CSF hypovolemia vs intracranial hypotension in “spontaneous intracranial hypotension syndrome”. Author(s): Miyazawa K, Shiga Y, Hasegawa T, Endoh M, Okita N, Higano S, Takahashi S, Itoyama Y. Source: Neurology. 2003 March 25; 60(6): 941-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12654957
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CSF hypovolemia vs intracranial hypotension in “spontaneous intracranial hypotension syndrome”. Author(s): Chung SJ. Source: Neurology. 2003 November 25; 61(10): 1461-2; Author Reply 1462. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14638989
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Decreased bispectral index as an indicator of syncope before hypotension and bradycardia in two patients with needle phobia. Author(s): Win NN, Kohase H, Miyamoto T, Umino M. Source: British Journal of Anaesthesia. 2003 November; 91(5): 749-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14570804
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Defective triple-lumen catheter-an unusual cause of hypotension. Author(s): Neema PK, Sinha PK, Rathod RC. Source: Journal of Cardiothoracic and Vascular Anesthesia. 2003 June; 17(3): 361-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12827589
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Delayed gadolinium enhancement in epidural space of the cervicothoracic spine in a patient with spontaneous intracranial hypotension. Author(s): Hsu HL, Chen CJ, Ro LS, Wang LJ, Wong YC. Source: Chang Gung Med J. 2002 December; 25(12): 854-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12635844
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Diabetic retinopathy with repeated amaurosis fugax caused by orthostatic hypotension. Author(s): Mimura T, Funatsu H, Kitano S, Amano S, Haruyama K, Shimizu E, Araie M, Hori S. Source: American Journal of Ophthalmology. 2003 November; 136(5): 930-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14597053
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Differing incidences of relevant hypotension with combined spinal-epidural anesthesia and spinal anesthesia. Author(s): Klasen J, Junger A, Hartmann B, Benson M, Jost A, Banzhaf A, Kwapisz M, Hempelmann G. Source: Anesthesia and Analgesia. 2003 May; 96(5): 1491-5, Table of Contents. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12707156
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Does orthostatic hypotension predict the occurrence of nocturnal arterial hypertension in the elderly patient? Author(s): Carmona J, Amado P, Vasconcelos N, Almeida L, Santos I, Alves J, Nazare J. Source: Rev Port Cardiol. 2003 May; 22(5): 607-15. English, Portuguese. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12940176
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Does tachycardia correlate with hypotension after trauma? Author(s): Victorino GP, Battistella FD, Wisner DH. Source: Journal of the American College of Surgeons. 2003 May; 196(5): 679-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12742195
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Dose-response related efficacy in orthostatic hypotension of a fixed combination of D-camphor and an extract from fresh crataegus berries and the contribution of the single components. Author(s): Belz GG, Loew D. Source: Phytomedicine : International Journal of Phytotherapy and Phytopharmacology. 2003; 10 Suppl 4: 61-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12807346
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Drug treatment of orthostatic hypotension and vasovagal syncope. Author(s): Frishman WH, Azer V, Sica D. Source: Heart Disease. 2003 January-February; 5(1): 49-64. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12549988
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Dural tear and intracranial hypotension in a chiropractic patient. Author(s): Di Duro JO. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2004 February; 75(2): 3467. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14742632
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Early contingent negative variation of the EEG and attentional flexibility are reduced in hypotension. Author(s): Weisz N, Schandry R, Jacobs AM, Mialet JP, Duschek S. Source: International Journal of Psychophysiology : Official Journal of the International Organization of Psychophysiology. 2002 September; 45(3): 253-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12208532
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Early detection of orthostatic hypotension by quantitative sudomotor axon reflex test (QSART) in type 2 diabetic patients. Author(s): Itoh H, Uebori S, Asai M, Kashiwaya T, Atoh K, Makino I. Source: Intern Med. 2003 July; 42(7): 560-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12879946
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Echocardiographic diagnosis and catheter treatment of hypotension caused by cor triatriatum dexter. Author(s): Bisinov EA, Dieter RS, Ballantyne F 3rd, Wolff MR, Stein JH. Source: Journal of the American Society of Echocardiography : Official Publication of the American Society of Echocardiography. 2003 August; 16(8): 897-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12879002
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Editorial comment--Hypotension after carotid revascularization. Author(s): Dangas G. Source: Stroke; a Journal of Cerebral Circulation. 2003 November; 34(11): 2581-2. Epub 2003 October 30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14593132
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Effect of sertraline hydrochloride on cardiac autonomic dysfunction in patients with hemodialysis-induced hypotension. Author(s): Yalcin AU, Kudaiberdieva G, Sahin G, Gorenek B, Akcar N, Kuskus S, Bayrak F, Timuralp B. Source: Nephron. Physiology [electronic Resource]. 2003 January; 93(1): P21-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12411727
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Effectiveness of intravenous ephedrine infusion during spinal anaesthesia for caesarean section based on maternal hypotension, neonatal acid-base status and lactate levels. Author(s): Turkoz A, Togal T, Gokdeniz R, Toprak HI, Ersoy O. Source: Anaesthesia and Intensive Care. 2002 June; 30(3): 316-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12075638
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Effects of L-threo-3,4-dihydroxyphenylserine on orthostatic hypotension in hemodialysis patients. Author(s): Iida N, Koshikawa S, Akizawa T, Tsubakihara Y, Marumo F, Akiba T, Kawaguchi Y, Imada A, Yamazaki C, Suzuki M. Source: American Journal of Nephrology. 2002 July-August; 22(4): 338-46. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12169865
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Effects of sodium nitroprusside-induced controlled hypotension on pancreatic function assessed by pancreatitis-associated protein in patients undergoing radical prostatectomy. Author(s): Piper SN, Suttner SW, Maleck WH, Kumle B, Haisch G, Boldt J. Source: European Journal of Anaesthesiology. 2002 August; 19(8): 609-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12200953
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Efficacy and safety of midodrine in the treatment of dialysis-associated hypotension. Author(s): Perazella MA. Source: Expert Opinion on Drug Safety. 2003 January; 2(1): 37-47. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12904123
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Efficacy of high sodium intake in a boy with instantaneous orthostatic hypotension. Author(s): Shichiri M, Tanaka H, Takaya R, Tamai H. Source: Clinical Autonomic Research : Official Journal of the Clinical Autonomic Research Society. 2002 February; 12(1): 47-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12102449
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Efficacy of hypertonic saline dextran fluid resuscitation for patients with hypotension from penetrating trauma. Author(s): Wade CE, Grady JJ, Kramer GC. Source: The Journal of Trauma. 2003 May; 54(5 Suppl): S144-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12768117
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Epidural anesthesia, hypotension, and changes in intravascular volume. Author(s): Holte K, Foss NB, Svensen C, Lund C, Madsen JL, Kehlet H. Source: Anesthesiology. 2004 February; 100(2): 281-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14739801
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Epidural blood patch for treatment of spontaneous intracranial hypotension. Author(s): Waguri N, Tomita M, Hayatsu K, Okamoto K, Shimoji K. Source: Acta Anaesthesiologica Scandinavica. 2002 July; 46(6): 747-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12059903
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Epidural granuloma and intracranial hypotension resulting from cervical epidural steroid injection. Author(s): Dietrich CL, Smith CE. Source: Anesthesiology. 2004 February; 100(2): 445-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14739824
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Epinephrine treatment of hypotension in very low birthweight infants. Author(s): Heckmann M, Trotter A, Pohlandt F, Lindner W. Source: Acta Paediatrica (Oslo, Norway : 1992). 2002; 91(5): 566-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12113327
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Eptifibatide-induced acute profound thrombocytopenia presenting as refractory hypotension. Author(s): Rezkalla SH, Hayes JJ, Curtis BR, Aster RH. Source: Catheterization and Cardiovascular Interventions : Official Journal of the Society for Cardiac Angiography & Interventions. 2003 January; 58(1): 76-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12508202
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Erythropoietin, anemia, and orthostatic hypotension: the evidence mounts. Author(s): Rao SV, Stamler JS. Source: Clinical Autonomic Research : Official Journal of the Clinical Autonomic Research Society. 2002 June; 12(3): 141-3. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12269543
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Facticious hypoglycaemia in hypotension. Author(s): MacDuff A, Grant IS. Source: Emergency Medicine Journal : Emj. 2002 July; 19(4): 376. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12101176
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Fasting, halothane, and hypotension. Author(s): Gunter JB. Source: Anesthesia and Analgesia. 2003 May; 96(5): 1537-8; Author Reply 1538. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12707179
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Glycopyrronium and hypotension following combined spinal-epidural anaesthesia. Author(s): Mandal NG. Source: Anaesthesia. 2002 May; 57(5): 513; Author Reply 513-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12004818
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Hand ischemia associated with profound hypotension and radial artery catheterization in a pediatric patient: a case report. Author(s): English LA, Maye JP, Dalton-Link MT. Source: Aana Journal. 2003 February; 71(1): 41-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12776649
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Hypersensitivity to noradrenaline in human omental vein but not artery isolated from a patient with idiopathic orthostatic hypotension. Author(s): Hidestal J, Fredriksen S, Hallen M, Westerdahl J, Thysell H, Bodelsson M. Source: Autonomic Neuroscience : Basic & Clinical. 2002 April 18; 97(1): 55-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12036187
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Hypertension in orthostatic hypotension and autonomic dysfunction. Author(s): Biaggioni I, Robertson RM. Source: Cardiology Clinics. 2002 May; 20(2): 291-301, Vii. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12119802
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Hypotension and bradycardia in infants after the use of topical brimonidine and beta-blockers. Author(s): Mungan NK, Wilson TW, Nischal KK, Koren G, Levin AV. Source: J Aapos. 2003 February; 7(1): 69-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12690374
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Hypotension and cognitive impairment: selective association in patients with heart failure. Author(s): Sabatini T, Barbisoni P, Rozzini R, Trabucchi M. Source: Neurology. 2002 October 8; 59(7): 1118-9; Author Reply 1119. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12370485
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Hypotension and cognitive impairment: selective association in patients with heart failure. Author(s): Sabatini T, Barbisoni P, Rozzini R, Trabucchi M. Source: Neurology. 2002 August 27; 59(4): 651; Author Reply 651. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12196680
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Hypotension as a delayed complication of rupture of a branch of the superior gluteal artery, following buttock contusion. Author(s): Kligman M, Mahrer A, Avi E, Roffman M. Source: Injury. 2002 April; 33(3): 285-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12084654
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Hypotension following combined spinal epidural anaesthesia. Author(s): Davies P, Howells H. Source: Anaesthesia. 2003 September; 58(9): 932; Author Reply 932-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12911396
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Hypotension following combined spinal-epidural anaesthesia for Caesarean section. Left lateral position vs. tilted supine position. Author(s): Mendonca C, Griffiths J, Ateleanu B, Collis RE. Source: Anaesthesia. 2003 May; 58(5): 428-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12693997
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Hypotension in patients on chronic peritoneal dialysis: etiology, management, and outcome. Author(s): Malliara M, Passadakis P, Panagoutsos S, Theodoridis M, Thodis E, Bargman J, Jassal V, Vas S, Vargemezis V, Oreopoulos D. Source: Adv Perit Dial. 2002; 18: 49-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12402586
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Hypotension in the PACU: an algorithmic approach. Author(s): Cowling GE, Haas RE. Source: Journal of Perianesthesia Nursing : Official Journal of the American Society of Perianesthesia Nurses / American Society of Perianesthesia Nurses. 2002 June; 17(3): 159-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12046010
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Hypotension in the very low birthweight infant: the old, the new, and the uncertain. Author(s): Dasgupta SJ, Gill AB. Source: Archives of Disease in Childhood. Fetal and Neonatal Edition. 2003 November; 88(6): F450-4. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14602688
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Hypotension, renal failure, and pulmonary complications in leptospirosis. Author(s): Niwattayakul K, Homvijitkul J, Niwattayakul S, Khow O, Sitprija V. Source: Renal Failure. 2002 May; 24(3): 297-305. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12166696
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Hypothermia does not alter somatosensory evoked potential amplitude and global cerebral oxygen extraction during marked sodium nitroprusside-induced arterial hypotension. Author(s): Kottenberg-Assenmacher E, Armbruster W, Bornfeld N, Peters J. Source: Anesthesiology. 2003 May; 98(5): 1112-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12717132
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Images in cardiovascular medicine. Cyclic tachycardia and hypotension. Author(s): Magnano AR, Bai D, Bloomfield DM. Source: Circulation. 2002 July 2; 106(1): E1-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12093786
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Impairment of cerebral autoregulation in diabetic patients with cardiovascular autonomic neuropathy and orthostatic hypotension. Author(s): Mankovsky BN, Piolot R, Mankovsky OL, Ziegler D. Source: Diabetic Medicine : a Journal of the British Diabetic Association. 2003 February; 20(2): 119-26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12581263
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Incidence and outcome of orthostatic hypotension in stroke patients undergoing rehabilitation. Author(s): Kong KH, Chuo AM. Source: Archives of Physical Medicine and Rehabilitation. 2003 April; 84(4): 559-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12690595
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Incidence and risk factors of asymptomatic first-dose hypotension with angiotensinconverting enzyme inhibitors in chronic heart failure due to systolic dysfunction. Author(s): Thanikachalam S, Manchanda SC. Source: Indian Heart J. 2003 March-April; 55(2): 167-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12921333
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Induced arterial hypotension for interventional thoracic aortic stent-graft placement: impact on intracranial haemodynamics and cognitive function. Author(s): von Knobelsdorff G, Hoppner RM, Tonner PH, Paris A, Nienaber CA, Scholz J, Schulte am Esch J. Source: European Journal of Anaesthesiology. 2003 February; 20(2): 134-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12622498
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Influence of endurance exercise training status and gender on postexercise hypotension. Author(s): Senitko AN, Charkoudian N, Halliwill JR. Source: Journal of Applied Physiology (Bethesda, Md. : 1985). 2002 June; 92(6): 2368-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12015349
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Influences of prostanoids and nitric oxide on post-suspension hypotension in female Sprague-Dawley rats. Author(s): Eatman D, Listhrop RA, Beasley AS, Socci RR, Abukhalaf I, Bayorh MA. Source: Prostaglandins, Leukotrienes, and Essential Fatty Acids. 2003 March; 68(3): 197205. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12591003
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Initial orthostatic hypotension in a 37-year old horse rider. Author(s): Krediet CT. Source: Clinical Autonomic Research : Official Journal of the Clinical Autonomic Research Society. 2002 October; 12(5): 404. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12841175
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Interscalene block-, sedation-, lateral positioning-, and hydralazine-induced hypotension: is it really prudent? Author(s): Sciard D, Matuszczak M, Gebhard R, Kocieniewska D. Source: Anesthesiology. 2002 July; 97(1): 280-1; Author Reply 281. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12131138
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Intracranial hypotension after chiropractic manipulation of the cervical spine. Author(s): Beck J, Raabe A, Seifert V, Dettmann E. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2003 June; 74(6): 821-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12754366
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Intracranial hypotension after intraoperative lumbar cerebrospinal fluid drainage. Author(s): Samadani U, Huang JH, Baranov D, Zager EL, Grady MS. Source: Neurosurgery. 2003 January; 52(1): 148-51; Discussion 151-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12493112
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Intracranial hypotension syndrome due to duropleural fistula after thoracic diskectomy. Author(s): Jahn K, Winkler K, Tiling R, Brandt T. Source: Journal of Neurology. 2001 December; 248(12): 1101-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12013592
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Intracranial hypotension with air bubble on head CT. Author(s): Zvonkina V, Bernardini GL. Source: Neurology. 2002 June 11; 58(11): 1699. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12058110
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Intractable hypotension in septic shock: successful treatment with vasopressin in an infant. Author(s): Leibovitch L, Efrati O, Vardi A, Matok I, Barzilay Z, Paret G. Source: Isr Med Assoc J. 2003 August; 5(8): 596-8. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12929303
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Intradialytic hypotension: an overview of recent, unresolved and overlooked issues. Author(s): Sherman RA. Source: Seminars in Dialysis. 2002 May-June; 15(3): 141-3. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12100450
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Intraindividual reproducibility of postprandial hypotension. Author(s): Puisieux F, Court D, Baheu E, Dipompeo C, Bulckaen H, Dewailly P. Source: Gerontology. 2002 September-October; 48(5): 315-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12169798
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Intrathecal clonidine and severe hypotension after cardiopulmonary bypass. Author(s): Puskas F, Camporesi EM, O'Leary CE, Hauser M, Nasrallah FV. Source: Anesthesia and Analgesia. 2003 November; 97(5): 1251-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14570631
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Intrathecal saline infusion in the treatment of obtundation associated with spontaneous intracranial hypotension: technical case report. Author(s): Binder DK, Dillon WP, Fishman RA, Schmidt MH. Source: Neurosurgery. 2002 September; 51(3): 830-6; Discussion 836-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12188967
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Intravenous calcium in the treatment of postoperative hypotension. Author(s): St John ME, Chandra-Strobos N. Source: Resuscitation. 2002 November; 55(2): 221-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12413762
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Is hypotension a reliable indicator of blood loss from traumatic injury in children? Author(s): Partrick DA, Bensard DD, Janik JS, Karrer FM. Source: American Journal of Surgery. 2002 December; 184(6): 555-9; Discussion 559-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12488166
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Is orthostatic hypotension a consistent finding in the acute geriatric ward? Author(s): Vloet LC, Jansen RW. Source: Archives of Internal Medicine. 2003 May 26; 163(10): 1239-40; Author Reply 1240-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12767967
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Is there an association between maternal hypotension and poor pregnancy outcome?: a review of contemporary literature. Author(s): Warland J, McCutcheon H. Source: Aust J Midwifery. 2002; 15(4): 22-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12593245
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Isolated brain injury as a cause of hypotension in the blunt trauma patient. Author(s): Mahoney EJ, Biffl WL, Harrington DT, Cioffi WG. Source: The Journal of Trauma. 2003 December; 55(6): 1065-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14676652
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Isolated prehospital hypotension after traumatic injuries: a predictor of mortality? Author(s): Shapiro NI, Kociszewski C, Harrison T, Chang Y, Wedel SK, Thomas SH. Source: The Journal of Emergency Medicine. 2003 August; 25(2): 175-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12902005
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Isothermic dialysis for hypotension-prone patients. Author(s): Maggiore Q. Source: Seminars in Dialysis. 2002 May-June; 15(3): 187-90. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12100456
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Lack of effect of percutaneous transluminal renal angioplasty on nocturnal hypotension in renovascular hypertensive patients. Author(s): Ravogli A, Arzilli F, Omboni S, Giovannetti R, Mutti E, Salvetti A, Mancia G. Source: Journal of Hypertension. 1996 January; 14(1): 53-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12013495
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Leptospirosis in northeastern Thailand: hypotension and complications. Author(s): Niwattayakul K, Homvijitkul J, Khow O, Sitprija V. Source: Southeast Asian J Trop Med Public Health. 2002 March; 33(1): 155-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12118444
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Life-threatening hypotension from babesiosis hemolysis. Author(s): Cheng D, Yakobi-Shvlli R, Fernandez J. Source: The American Journal of Emergency Medicine. 2002 July; 20(4): 367. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12098187
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Major pulmonary embolism and shock. Persistent hypotension after thrombolysis treated with improvised mechanical fragmentation of thrombus. Author(s): Lapanun W, Walters DL, McCarthy J, Burstow DJ. Source: The Medical Journal of Australia. 2003 November 3; 179(9): 495-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14583082
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Mean arterial pressure (MAP): an alternative and preferable measurement to systolic blood pressure (SBP) in patients for hypotension detection during hemapheresis. Author(s): Henry JB, Miller MC, Kelly KC, Champney D. Source: Journal of Clinical Apheresis. 2002; 17(2): 55-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12210707
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Mechanisms of hypotension and bradycardia during regional anesthesia in the sitting position. Author(s): Liguori GA, Kahn RL, Gordon MA, Urban MK. Source: Anesthesiology. 2004 January; 100(1): 191-2; Author Reply 192-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14695746
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Methylene blue during cardiopulmonary bypass to treat refractory hypotension in septic endocarditis. Author(s): Grayling M, Deakin CD. Source: The Journal of Thoracic and Cardiovascular Surgery. 2003 February; 125(2): 4267. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12579121
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Midodrine improves chronic hypotension in hemodialysis patients. Author(s): Lin YF, Wang JY, Denq JC, Lin SH. Source: The American Journal of the Medical Sciences. 2003 May; 325(5): 256-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12792244
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Misdiagnosis of spontaneous intracranial hypotension. Author(s): Schievink WI. Source: Archives of Neurology. 2003 December; 60(12): 1713-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14676045
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Mountain rescue--nerve blocks, helicopters, hypothermia and hypotension. Author(s): Craven SA. Source: South African Medical Journal. Suid-Afrikaanse Tydskrif Vir Geneeskunde. 2003 December; 93(12): 879-80, Author Reply 880. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14750478
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Mountain rescue--nerve blocks, helicopters, hypothermia and hypotension. Author(s): Dutkiewicz T, Morgan A. Source: South African Medical Journal. Suid-Afrikaanse Tydskrif Vir Geneeskunde. 2003 December; 93(12): 879. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14750477
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MR findings of spontaneous intracranial hypotension. Author(s): Lin WC, Lirng JF, Fuh JL, Wang SJ, Chang FC, Ho CF, Teng MM, Chang CY. Source: Acta Radiologica (Stockholm, Sweden : 1987). 2002 May; 43(3): 249-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12100320
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Noise-induced compensation for postural hypotension in primary autonomic failure. Author(s): Yamamoto Y, Hidaka I, Iso-o N, Komai A, Soma R, Kwak S. Source: Brain Research. 2002 July 26; 945(1): 71-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12113953
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Nonpostural headache by spontaneous intracranial hypotension. Author(s): Ferrante E, Savino A. Source: Headache. 2003 February; 43(2): 127-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12558767
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Nonsteroidal anti-inflammatory drugs and hypotension among patients hospitalized for invasive Group A streptococcal disease. Author(s): Mulla ZD. Source: Annals of Epidemiology. 2003 August; 13(7): 543-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12932632
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Norepinephrine precursor therapy in neurogenic orthostatic hypotension. Author(s): Kaufmann H, Saadia D, Voustianiouk A, Goldstein DS, Holmes C, Yahr MD, Nardin R, Freeman R. Source: Circulation. 2003 August 12; 108(6): 724-8. Epub 2003 July 28. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12885750
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Occam's razor; anaemia and orthostatic hypotension. Author(s): Gomes ME, Deinum J, Timmers HJ, Lenders JW. Source: Lancet. 2003 October 18; 362(9392): 1282. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14575973
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Orthostatic hypotension and anorexia nervosa: is there a treatment? Author(s): Davani S, Bouhaddi M, Nezelof S, Vandel S, Regnard J, Kantelip JP. Source: Therapie. 2003 March-April; 58(2): 170-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12942861
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Orthostatic hypotension and Holmes-Adie syndrome. Usefulness of the Valsalva ratio in the evaluation of baroreceptor dysfunction. Author(s): Emond D, Lebel M. Source: Journal of Human Hypertension. 2002 September; 16(9): 661-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12214264
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Orthostatic hypotension in acute geriatric ward: is it a consistent finding? Author(s): Weiss A, Grossman E, Beloosesky Y, Grinblat J. Source: Archives of Internal Medicine. 2002 November 11; 162(20): 2369-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12418952
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Orthostatic hypotension in de novo Parkinson disease. Author(s): Bonuccelli U, Lucetti C, Del Dotto P, Ceravolo R, Gambaccini G, Bernardini S, Rossi G, Piaggesi A. Source: Archives of Neurology. 2003 October; 60(10): 1400-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14568810
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Orthostatic hypotension occurs frequently in the first hour after anesthesia. Author(s): Cowie DA, Shoemaker JK, Gelb AW. Source: Anesthesia and Analgesia. 2004 January; 98(1): 40-5, Table of Contents. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14693580
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Orthostatic hypotension predicts mortality. Lessons from the Honolulu Heart Program. Author(s): Schatz IJ. Source: Clinical Autonomic Research : Official Journal of the Clinical Autonomic Research Society. 2002 August; 12(4): 223-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12357271
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Orthostatic hypotension. Author(s): Bradley JG, Davis KA. Source: American Family Physician. 2003 December 15; 68(12): 2393-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14705758
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Orthostatic hypotension. Author(s): Mukai S, Lipsitz LA. Source: Clinics in Geriatric Medicine. 2002 May; 18(2): 253-68. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12180246
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Orthostatic hypotension: causes, classification, and treatment. Author(s): Grubb BP, Kosinski DJ, Kanjwal Y. Source: Pacing and Clinical Electrophysiology : Pace. 2003 April; 26(4 Pt 1): 892-901. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12715851
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Orthostatic tinnitus: an otological presentation of spontaneous intracranial hypotension. Author(s): Arai M, Takada T, Nozue M. Source: Auris, Nasus, Larynx. 2003 February; 30(1): 85-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12589857
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Otoacoustic emissions in patients with hypotension. Author(s): Balatsouras DG, Korres S, Simaskos N, Kandiloros D, Ferekidis E, Economou C. Source: The Journal of Laryngology and Otology. 2003 April; 117(4): 265-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12816214
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Pathophysiology of orthostatic hypotension after bed rest: paradoxical sympathetic withdrawal. Author(s): Kamiya A, Michikami D, Fu Q, Iwase S, Hayano J, Kawada T, Mano T, Sunagawa K. Source: American Journal of Physiology. Heart and Circulatory Physiology. 2003 September; 285(3): H1158-67. Epub 2003 April 24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12714328
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Patients with severe preeclampsia experience less hypotension during spinal anesthesia for elective cesarean delivery than healthy parturients: a prospective cohort comparison. Author(s): Aya AG, Mangin R, Vialles N, Ferrer JM, Robert C, Ripart J, de La Coussaye JE. Source: Anesthesia and Analgesia. 2003 September; 97(3): 867-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12933418
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Perioperative stroke in the brain and spinal cord following an induced hypotension. Author(s): Kim JS, Ko SB, Shin HE, Han SR, Lee KS. Source: Yonsei Medical Journal. 2003 February; 44(1): 143-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12619188
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Plasma levels of catechols and metanephrines in neurogenic orthostatic hypotension. Author(s): Goldstein DS, Holmes C, Sharabi Y, Brentzel S, Eisenhofer G. Source: Neurology. 2003 April 22; 60(8): 1327-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12707437
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Postexercise hypotension differs between white and black women. Author(s): Pescatello LS, Bairos L, Vanheest JL, Maresh CM, Rodriguez NR, Moyna NM, DiPasquale C, Collins V, Meckes CL, Krueger L, Thompson PD. Source: American Heart Journal. 2003 February; 145(2): 364-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12595857
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Postextubation severe bronchospasm and hypotension triggered by exposure to a disinfectant spray. Author(s): Licker M, Spiliopoulos A, Morel D, Chevalley C. Source: Anesthesiology. 2003 September; 99(3): 739-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12960559
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Postprandial hypotension. Author(s): O'Mara G, Lyons D. Source: Clinics in Geriatric Medicine. 2002 May; 18(2): 307-21. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12180250
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Postural hypotension. New insights on pathophysiology and recent treatment advances. Author(s): Freitas J, Loureiro E, Santos R, Carvalho MJ, de Freitas AF. Source: Rev Port Cardiol. 2002 May; 21(5): 597-609. Review. English, Portuguese. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12174522
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Prevalence of orthostatic hypotension among patients presenting with syncope in the ED. Author(s): Sarasin FP, Louis-Simonet M, Carballo D, Slama S, Junod AF, Unger PF. Source: The American Journal of Emergency Medicine. 2002 October; 20(6): 497-501. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12369019
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Preventing hypotension effect of calcium channel blockers. Author(s): Allen R. Source: American Family Physician. 2003 March 1; 67(5): 940; Author Reply 940-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12643354
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Prolonged neurologic complication and MRI abnormalities consequent to intracranial hypotension. Author(s): Eross EJ, Dodick DW. Source: Headache. 2003 April; 43(4): 415. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12656716
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Prolonged refractory hypotension in cardiac surgery after institution of cardiopulmonary bypass. Author(s): Pappalardo F, Landoni G, Franco A, Monaco C, Marino G, Torri G. Source: Journal of Cardiothoracic and Vascular Anesthesia. 2002 August; 16(4): 477-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12154431
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Prophylactic ephedrine prevents hypotension during spinal anesthesia for Cesarean delivery but does not improve neonatal outcome: a quantitative systematic review. Author(s): Lee A, Ngan Kee WD, Gin T. Source: Canadian Journal of Anaesthesia = Journal Canadien D'anesthesie. 2002 JuneJuly; 49(6): 588-99. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12067872
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Pyridoxalated haemoglobin polyoxyethylene conjugate, a nitric oxide scavenger, decreases dose-limiting hypotension associated with interleukin-2 (IL-2) therapy. Author(s): Murakami K, Privalle C, Enkhbaatar P, Shimoda K, Schmalstieg FC, Deangelo J, Lee S, Traber LD, Traber DL. Source: Clinical Science (London, England : 1979). 2003 November; 105(5): 629-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12895141
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Randomized trial of normal saline versus 5% albumin for the treatment of neonatal hypotension. Author(s): Oca MJ, Nelson M, Donn SM. Source: Journal of Perinatology : Official Journal of the California Perinatal Association. 2003 September; 23(6): 473-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=13679934
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Recurrent spontaneous spinal cerebrospinal fluid leaks and intracranial hypotension: a prospective study. Author(s): Schievink WI, Maya MM, Riedinger M. Source: Journal of Neurosurgery. 2003 November; 99(5): 840-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14609162
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Regulation of cerebral blood flow in patients with autonomic dysfunction and severe postural hypotension. Author(s): Hesse B, Mehlsen J, Boesen F, Schmidt JF, Andersen EB, Waldemar G, Andersen AR, Paulson OB, Vorstrup S. Source: Clinical Physiology and Functional Imaging. 2002 July; 22(4): 241-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12402445
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Relative preservation of the renin-angiotensin-aldosterone system response to active orthostatism in type 2 diabetic patients with autonomic neuropathy and postural hypotension. Author(s): Jarmuzewska EA, Ghidoni A, Mangoni AA. Source: Scandinavian Journal of Clinical and Laboratory Investigation. 2003; 63(3): 22532. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12817909
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Reliability of blood pressure measurement for orthostatic hypotension: a hospitalbased questionnaire surve. Author(s): Vilches A, Hyatt RH. Source: Age and Ageing. 2003 May; 32(3): 357. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12720632
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Remifentanil induces consistent and sustained controlled hypotension in children during middle ear surgery. Author(s): Degoute CS, Ray MJ, Gueugniaud PY, Dubreuil C. Source: Canadian Journal of Anaesthesia = Journal Canadien D'anesthesie. 2003 March; 50(3): 270-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12620951
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Risperidone and exaggerated hypotension during a spinal anesthetic. Author(s): Williams JH, Hepner DL. Source: Anesthesia and Analgesia. 2004 January; 98(1): 240-1, Table of Contents. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14693627
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Selegiline in the treatment of Parkinson's disease: its impact on orthostatic hypotension. Author(s): Bhattacharya KF, Nouri S, Olanow CW, Yahr MD, Kaufmann H. Source: Parkinsonism & Related Disorders. 2003 March; 9(4): 221-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12618057
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Sensorimotor anesthesia and hypotension after subarachnoid block: combined spinal-epidural versus single-shot spinal technique. Author(s): Goy RW, Sia AT. Source: Anesthesia and Analgesia. 2004 February; 98(2): 491-6, Table of Contents. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14742393
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Severe hypotension complicating primary angioplasty: allergy to abciximab. Author(s): Hawkins C, Gatenby P, McGill D. Source: Allergy. 2003 July; 58(7): 688-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12823141
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Severe hypotension in the prone position in a child with neurofibromatosis, scoliosis and pectus excavatum presenting for posterior spinal fusion. Author(s): Alexianu D, Skolnick ET, Pinto AC, Ohkawa S, Roye DP Jr, Solowiejczyk DE, Hyman JE, Sun LS. Source: Anesthesia and Analgesia. 2004 February; 98(2): 334-5, Table of Contents. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14742365
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Shy-Drager syndrome and severe unexplained intraoperative hypotension responsive to vasopressin. Author(s): Vallejo R, DeSouza G, Lee J. Source: Anesthesia and Analgesia. 2002 July; 95(1): 50-2, Table of Contents. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12088941
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Solving the problem of spinal-induced hypotension in obstetric anesthesia. Author(s): Macarthur A. Source: Canadian Journal of Anaesthesia = Journal Canadien D'anesthesie. 2002 JuneJuly; 49(6): 536-9. English, French. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12067862
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Spinal anesthesia hypotension in elective cesarean section in parturients wearing extra-strong compression stockings. Author(s): Iwama H, Ohmizo H, Furuta S, Ohmori S, Watanabe K, Kaneko T. Source: Archives of Gynecology and Obstetrics. 2002 December; 267(2): 85-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12439553
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Spinal MR findings in spontaneous intracranial hypotension. Author(s): Chen CJ, Lee TH, Hsu HL, Tseng YC, Wong YC, Wang LJ. Source: Neuroradiology. 2002 December; 44(12): 996-1003. Epub 2002 November 14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12483446
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Spontaneous cervical spine cerebrospinal fluid leak with resultant intracranial hypotension. Author(s): Ong B, Fong W. Source: Clinical Nuclear Medicine. 2003 November; 28(11): 916-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14578709
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Spontaneous intracranial hypotension (SIH): the early appearance of urinary bladder activity in RI cisternography is a pathognomonic sign of SIH? Author(s): Ishihara S, Otani N, Shima K. Source: Acta Neurochir Suppl. 2003; 86: 587-9. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14753511
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Spontaneous intracranial hypotension causing a partial third cranial nerve palsy: a novel observation. Author(s): Warner GT. Source: Cephalalgia : an International Journal of Headache. 2002 December; 22(10): 8223. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12485210
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Spontaneous intracranial hypotension causing confusion and coma: a headache for the neurologist and the neurosurgeon. Author(s): Whiteley W, Al-Shahi R, Myles L, Lueck CJ. Source: British Journal of Neurosurgery. 2003 October; 17(5): 456-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14635752
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Spontaneous intracranial hypotension causing reversible frontotemporal dementia. Author(s): Fishman RA, Dillon WP. Source: Neurology. 2002 September 10; 59(5): 787; Author Reply 787. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12221188
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Spontaneous intracranial hypotension due to thoracic disc herniation. Case report. Author(s): Winter SC, Maartens NF, Anslow P, Teddy PJ. Source: Journal of Neurosurgery. 2002 April; 96(3 Suppl): 343-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11990845
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Spontaneous intracranial hypotension from intradural thoracic disc herniation. Case report. Author(s): Rapport RL, Hillier D, Scearce T, Ferguson C. Source: Journal of Neurosurgery. 2003 April; 98(3 Suppl): 282-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12691385
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Spontaneous intracranial hypotension in the absence of magnetic resonance imaging abnormalities. Author(s): Schoffer KL, Benstead TJ, Grant I. Source: The Canadian Journal of Neurological Sciences. Le Journal Canadien Des Sciences Neurologiques. 2002 August; 29(3): 253-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12195615
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Spontaneous intracranial hypotension resulting in coma. Author(s): Evan RW, Mokri B. Source: Headache. 2002 February; 42(2): 159-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12005297
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Spontaneous intracranial hypotension treated with a cervical epidural blood patch. Author(s): Usui T, Saito S, Goto F. Source: European Journal of Anaesthesiology. 2003 June; 20(6): 500-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12803273
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Spontaneous intracranial hypotension. Author(s): Chung SP, Ha YR, Kim SW, Yoo IS. Source: The American Journal of Emergency Medicine. 2003 November; 21(7): 605-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14655245
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Spontaneous intracranial hypotension. Author(s): Zaatreh M, Finkel A. Source: Southern Medical Journal. 2002 November; 95(11): 1342-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12540006
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Spontaneous intracranial hypotension. Author(s): Kalamangalam GP, Haq N, Ellis SJ. Source: Archives of Neurology. 2002 June; 59(6): 1027. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12056942
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Spontaneous intracranial hypotension: a rare cause of labyrinthine hydrops. Author(s): Portier F, de Minteguiaga C, Racy E, Huy PT, Herman P. Source: The Annals of Otology, Rhinology, and Laryngology. 2002 September; 111(9): 817-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12296337
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Spontaneous intracranial hypotension: quick clinical and magnetic resonance imaging response to corticosteroids. A case report. Author(s): Pascual LF, Santos S, Escalza I, Iniguez C, Morales-Asin F. Source: Headache. 2002 May; 42(5): 359-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12047337
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Subdural haematoma: a potentially serious consequence of spontaneous intracranial hypotension. Author(s): de Noronha RJ, Sharrack B, Hadjivassiliou M, Romanowski CA. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2003 June; 74(6): 752-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12754345
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Successful treatment of severe orthostatic hypotension with erythropoietin. Author(s): Kawakami K, Abe H, Harayama N, Nakashima Y. Source: Pacing and Clinical Electrophysiology : Pace. 2003 January; 26(1 Pt 1): 105-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12685148
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Supratentorial and infratentorial intraparenchymal hemorrhage secondary to intracranial CSF hypotension following spinal surgery. Author(s): Thomas G, Jayaram H, Cudlip S, Powell M. Source: Spine. 2002 September 15; 27(18): E410-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12634578
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Sympathetic nerve activity in hypotension and orthostatic intolerance. Author(s): Mano T, Iwase S. Source: Acta Physiologica Scandinavica. 2003 March; 177(3): 359-65. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12609007
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Techniques for preventing hypotension during spinal anaesthesia for caesarean section. Author(s): Emmett RS, Cyna AM, Andrew M, Simmons SW. Source: Cochrane Database Syst Rev. 2002; (3): Cd002251. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12137652
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Temazepam, but not zolpidem, causes orthostatic hypotension in astronauts after spaceflight. Author(s): Shi SJ, Garcia KM, Meck JV. Source: Journal of Cardiovascular Pharmacology. 2003 January; 41(1): 31-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12500019
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Temporary hypotension following endarterectomy for severe carotid stenosis: should we treat it? Author(s): Gibbs BF. Source: Vascular and Endovascular Surgery. 2003 January-February; 37(1): 33-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12577137
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Terlipressin versus norepinephrine to correct refractory arterial hypotension after general anesthesia in patients chronically treated with renin-angiotensin system inhibitors. Author(s): Boccara G, Ouattara A, Godet G, Dufresne E, Bertrand M, Riou B, Coriat P. Source: Anesthesiology. 2003 June; 98(6): 1338-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12766641
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The effect of meals at different mealtimes on blood pressure and symptoms in geriatric patients with postprandial hypotension. Author(s): Vloet LC, Smits R, Jansen RW. Source: The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences. 2003 November; 58(11): 1031-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14630885
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The incidence and risk factors for hypotension after spinal anesthesia induction: an analysis with automated data collection. Author(s): Hartmann B, Junger A, Klasen J, Benson M, Jost A, Banzhaf A, Hempelmann G. Source: Anesthesia and Analgesia. 2002 June; 94(6): 1521-9, Table of Contents. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12032019
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The influence of autonomic neuropathy on hypotension during hemodialysis. Author(s): Calvo C, Maule S, Mecca F, Quadri R, Martina G, Cavallo Perin P. Source: Clinical Autonomic Research : Official Journal of the Clinical Autonomic Research Society. 2002 April; 12(2): 84-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12102455
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The role of blood volume reduction in the genesis of intradialytic hypotension. Author(s): Andrulli S, Colzani S, Mascia F, Lucchi L, Stipo L, Bigi MC, Crepaldi M, Redaelli B, Albertazzi A, Locatelli F. Source: American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation. 2002 December; 40(6): 1244-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12460044
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The use of vasopressin to treat catecholamine-resistant hypotension after phaeochromocytoma removal. Author(s): Tan SG, Koay CK, Chan ST. Source: Anaesthesia and Intensive Care. 2002 August; 30(4): 477-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12180588
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Tolerance to tacrine, arterial hypotension and leuko-araiosis in Alzheimer's disease. Author(s): Lebert F, Mouly C, Pasquier F. Source: Age and Ageing. 1998 September; 27(5): 654. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12675108
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Transient orthostatic hypotension is common in adolescents. Author(s): Stewart JM. Source: The Journal of Pediatrics. 2002 April; 140(4): 418-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12006955
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Treatment of orthostatic hypotension. Author(s): Oldenburg O, Kribben A, Baumgart D, Philipp T, Erbel R, Cohen MV. Source: Current Opinion in Pharmacology. 2002 December; 2(6): 740-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12482740
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Treatment of patients with orthostatic hypotension and syncope. Author(s): Kaufmann H. Source: Clinical Neuropharmacology. 2002 May-June; 25(3): 133-41. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12023567
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Unusual causes of severe orthostatic hypotension. Author(s): Nasar MA, Murty S. Source: Hosp Med. 2002 April; 63(4): 240-1. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11995278
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Useful interventions for intradialytic hypotension. Author(s): Sherman RA. Source: Int J Artif Organs. 2003 October; 26(10): 889-91. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14636003
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Vasopressin reversal of phenoxybenzamine-induced hypotension after the Norwood procedure. Author(s): O'Blenes SB, Roy N, Konstantinov I, Bohn D, Van Arsdell GS. Source: The Journal of Thoracic and Cardiovascular Surgery. 2002 May; 123(5): 1012-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12019395
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Widespread cardiovascular autonomic dysfunction in primary amyloidosis: does spontaneous hyperventilation have a compensatory role against postural hypotension? Author(s): Bernardi L, Passino C, Porta C, Anesi E, Palladini G, Merlini G. Source: Heart (British Cardiac Society). 2002 December; 88(6): 615-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12433892
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CHAPTER 2. NUTRITION AND HYPOTENSION Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and hypotension.
Finding Nutrition Studies on Hypotension 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 “hypotension” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.
7 Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.
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The following is a typical result when searching for recently indexed consumer information on hypotension: •
The topsy-turvy world of postural hypotension. Source: D'Arrigo, T. Diabetes-forecast. (1999). March 1999. volume 52 (3) page 76-79.
The following information is typical of that found when using the “Full IBIDS Database” to search for “hypotension” (or a synonym): •
Bisxanthones from Hypericum japonicum: inhibitors of PAF-induced hypotension. Author(s): School of Pharmaceutical Sciences, Mukogawa Women's University, Koshien Kyuban-cho, Hyogo, Japan.
[email protected] Source: Ishiguro, Kyoko Nagata, Satoko Oku, Hisae Yamaki, Masae Planta-Med. 2002 March; 68(3): 258-61 0032-0943
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Cerebral oxygenation during prostaglandin E1 induced hypotension. Author(s): Department of Anaesthesiology and Reanimatology, Gunma University, School of Medicine, Japan. Source: Kadoi, Y Saito, S Kunimoto, F Morita, T Goto, F Kawahara, F Fujita, N Can-JAnaesth. 1998 September; 45(9): 860-4 0832-610X
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Effect of levodopa on orthostatic and postprandial hypotension in elderly Parkinsonian patients. Author(s): Department of Geriatric Medicine, University Medical Center, Nijmegen, The Netherlands. Source: Mehagnoul Schipper, D J Boerman, R H Hoefnagels, W H Jansen, R W JGerontol-A-Biol-Sci-Med-Sci. 2001 December; 56(12): M749-55 1079-5006
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Failure of L-arginine to induce hypotension in patients with a history of acceleratedmalignant hypertension. Author(s): Department of Internal Medicine, Nagoya City Johoku Hospital, Japan. Source: Sato, K Kinoshita, M Kojima, M Miyagawa, K Takase, H Suzuki, S Dohi, Y JHum-Hypertens. 2000 August; 14(8): 485-8 0950-9240
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Hypotension following acute hypovolaemia depends on the caudal midline medulla. Author(s): Department of Anatomy and Histology, The University of Sydney, NSW, Australia. Source: Henderson, L A Keay, K A Bandler, R Neuroreport. 1998 June 1; 9(8): 1839-44 0959-4965
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Indomethacin attenuates post-suspension hypotension in Sprague-Dawley rats. Author(s): Depts. of Pharmacology/Toxicology, Morehouse School of Medicine, Atlanta, Georgia, USA.
[email protected] Source: Bayorh, M A Eatman, D Wang, M Socci, R R Emmett, N Thierry Palmer, M JGravit-Physiol. 2001 December; 8(2): 77-83 1077-9248
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Is vasopressin an ideal vasopressor to treat hypotension in septic shock? Source: Romand, J A Treggiari Venzi, M Intensive-Care-Med. 1999 July; 25(7): 763-4 0342-4642
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L-threo-dihydroxyphenylserine (L-threo-DOPS; droxidopa) in the management of neurogenic orthostatic hypotension: a multi-national, multi-center, dose-ranging study in multiple system atrophy and pure autonomic failure. Author(s): Neurovascular Medicine Unit, Division of NeuroScience and Psychological Medicine, Imperial College of Science, Technology, and Medicine at St Mary's, London, UK.
[email protected]
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Source: Mathias, C J Senard, J M Braune, S Watson, L Aragishi, A Keeling, J E Taylor, M D Clin-Auton-Res. 2001 August; 11(4): 235-42 0959-9851 •
Oral clonidine reduces the requirement of prostaglandin E1 for induced hypotension. Author(s): Department of Anesthesiology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Japan. Source: Murakami, K Mammoto, T Kita, T Imai, Y Mashimo, T Kirita, T Sugimura, M Kishi, Y Can-J-Anaesth. 1999 November; 46(11): 1043-7 0832-610X
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Paeoniflorin reverses guanethidine-induced hypotension via activation of central adenosine A1 receptors in Wistar rats. Author(s): Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan City, Taiwan, ROC.
[email protected] Source: Cheng, J T Wang, C J Hsu, F L Clin-Exp-Pharmacol-Physiol. 1999 October; 26(10): 815-6 0305-1870
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Preoperative dextrose does not affect spinal-induced hypotension in elective Cesarean section. Author(s): Department of Anaesthesia, BC Women's Hospital and Health Centre, Vancouver, Canada. Source: Wilson, D Douglas, J Heid, R Rurak, D Can-J-Anaesth. 1999 November; 46(11): 1024-9 0832-610X
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Recombinant tissue factor pathway inhibitor prevents lipopolysaccharide-induced systemic hypotension in rats by inhibiting excessive production of nitric oxide. Author(s): Department of Laboratory Medicine, Kumamoto University School of Medicine, Japan. Source: Enkhbaatar, P Okajima, K Uchiba, M Isobe, H Okabe, H Thromb-Haemost. 2001 December; 86(6): 1573-7 0340-6245
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Superior mesenteric artery dilatation alone does not account for glucose-induced hypotension in human sympathetic denervation. Author(s): Division of Neuroscience and Psychological Medicine, Imperial College School of Medicine at St. Mary's, London, UK. Source: Puvi Rajasingham, S Kimber, J Watson, L P Mathias, C J J-Auton-Nerv-Syst. 1999 February 15; 75(2-3): 184-91 0165-1838
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The influence of low-, normal-, and high-carbohydrate meals on blood pressure in elderly patients with postprandial hypotension. Author(s): Department of Geriatric Medicine, University Medical Center Nijmegen, The Netherlands. Source: Vloet, L C Mehagnoul Schipper, D J Hoefnagels, W H Jansen, R W J-Gerontol-ABiol-Sci-Med-Sci. 2001 December; 56(12): M744-8 1079-5006
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Urocortin and inflammation: confounding effects of hypotension on measures of inflammation. Author(s): Developmental Endocrinology Branch, National Institute of Child Health and Human Development, Bethesda, MD 20892-1862, USA.
[email protected] Source: Torpy, D J Webster, E L Zachman, E K Aguilera, G Chrousos, G P Neuroimmunomodulation. 1999 May-June; 6(3): 182-6 1021-7401
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Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: •
healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0
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The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov
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The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov
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The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/
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The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/
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Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/
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Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/
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Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/
Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: •
AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats
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Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html
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Google: http://directory.google.com/Top/Health/Nutrition/
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Healthnotes: http://www.healthnotes.com/
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Open Directory Project: http://dmoz.org/Health/Nutrition/
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Yahoo.com: http://dir.yahoo.com/Health/Nutrition/
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WebMD®Health: http://my.webmd.com/nutrition
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
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The following is a specific Web list relating to hypotension; 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 Pyridoxine Source: Integrative Medicine Communications; www.drkoop.com Vitamin B6 (Pyridoxine) Source: Integrative Medicine Communications; www.drkoop.com
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Minerals Calcium Channel–Blockers Source: Prima Communications, Inc.www.personalhealthzone.com
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Food and Diet Low-Salt Diet Source: Healthnotes, Inc.; www.healthnotes.com
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CHAPTER 3. DISSERTATIONS ON HYPOTENSION Overview In this chapter, we will give you a bibliography on recent dissertations relating to hypotension. 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 “hypotension” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on hypotension, we have not necessarily excluded nonmedical dissertations in this bibliography.
Dissertations on Hypotension 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 hypotension. 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: •
Acute Radiation Hypotension in the Rabbit a Model for the Human Radiation Shock Syndrome by Makale, Milan Theodore; PhD from University of Alberta (Canada), 1987 http://wwwlib.umi.com/dissertations/fullcit/NL41174
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Cererovascular Responses to Hypotension and Hypercapnia in the Rabbit Effect of Alpha-receptor Blockade and Carotid Artery Occlusion by Tuor, Ursula Irene; PhD from The University of Western Ontario (Canada), 1983 http://wwwlib.umi.com/dissertations/fullcit/NK56123
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Studies of the Response to Hemorrhagic Hypotension in the Domestic Fowl, Gallus Domesticus by Wyse, David George; ADVDEG from Mcgill University (Canada), 1969 http://wwwlib.umi.com/dissertations/fullcit/NK04600
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The Role of the Central Nervous System in Hemorrhagic Hypotension by Stern, Leslie; PhD from Mcgill University (Canada), 1978 http://wwwlib.umi.com/dissertations/fullcit/NK38343
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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 4. CLINICAL TRIALS AND HYPOTENSION Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning hypotension.
Recent Trials on Hypotension The following is a list of recent trials dedicated to hypotension.8 Further information on a trial is available at the Web site indicated. •
A Phase IV Study in Subjects with Neurogenic Orthostatic Hypotension Condition(s): Hypotension, Orthostatic Study Status: This study is currently recruiting patients. Sponsor(s): Shire Pharmaceutical Development Purpose - Excerpt: We are seeking male and female patients to voluntarily take part in a clinical research study. Patients must be aged 18 or older and diagnosed with symptomatic orthostatic hypotension (low blood pressure while in the upright position) due to Parkinson's disease, multiple system atrophy, pure autonomic failure or autonomic neuropathies (i.e. neurogenic orthostatic hypotension). Symptoms of low blood pressure include dizziness, lightheadedness, changes in vision and generalized weakness upon standing. The main effect of the drug being studied is to increase blood pressure in the upright position so symptoms will decrease. The purpose of this clinical study is to further assess the clinical effect of high dose midodrine hydrochloride (ProAmatine(r)), an approved treatment for orthostatic hypotension. During the course of the study, participants will receive either ProAmatine(r) or a placebo. Assessments will be made using questionnaires that measure symptom and activity levels. Blood pressure in the lying down, sitting and standing positions will be measured. Patients will also complete standing time assessments. They will be asked to remain standing without moving until they feel sufficiently lightheaded, or dizzy, or feel faint so that they would feel more comfortable sitting down. Phase(s): Phase IV
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These are listed at www.ClinicalTrials.gov.
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Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00046163 •
A Study for Patients with Neurogenic Orthostatic Hypotension Condition(s): Hypotension, Orthostatic Study Status: This study is currently recruiting patients. Sponsor(s): Shire Pharmaceutical Development Purpose - Excerpt: We are seeking male and female patients to voluntarily take part in a clinical research study. Patients must be aged 18 or older and diagnosed with symptomatic orthostatic hypotension (low blood pressure while in the upright position) due to Parkinson's disease, multiple system atrophy, pure autonomic failure or autonomic neuropathies (i.e. neurogenic orthostatic hypotension). Symptoms of low blood pressure include dizziness, lightheadedness, changes in vision and generalized weakness upon standing. The main effect of the drug being studied is to increase blood pressure in the upright position so symptoms will decrease. The purpose of this clinical study is to further assess the clinical benefit of midodrine hydrochloride (ProAmatine(r)), an approved treatment for orthostatic hypotension. During the course of the study, participants will receive either ProAmatine(r) or a placebo. Assessments will be made using questionnaires that measure symptom and activity levels. Blood pressure in the lying down and standing positions will be measured at each visit. Phase(s): Phase IV Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00046475
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Droxidopa in Treating Patients With Neurogenic Hypotension Condition(s): Shy-Drager Syndrome; Orthostatic Hypotension Study Status: This study is currently recruiting patients. Sponsor(s): Mount Sinai Medical Center Purpose - Excerpt: RATIONALE: Neurogenic hypotension is a fall in blood pressure that occurs when one moves from a lying down to a standing position or after eating a meal. It causes one to feel dizzy, light headed, and weak. Neurogenic hypotension is caused by a problem in the part of the nervous system that controls such functions as heart rate and blood pressure. Droxidopa, a drug that may increase blood pressure, may be an effective treatment for neurogenic hypotension. PURPOSE: Clinical trial to study the effectiveness of droxidopa in treating patients who have neurogenic hypotension. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004478
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Evaluation of M40403 for the Prevention of Dose Limiting Toxicities of High Dose IL2 Condition(s): IL-2 Induced Hypotension
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Study Status: This study is suspended. Sponsor(s): MetaPhore Pharmaceuticals Purpose - Excerpt: The clinical use of IL-2 is currently limited by development of dosedependent hypotension (systolic blood pressure (SBP) < 90 mm Hg). The overall outcome is constant across sites with 20-50% of the patients requiring ICU management because of unresponsive hypotension and hyporeactivity (loss of response to vasoconstrictors). Because of the dose-limiting side effects, the duration of IL-2 dosing is frequently curtailed. Thus, hemodynamic toxicities have limited the usefulness of IL-2 therapy. M40403 has prevented both the hypotension and hyporeactivity associated with IL-2 treatment in preclinical studies. This trial will study the safety and efficacy of M40403 in the prevention or reduction of hypotension in patients receiving IL-2 therapy. Phase(s): Phase I; Phase II; MedlinePlus consumer health information Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00033956 •
Phase II Study of Midodrine for Neurogenic Orthostatic Hypotension Condition(s): Orthostatic Hypotension Study Status: This study is completed. Sponsor(s): National Center for Research Resources (NCRR); Roberts Pharmaceutical Purpose - Excerpt: Objectives: I. Study further the safety and efficacy of the alphareceptor agonist midodrine in patients with neurogenic orthostatic hypotension. II. Assess the quality of life in these patients with this treatment regimen. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004268
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 “hypotension” (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:
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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 5. PATENTS ON HYPOTENSION 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 “hypotension” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on hypotension, we have not necessarily excluded nonmedical patents in this bibliography.
Patents on Hypotension By performing a patent search focusing on hypotension, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We will tell you how to obtain this information later in the chapter. The following is an 9Adapted
from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.
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example of the type of information that you can expect to obtain from a patent search on hypotension: •
11 cby genomic sequence Inventor(s): Bergsma; Derk (Berwyn, PA), Ellis; Catherine E. (Glassboro, NJ), Halsey; Wendy (Kenneth Square, PA), Sathe; Ganesh (King of Prussia, PA) Assignee(s): Smithkline Beecham Corporation (philadelphia, Pa) Patent Number: 6,362,326 Date filed: December 22, 1998 Abstract: The present invention relates to 11cby, in particular 11cby polypeptides and 11cby polynucleotides, recombinant materials and methods for their production. In another aspect, the invention relates to methods for using such polypeptides and polynucleotides, including the treatment of bacterial, fungal, protozoan and viral infections, particularly infection caused by HIV-1 or HIV-2; pain; cancers; diabetes; obesity; feeding and drinking abnormalities, such as anorexia and bulimia; asthma; Parkinson's disease; both acute and congestive heart failure; hypotension; hypertension; urinary retention; osteoporosis; angina pectoris; myocardial infarction; ulcers; allergies; benign prostatic hypertrophy and psychotic and neurological disorders, including anxiety, schizophrenia, manic depression, delirium, dementia or severe mental retardation, and dyskinesias, such as Huntington's disease or Gilles dela Tourett's syndrome, hereinafter referred to as "the Diseases", among others. In a still further aspect, the invention relates to diagnostic and prognostic assays for detecting diseases associated with inappropriate 11cby activity or levels. A method of performing genetic association studies for searching a disease susceptibility and/or drug response genes comprising using polymorphic markers in 11cby polynucleotides. Excerpt(s): This invention overall relates to the field of human genetics. More particularly, this invention relates to newly identified polypeptides and polynucleotides encoding such polypeptides, to the use of polynucleotides in gene therapy, and to production of such polypeptides and polynucleotides. In another aspect, this invention relates to prognostic and diagnostic methods for human diseases. This invention also relates to a method of performing genetic association studies for searching a disease susceptibility and/or drug response genes comprising using polymorphic markers. Yet in further aspect, the invention relates to transgenic animals, and use of transgenic animals for disease models to screening for therapeutic compounds. 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 superceding 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. Functional genomics relies heavily on the various tools of bioinformatics to identify gene sequences of potential interest from the many molecular biology databases now available. There is a continuing need to identify and characterise further genes and their related polypeptides/proteins, as targets for drug discovery. Web site: http://www.delphion.com/details?pn=US06362326__
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Administration of an.alpha.2-adrenergic receptor agonist to enhance cardiopulmonary resuscitation Inventor(s): Bisera; Jose (Camarillo, CA), Tang; Wanchun (Palm Desert, CA), Weil; Max Harry (Northbrook, IL) Assignee(s): Institute of Critical Care Medicine (palm Springs, Ca) Patent Number: 6,369,114 Date filed: November 30, 1999 Abstract: Methods, formulations and kits are described for resuscitating a patient suffering from cardiac arrest, for enhancing the efficacy of cardiopulmonary resuscitation, for treating post-resuscitation hypotension, and for reducing the incidence of ventricular arrhythmias and myocardial dysfunction in a patient following cardiopulmonary resuscitation. Prior methods and agents often cause inotropic or chronotropic effects, which can lead to undesirable post-resuscitation myocardial dysfunction. The invention comprises administering a therapeutically effective amount of an.alpha.sub.2 -receptor agonist that does not cross the blood-brain barrier, such as.alpha.-methylnorepinephrine, to enhance cardiopulmonary resuscitation. Excerpt(s): The present invention relates generally to cardiopulmonary resuscitation, i.e., restoration of a patient's respiration and blood circulation following cardiac arrest. More particularly, the invention relates to a method for enhancing cardiopulmonary resuscitation by systemic administration of an.alpha.sub.2 -adrenergic receptor agonist. The invention finds utility in the areas of pharmacology, cardiology and general medicine. In cardiac arrest, a patient's heart ceases its normal pumping action and frequently devolves into ventricular fibrillation. Without restoration of circulation, death from anoxia is rapid. Cardiac arrest is a major cause of death and can arise from a variety of circumstances, including heart disease, electric shock and other trauma, suffocation, and the like. To improve the likelihood of patient survival and reduce the likelihood of damage to the brain and heart resulting from oxygen deprivation, it is essential that a patient's respiration and blood circulation be restored as soon as possible. A number of resuscitation techniques have been developed with the aforementioned objectives in mind. Generally, cardiopulmonary resuscitation (CPR) techniques are used that rely on external chest compression. Standardized cardiopulmonary restoration (CPR) techniques are described in "Guidelines for CPR and Emergency Cardiac Care," J. Am. Med. Assoc. 268:2205-2211 (1992), which sets out in detail the recommended procedures for administration of drugs and physical intervention in CPR. Manual CPR techniques rely on the application of a downward force on the patient's chest in order to force blood from the heart and expel air from the lungs. Ventilation by either mouth-to-mouth or mechanical techniques is performed concurrently with chest compression in order to force air back into the patient's lungs. Such manual CPR techniques, however, rely in large part on the natural elasticity of the chest in order to actively draw venous blood back into the heart, which is generally inefficient. Long-term survival in cardiac arrest patients who have undergone manual CPR is usually below 10%. Web site: http://www.delphion.com/details?pn=US06369114__
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Alpha 1a adrenergic receptor antagonists Inventor(s): Bock; Mark G. (Hatfield, PA), Patane; Michael A. (Harleysville, PA), Selnick; Harold G. (Ambler, PA) Assignee(s): Merck & Co., Inc. (rahway, Nj) Patent Number: 6,255,315 Date filed: December 9, 1999 Abstract: This invention relates to certain novel compounds and derivatives thereof, their synthesis, and their use as alpha 1a adrenergic receptor antagonists. One application of these compounds is in the treatment of benign prostatic hyperplasia. These compounds are selective in their ability to relax smooth muscle tissue enriched in the alpha 1a receptor subtype without at the same time inducing hypotension. One such tissue is found surrounding the urethral lining. Therefore, one utility of the instant compounds is to provide acute relief to males suffering from benign prostatic hyperplasia, by permitting less hindered urine flow. Another utility of the instant compounds is provided by combination with a human 5-alpha relductase inhibitory compound, such that both acute and chronic relief from the effects of benign prostatic hyperplasia are achieved. Excerpt(s): This invention relates to certain novel compounds and derivatives thereof, their synthesis, and their use as alpha 1a adrenoceptor antagonists. More particularly, the compounds of the present invention are useful for treating benign prostatic hyperplasia (BPH). Human adrenergic receptors are integral membrane proteins which have been classified into two broad classes, the alpha and the beta adrenergic receptors. Both types mediate the action of the peripheral sympathetic nervous system upon binding of catecholamines, norepinephrine and epinephrine. Norepinephrine is produced by adrenergic nerve endings, while epinephrine is produced by the adrenal medulla. The binding affinity of adrenergic receptors for these compounds forms one basis of the classification: alpha receptors bind norepinephrine more strongly than epinephrine and much more strongly than the synthetic compound isoproterenol. The binding affinity of these hormones is reversed for the beta receptors. In many tissues, the functional responses, such as smooth muscle contraction, induced by alpha receptor activation are opposed to responses induced by beta receptor binding. Web site: http://www.delphion.com/details?pn=US06255315__
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Apparatus for artificial kidney, quality evaluating device for dialyzing fluid and dialyzing means using the same, and fluid circuit Inventor(s): Endo; Fumiaki (Shizuoka, JP), Kamibayashi; Masato (Kanagawa, JP), Motoyama; Shinji (Kanagawa, JP), Sawamoto; Jiro (Kanagawa, JP) Assignee(s): Asahi Medical Co., Ltd. (tokyo, Jp) Patent Number: 6,555,058 Date filed: December 22, 2000 Abstract: An apparatus which can solve the problem of participation of NO in hypotension in dialysis, hypoxia in dialysis, and the like during artificial dialysis by continuously monitoring fluctuation in a blood gas, an ionic component, or the like in body fluid such as blood and by suppressing these diseases, and quality evaluating means of an artificial dialyzer and dialyzing fluid are provided. An apparatus for an
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artificial kidney comprises a measurement monitor for continuously measuring nitric oxide as a component of body fluid or liquid for treatment. Further, an apparatus for an artificial kidney comprises a measurement monitor for measuring a component of body fluid or liquid for treatment, a display means for comparing a measurement measured by the measurement monitor with a control value, and when the measurement equals the control value, displays the equality, and oxygen supplying means. Excerpt(s): The present invention relates to an apparatus for an artificial kidney for continuously measuring a component in body fluid such as blood or plasma, or liquid for treatment such as dialyzing fluid or supplementary liquid, or for measuring it and further adjusting the partial pressure of oxygen in the body fluid or in the liquid for treatment using oxygen supplying means, to a fluid circuit used in such an apparatus, and a quality evaluating device using such an apparatus for artificial kidney and its fluid circuit. The present invention also relates to a method of preventing or treating hypotension and hypoxia associating with artificial dialysis in treatment using an apparatus for an artificial kidney by controlling partial pressure of oxygen in body fluid. Abnormal living body cases of an artificial dialysis patient include hypotension in dialysis (Mariko Kato, Journal of Japanese Society of Nephrology, Vol. 29, pp. 1249-1259 (1987)), hypoxia in dialysis where the partial pressure of oxygen in artery is decreased (Takumi Okamoto, Medical Journal of Hiroshima University, Vol. 35, pp. 1031-1081 (1987) and Jacob A. J. et al., Kidney International, Vol. 18, pp. 505-509 (1980)), and the like. It has been pointed out that decrease in the partial pressure of oxygen in the blood during dialysis (hereinafter referred to as P.sub.0.sub.sup.2 ) is part of the onset mechanism of the hypotension in dialysis that previously described in literatures. Recently, it has been pointed out that, during dialysis, a large amount of nitric oxide (hereinafter referred to as NO) having a strong vasodilator action is produced in the blood through the stimulus of cytokine, endotoxin, or the like, which participates in the onset mechanism of the hypotension in dialysis. Web site: http://www.delphion.com/details?pn=US06555058__ •
Arylhydantoin derivatives and uses thereof Inventor(s): Bock; Mark G. (Hatfield, PA), DiPardo; Robert M. (Lansdale, PA), Hoffman; Jacob M. (Lansdale, PA), Patane; Michael A. (Harleysville, PA), Payne; Linda S. (Lansdale, PA) Assignee(s): Merck & Co., Inc. (rahway, Nj) Patent Number: 6,436,962 Date filed: September 27, 2000 Abstract: Arylhydantoin derivatives and their pharmaceutically acceptable salts are disclosed. The synthesis of these compounds and their use as alpha 1a adrenergic receptor antagonists is also described. One application of these compounds is in the treatment of benign prostatic hyperplasia. These compounds are typically selective in their ability to relax smooth muscle tissue enriched in the alpha 1a receptor subtype without at the same time inducing hypotension. One such tissue is found surrounding the urethral lining. Therefore, one utility of the instant compounds is to provide acute relief to males suffering from benign prostatic hyperplasia, by permitting less hindered urine flow. Another utility of the instant compounds is provided by combination with a human 5-alpha reductase inhibitory compound, such that both acute and chronic relief from the effects of benign prostatic hyperplasia can be achieved.
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Excerpt(s): The present invention relates to arylhydantoin derivatives and pharmaceutically acceptable salts thereof, their synthesis, and their use as alpha 1a adrenoceptor antagonists. The arylhydantoin derivatives of the present invention include, but are not limited to, compounds having (1-azacycloalkyl)alkyl, ((4-amino)-1azacycloalkyl)alkyl, or (spiroazacycloalkyl)alkyl groups as side chains on a hydantoin ring nitrogen. The compounds of the present invention are useful for treating benign prostatic hyperplasia (BPH). References are made throughout this application to various publications, the disclosures of which are hereby incorporated by reference in their entireties, in order to more fully describe the state of the art to which this invention pertains. Human adrenergic receptors are integral membrane proteins which have been classified into two broad classes, the alpha and the beta adrenergic receptors. Both types mediate the action of the peripheral sympathetic nervous system upon binding of catecholamines, norepinephrine and epinephrine. Web site: http://www.delphion.com/details?pn=US06436962__ •
Blocking induction of tetrahydrobiopterin to block induction of nitric oxide synthesis Inventor(s): Gross; Steven S. (New York, NY) Assignee(s): Cornell Research Foundation, Inc. (ithaca, Ny) Patent Number: 6,274,581 Date filed: May 20, 1993 Abstract: Guanosine triphosphate pathway tetrahydrobiopterin synthesis antagonist and/or pterin salvage pathway tetrahydrobiopterin synthesis antagonist are administered to inhibit nitric oxide synthesis from arginine in vascular smooth muscle cells in a subject in need of such inhibition (e.g. for prophylactic or curative effect for cytokine-induced hypotension or for restoration of vascular contractile sensitivity to pressor agents in the treatment of such hypotension). Excerpt(s): This invention is directed to a novel method of inhibiting the induction of nitric oxide formation in biological systems by bacterial endotoxins and cytokines. For several decades nitroglycerin has been administered to humans as a vasodilating agent in the treatment of cardiovascular disease. Recently, it has been shown that nitroglycerin so administered is converted in the body to nitric oxide which is the pharmacologically active metabolite. Still more recently, nitric oxide has been shown to be formed enzymatically from arginine as a normal metabolite which is an important component of endothelium-derived relaxing factors (EDRFs). EDRFs are currently being intensively studied as participating in regulation of blood flow and vascular resistance. In addition to vascular endothelium, macrophages have also been shown to produce nitric oxide in the body which is a component of their cell killing and/or cytostatic function. More recently it has been established that the enzyme forming nitric oxide from arginine, i.e., nitric oxide synthase, occurs in two distinct forms, namely a constitutive form and an inducible form. The constitutive form is present in normal endothelial cells, neurons and some other tissues. Formation of nitric oxide by the constitutive form in endothelial cells is thought to play a role in normal blood pressure regulation. The inducible form of nitric oxide synthase has been found to be present in activated macrophages and is induced in endothelial cells and vascular smooth muscle cells, for example, by various cytokines and/or microbial products. It is thought that in sepsis or cytokine-induced shock, overproduction of nitric oxide by the inducible form of nitric oxide synthase plays an important role in the observed life-threatening hypotension. Furthermore, it is thought that overproduction of nitric oxide by the inducible form of nitric oxide
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synthase is a basis for insensitivity to clinically used pressor agents such as.alpha.sub.1. adrenergic agonists in the treatment of septic or cytokine-induced shock patients. Web site: http://www.delphion.com/details?pn=US06274581__ •
Controller for ultrafiltration blood circuit which prevents hypotension by monitoring osmotic pressure in blood Inventor(s): Gelfand; Mark (New York, NY), Levin; Howard R. (Teaneck, NJ), O'Mahony; John J. (Hackensack, NJ) Assignee(s): Chf Solutions, Inc. (new York, Ny) Patent Number: 6,689,083 Date filed: November 27, 2000 Abstract: A method and system for the extracorporeal treatment of blood to remove fluid from the fluid overloaded patient is disclosed that non-invasively measures osmotic pressure across a filter membrane of a blood filter. The filter is permeable to water and electrolytes, but not to blood protein. The osmotic pressure indicates the protein concentration in the blood. Osmotic pressure is used to detect when hypotension is about to occur in a patient, as a result of excessive blood volume reduction during treatment of the blood. Using the osmotic pressure measurement as a feedback signal, the rate of fluid extraction is automatically controlled to achieve the desired clinical outcome and avoid precipitating a hypotensive crisis in the patient. Excerpt(s): The present invention relates to an apparatus for the extracorporal treatment of blood and more specifically to the automatic control fluid removal from the blood of patients suffering from fluid overload and averting therapy induced hypotension. Renal replacement therapy (RRT) has evolved from the long, slow hemodialysis treatment regime of the 1960's to a diverse set of therapy options, the vast majority of which employ high permeability membrane devices and ultrafiltration control systems. Biologic kidneys remove metabolic waste products, other toxins, and excess water. They also maintain electrolyte balance and produce several hormones for a human or other mammalian body. An artificial kidney, also called a hemodialyzer or dialyzer, and attendant equipment and supplies are designed to replace the blood-cleansing functions of the biologic kidney. At the center of artificial kidney design is a semipermeable filter membrane that allows passage of water, electrolytes, and solute toxins to be removed from the blood. The membrane retains in the blood, the plasma proteins and other formed elements of the blood. Web site: http://www.delphion.com/details?pn=US06689083__
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Human endothelin-bombesin receptor antibodies Inventor(s): Kumar; Chandrika (West Windsor, NJ), Li; Yi (Sunnyvale, CA), Rosen; Craig A. (Laytonsville, MD) Assignee(s): Human Genome Sciences, Inc. (rockville, Md), Smithkline Beecham Corp. (philadelphia, Pa) Patent Number: 6,518,404 Date filed: March 7, 2000
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Abstract: A human endothelin-bombesin receptor polypeptide and DNA (RNA) encoding such polypeptide and a procedure for disclosed. Also disclosed are methods for utilizing such polypeptide for identifying agonists and antagonists to such polypeptide. Agonists to the endothelin-bombesin receptor polypeptide of the present invention may be used to treat asthma, Parkinson's Disease, acute heart failure, hypotension and osteoporosis. Antagonists against such polypeptides may be used therapeutically to treat hypertension, ulcerigenesis, subarachnoid hemorrhage, asthma, tumors, ciclosporin toxicity, cancer and septic shock. Also disclosed are diagnostic methods for detecting mutations in the polynucleotides of the present invention and for detecting levels of the soluble polypeptides in samples derived from a host. Excerpt(s): It is well established that many medically significant biological processes are mediated by proteins participating in signal transduction pathways that involve Gproteins and/or second messengers, e.g., cAMP (Lefkowitz, Nature, 351:353-354 (1991)). Herein these proteins are referred to as proteins participating in pathways with Gproteins or PPG proteins. Some examples of these proteins include the GPC receptors, such as those for adrenergic agents and dopamine (Kobilka, B. K., et al., PNAS, 84:46-50 (1987); Kobilka, B. K., et al., Science, 238:650-656 (1987); Bunzow, J. R., et al., Nature, 336: 783-787 (1988)), G-proteins themselves, effector proteins, e.g., phospholipase C, adenyl cyclase, and phosphodiesterase, and actuator proteins, e.g., protein kinase A and protein kinase C (Simon, M. I., et al., Science, 252:802-8 (1991)). For example, in one form of signal transduction, the effect of hormone binding is activation of an enzyme, adenylate cyclase, inside the cell. Enzyme activation by hormones is dependent on the presence of the nucleotide GTP, and GTP also influences hormone binding. A G-protein connects the hormone receptors to adenylate cyclase. G-protein was shown to exchange GTP for bound GDP when activated by hormone receptors. The GTP-carrying form then binds to an activated adenylate cyclase. Hydrolysis of GTP to GDP, catalyzed by the G-protein itself, returns the G-protein to its basal, inactive form. Thus, the G-protein serves a dual role, as an intermediate that relays the signal from receptor to effector, and as a clock that controls the duration of the signal. The peptide endothelin is a peptide of 21 amino acid residues and performs in vivo effects via endothelin receptors. Endothelin (ET) is a peptide present in various tissues in animals and is known as a strong vasoconstrictor. ET is one peptide of a family of at least 4 mammalian peptides characterized by 2 disulphide bridges and 6 conserved amino acid residues at the C-terminus. Web site: http://www.delphion.com/details?pn=US06518404__ •
Human protein kinases hYAK3-2 Inventor(s): Creasy; Caretha (Erdenheim, PA), Dillon; Susan B. (Chester Springs, PA), Lord; Kenneth A. (Collegeville, PA) Assignee(s): Smithkline Beecham Corporation (philadelphia, Pa) Patent Number: 6,323,318 Date filed: August 10, 1999 Abstract: hYAK3-2 polypeptides and polynucleotides and methods for producing such polypeptides by recombinant techniques are disclosed. Also disclosed are methods for utilizing hYAK3-2 polypeptides and polynucleotides in the design of protocols for the treatment of bone loss including osteoporosis; inflammatory diseases such as Adult Respiratory Disease Syndrome (ARDS), Rheumatoid arthritis, Osteoarthritis, Inflammatory Bowel Disease (IBD), psoriasis, dermatitis, asthma, allergies; infections such as bacterial, fungal, protozoan and viral infections, particularly infections caused
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by HIV-1 or HIV-2; HIV-associated cachexia and other immunodeficiency disorders; septic shock; pain; injury; cancers including testicular cancer; anorexia; bulimia; neutropenia; cytopenia; anemias, including anemias due to renal insufficiency or to chronic disease, such as autoimmunity or cancer, and drug-induced anemias; polycythemia; myelosuppression; Parkinson's disease; cardiovascular disease including restenosis, atherosclerosis, acute heart failure, myocardial infarction; hypotension; hypertension; urinary retention; angina pectoris; ulcers; benign prostatic hypertrophy; and psychotic and neurological disorders, including anxiety, schizophrenia, manic depression, delirium, dementia, severe mental retardation and dyskinesias, such as Huntington's disease or Gilles dela Tourett's syndrome, among others, and diagnostic assays for such conditions. Excerpt(s): This invention relates to newly identified polynucleotides, polypeptides encoded by them and to the use of such polynucleotides and polypeptides, and to their production. More particularly, the polynucleotides and polypeptides of the present invention relate to a serine/threonine protein kinase, hereinafter referred to as hYAK3-2. The invention also relates to inhibiting or activating the action of such polynucleotides and polypeptides. A number of polypeptide growth factors and hormones mediate their cellular effects through a signal transduction pathway. Transduction of signals from the cell surface receptors for these ligands to intracellular effectors frequently involves phosphorylation or dephosphorylation of specific protein substrates by regulatory protein serine/threonine kinases (PSTK) and phosphatases. Serine/threonine phosphorylation is a major mediator of signal transduction in multicellular organisms. Receptor-bound, membrane-bound and intracellular PSTKs regulate cell proliferation, cell differentiation and signalling processes in many cell types. Aberrant protein serine/threonine kinase activity has been implicated or is suspected in a number of pathologies such as rheumatoid arthritis, psoriasis, septic shock, bone loss, many cancers and other proliferative diseases. Accordingly, serine/threonine kinases and the signal transduction pathways which they are part of are potential targets for drug design. Web site: http://www.delphion.com/details?pn=US06323318__ •
Inhibition of nitric oxide-mediated hypotension and septic shock with ironcontaining hemoprotein Inventor(s): Bonaventura; Joseph (Beaufort, NC), De Angelo; Joseph (Hamtramck, MI), Kilbourn; Robert G. (Houston, TX) Assignee(s): Apex Bioscience, Inc. (research Triangle Park, Nc), Board of Regents, the University of Texas System (austin, Tx), Duke University (durham, Nc) Patent Number: 6,350,729 Date filed: July 13, 2000 Abstract: The invention is directed to a method for the prophylaxis or treatment of an animal for deleterious physiological effects such as systemic hypotension caused by nitric oxide production induced by a biological response modifier. Examples of such biological response modifiers include but are not limited to a cytokine and an endotoxin. The invention is also directed to a method for the treatment of septic shock. Excerpt(s): The invention is directed to a method for the prophylaxis or treatment of an animal for systemic hypotension induced by a biological response modifier. Examples of such biological response modifiers include but are not limited to a cytokine and an
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endotoxin. The invention is also directed to a method for the treatment of septic shock. Endothelial cells have been shown to produce a potent vasodilator known as Endothelium-Derived Relaxing Factor (EDRF). Many naturally occurring substances which act as physiological vasodilators mediate all or part of their action by stimulating the release of EDRF. Examples of such substances include acetylcholine, histamine, bradykinin, leukotrienes, ADP, and ATP. Recent studies have identified EDRF as nitric oxide, a short lived, unstable compound (Ignarro et al., 1987, Proc. Natl. Acad. Sci. U.S.A. 84:9265-9269 and Palmer et al., 1987, Nature 327:524-526). L-Arginine is the metabolic precursor of EDRF (Schmidt et al., 1988, Eur. J. Pharmacol. 154:213-216). N.sup.G -methyl-L-arginine is a competitive inhibitor of the biosynthetic pathway of EDRF (Palmer et al., 1988, Nature 333:664-666). Administration of N.sup.G -methyl-Larginine to guinea pigs and rabbits has been shown to increase blood pressure (Aisaka et al., 1989, Biochem. Biophys. Res. Commun. 160:881-886). Nitric oxide (NO) appears to be synthesized from L-arginine by the enzyme, NO synthase; the coproduct is Lcitrulline (Moncada et al., 1991, J. Cardiovascular Pharmacol. 17 (Suppl. 3):S1-S9). NO is an endogenous stimulator for soluble guanylate cyclase. Web site: http://www.delphion.com/details?pn=US06350729__ •
Methods of identifying modulators of perivascular sensory nerve Ca2+ receptors Inventor(s): Bian; Ka (League City, TX), Bukoski; Richard D. (Galveston, TX) Assignee(s): Board of Regents, the University of Texas System (austin, Tx) Patent Number: 6,184,254 Date filed: November 13, 1998 Abstract: Methods of identifying compounds that relax or stimulate arterial tension through their action on perivascular sensory nerve calcium receptors are described. Compounds identified through such methods are useful for the treatment of hypertension, hypotension and other diseases and conditions that alter normal physiological blood pressure. Excerpt(s): The present invention relates generally to the fields of endocrinology and neurobiology. More particularly it concerns the mechanisms by which extracellular Ca.sup.2+ and the steroid hormone 1,25 (OH).sub.2 vitamin D.sub.3 modulate vascular smooth muscle force generation. Essential hypertension is a major health problem in the U.S. with an estimated 50 million adults being affected (Gifford, 1993) and is characterized by an increase in peripheral resistance in the face of normal cardiac output (Folkow, 1982). There is a clear pattern of inheritance and influence of the environment (Lifton, 1996) and untreated hypertension is a significant risk factor for stroke, myocardial infarction, coronary artery disease, renal failure, and premature death (Gordon et al., 1977). Standard therapy is directed toward lowering blood volume (diuretics and salt restriction), or reduction of vascular tone (vasodilators, pressor antagonists, and sympatholytics) (The Fifth Report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure, 1993). Although medical management of hypertension has contributed to a large reduction in stroke incidence over the past two decades, reduction in risk of myocardial infarction has not shown a parallel improvement (Anderson et al., 1991). Thus, cardiovascular disease remains the number one cause of death in the U.S. Available antihypertensive compounds have unwanted side effects or clear contraindications. Diuretics and beta adrenoreceptor antagonists are indicated as first line therapy (The Fifth Report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure, 1993) but
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are associated with significant untoward effects including erectile dysfunction and fatigue (.beta.-blockers), and are contraindicated in renal failure (diuretics). These observations underscore the need for novel therapeutic approaches to hypertensive disease. One area of blood pressure research which has potential for the development of novel pharmacological strategies, but has remained untapped, is the study of the relationship between Ca.sup.2+ homeostasis and blood pressure regulation. Web site: http://www.delphion.com/details?pn=US06184254__ •
Pharmaceutical compositions comprising S-alkylisothiouronium derivatives Inventor(s): Arzamastsev; Evgeni (Moscow, RU), Bondareva; Galina (Moscow, RU), Darchuk; Victor (Kishinev, MD), Gikavy; Victor (Kishinev, MD), Jashounsky; Vladimir (Moscow, RU), Kochetkova; Marina (Moscow, RU), Kovtun; Valeri (Moscow, RU), Mizrakh; Lev (Rehovot, IL), Shagalov; Lev (Moscow, RU), Terekhova; Olga (Moscow, RU), Znamensky; Valentin (Moscow, RU) Assignee(s): Meditor Pharmaceuticals Ltd. (rehovot, Il) Patent Number: 6,160,008 Date filed: June 9, 1999 Abstract: S-Alkylisothiouronium salts with phosphorus-containing acids are described. The compounds are used in processes of treating acute hypotension, which may result, for example, from shock or hemorrhage, and in processes for treating hyperoxic conditions, for example, oxygen poisoning. Excerpt(s): The present invention relates to S-alkylisothiouronium salts with phosphorus-containing acids which affect arterial blood pressure and possess oxygen protective activity, and to the use of such compounds in cases of acute and chronic hypotension (hemorrhage, trauma, shock, poisoning), especially for first aid, as well as in cases of oxygen poisoning. Most medicaments affecting arterial blood pressure act either via the stimulation of alpha-adrenergic receptors or directly on the visceral muscles of the vascular wall. Adrenomimetics, e.g. adrenaline, noradrenaline, adrianol, phenylephrine (mezaton) ephedrine, ethylephrine, etc., and polypeptides, e.g. glucogon, angiotensin, octapressin, etc. are most often used. Mezaton is a well known adrenomimetic drug (M. D. Mashkovsky, Medicines, 12-th edd., Moscow., Medicine, 1993, Part I, p. 303), having a pharmaceutical activity related to that of the compounds of the present invention. Mezaton (1-(m-hydroxyphenyl)-2-methylaminoethanol hydrochloride) selectively stimulates.alpha.1-adrenoreceptors, causes arterial constriction and increase in systolic and diastolic pressure (with possible reflectoral bradycardia). Mezaton practically does not have cardiostimulating effect. Unlike adrenaline and noradrenoline, mezaton is not a catecholamine (it contains only one hydroxyl group in aromatic nucleus) and is not influenced by the enzyme--catechole-Omethyltransferase, therefore it is more stable and has a prolonged effect. Mezaton's antihypotensive effect usually lasts for approximately 20 minutes after a single intravascular injection. Web site: http://www.delphion.com/details?pn=US06160008__
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Self applied and self adjusting device and method for prevention of deep vein thrombosis with movement detection Inventor(s): Katz; Amiram (15 Beaver Brook Rd., Weston, CT 06883), Katz; Orly (15 Beaver Brook Rd., Weston, CT 06883) Assignee(s): None Reported Patent Number: 6,282,448 Date filed: May 18, 1999 Abstract: An elongated rectangular cuff having electrodes combined with a motion detector for detecting muscle contraction with an attached control unit for providing a predetermined electrical signal to the electrodes. The predetermined electrical signal is substantially a square wave with a duration of between 0.1 and 0.3 milliseconds, a frequency of between 0.1 and 0.5 Hertz, with 5 to 15 repetitions delivered every 5 to 15 minute intervals. The control unit provides a controllable intensity of between 0.20 to 4 milliamperes, and a voltage between 1 and 200 volts at an output resistance of substantially 50 kilo Ohms. The cuff or sleeve, when wrapped around a user's leg and positioned below the knee such that the electrodes contact the calf muscles, causes a muscle and nerve stimulation resulting in contraction of the calf muscle. A motion detector monitors the contraction and provides feedback to the control unit to adjust the signal. Blood flow is therefore increased regardless of body position or movement greatly decreasing the possibility of developing deep vein thrombosis or pulmonary embolism, which may be fatal. In addition it reduces ankle edema and leg discomfort associated with prolonged sitting. In addition it prevents orthostatic hypotension. An applied signal is continuously adjusted resulting in little risk of harm to the user. Excerpt(s): This invention relates to an electronic stimulator, and more specifically to an electronic nerve and muscle stimulator and method useful for preventing venous thrombo embolism, venostasis, varicose veins, orthostatic hypotension, ankle edema, and leg discomfort resulting from prolonged sitting that can be self administered by a patient. There are a large number of diagnosed cases of deep vein thrombosis, DVT, in the United States annually. There are also a large number of fatal cases of pulmonary embolism, PE, many of which can be prevented with appropriate measures, such as pharmacological or mechanical. Prolonged sitting, such as when traveling or working long hours, can aggravate or promote DVT or PE. It can also cause ankle edema and leg discomfort. Studies have indicated that about one-fifth of the sudden natural deaths associated with commercial air travel that were brought to the London Coroner from Heathrow Airport were due to pulmonary embolism. There is a need for a device that helps to stimulate blood flow so as to prevent DVT and PE during the above mentioned circumstances. One such device is disclosed in U.S. Pat. No. 5,643,331 entitled "Method and Device For Prevention of Deep Vein Thrombosis" issuing to Katz on Jul. 1, 1997, which is herein incorporated by reference. Therein disclosed is an electrical stimulator generating a square wave pattern having a controllable duration ranging from 0.1 to 0.3 milliseconds, a controllable frequency ranging between 0.001 to 0.5 cycles per second, and a controllable intensity ranging from 1 to 20 milliamperes. An electrode is positioned externally at or near the tibial nerve at the popliteal fossa to deliver the electrical signal. This signal stimulates the nerve, causing a muscle contraction which helping to stimulate blood flow. The increased blood flow helps in preventing deep vein thrombosis, ankle edema, and venostasis. Additionally, there are numerous transcutaneous electric nerve stimulating devices, TENS units, used to control pain. There are also similar muscle and neurological stimulating devices, MANS units, also used to control or manage pain. All of these devices deliver relatively high frequency
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stimuli, for example 25 to 50 Hertz. They are generally not tolerated well by patients, especially when used for relatively long periods of time. Additionally, these devices are not completely suitable for the prevention of DVT or PE. Accordingly, while these units used for pain management or control are similar, they are not suited to relatively long term use and self-application by a patient for the prevention of DVT, orthostatic hypotension, PE ankle edema and leg discomfort. Therefore, there is a need for a device and method of application that can easily be self-administered by a patient during extended periods of sitting or inactivity, for example during traveling in a car or a plane, or sitting for many hours while working to help prevent DVT, PE ankle edema and leg discomfort. Additionally, there is a need for a device that is self adjusting preventing the need for a patient to determine appropriate settings. Additionally, there is a need for a device that will sense the muscle contraction and will not operate during on going muscle activity. The present invention comprises a self-contained electrical device having pre-positioned electrodes making it easy to be self-applied by a patient and worn for extended periods of time during periods of inactivity or immobility, such as when paralyzed, hospitalized or sitting during traveling or working that is self adjusting. An elongated rectangular cuff or sleeve has straps and strips of hook and loop fastener material. Two electrodes having a predetermined position are connected to a control unit. Indicia or marking on the sleeve is placed between the two electrodes to aid in the proper positioning of the electrodes onto the leg of a patient or user. The indicia helps the user to position the electrodes without any specific knowledge of anatomy. The cuff or sleeve is sized to wrap around the calf of a user and to be securely held thereto in a proper predetermined position. The control unit attached to the cuff is preset to provide a substantially square wave signal to the electrodes having a duration of 0.3 milliseconds, a frequency of 0.1 to 0.5 Hertz with 5 to 15 repetitions delivered every 5 to 15 minutes. In one embodiment, the control unit has a structure permitting a user to control intensity only, and only within a range of 1 to 200 volts and 0.02 to 4 milliamperes at a 50 kilo Ohm output resistanc. In this embodiment, the intensity control is the only user controlled adjustment, which may also be the on/off control. In another embodiment the control is automatically adjusted. A motion detector or its equivalent, such as a stain gage or accelerometer is used to detect movement or contraction of the patients calf in response to a signal provided by the electrodes. The signal is adjusted according to the detected movement or contraction. In this embodiment, the activity sufficient to provide adequate blood flow can be detected and the signal or current output stopped during the activity. Web site: http://www.delphion.com/details?pn=US06282448__ •
Triple drug therapy for the treatment of narcotic and alcohol withdrawal symptoms Inventor(s): Ockert; David M. (145 E. 32nd St., Sixth Floor, New York, NY 10016) Assignee(s): None Reported Patent Number: 6,503,950 Date filed: August 8, 2000 Abstract: A triple drug, pharmaceutical kit, composition, and method of treatment containing a combination of effective amounts of at least one anxiolytic agent, at least one centrally acting alpha antiadrenergic agent, and at least one central nervous system stimulant for the reduction or prevention of alcohol and narcotic withdrawal side effects of dizziness, drowsiness, depression, lethargy, orthostatic hypotension, weakness in the extremities, and difficulty in being mobile, caused by therapeutic agents utilized for the
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treatment of alcohol or narcotic withdrawal symptoms in patients overcoming alcohol or narcotic addiction. Excerpt(s): The present invention relates to the treatment of alcohol and narcotic withdrawal symptoms associated with alcohol and narcotic addiction. Alcohol and narcotic withdrawal symptoms associated with patient populations undergoing drug abuse treatment has become an important concern to those patients and their families as well as treating health care personnel. Due to alcohol and narcotic abuse, use, and the high rate of relapse to regular use, the management of withdrawal side effects is becoming increasingly important for the long-term rehabilitation of patients overcoming drug abuse addiction. Current treatment modalities for drug abuse can create or potentiate side effects from those medications used to treat alcohol or narcotic withdrawal. Frequently encountered side effects include depression, dizziness, orthostatic hypotension, drowsiness, lethargy, difficulty in being mobile, and weakness in the extremities. Such negative side effects prolong patient therapy or interfere with detoxification procedures, which leads to further use, abuse, and relapses to regular use, requiring subsequent detoxification. treatment episodes. The prior art teaches the use of benzodiazepines separately for the treatment of anxiety caused by a variety of conditions, including withdrawal. For example, the drug monograph for benzodiazepines listed within the Drug Facts and Comparisons, 1999 ed., Wolters Kulwar Co. 1998, p. 1600-03, indicates that such agents, through interaction with gamma-aminobutyrate (GABA) and BZ.sub.1 and BZ.sub.2 receptors in the human body, create a calming effect and subsequent reduction or prevention of anxiety. The prior art also teaches the use of azaspirodecanediones, such as buspirone, as an anxiolytic agent, because of their calming effect caused by interaction with 5-HT.sub.1 A and GABA receptors in the human body. Id. Finally, the prior art also teaches the use of piperazine derivatives, such as hydroxyzine, to create a calming effect in the human body through interaction with spasmogenic receptors for serotonin, acetylcholine and histamine. Id. at 1604-07. Yet, all these anxiolytic agents, due to their drug chemistry, cause the side effects of drowsiness, depression, lethargy, and difficulty in being mobile in patients undergoing drug abuse treatment. Such negative side effects frequently increase the need to treat such patients in an in-patient only setting to prevent the risk of injury. Web site: http://www.delphion.com/details?pn=US06503950__ •
Use of selective antagonists of the.alpha.1B-adrenergic receptor for improvement of sexual dysfunction Inventor(s): Leonardi; Amedeo (Milan, IT), Motta; Gianni (Barlassina, IT), Sironi; Giorgio (Vignate, IT), Testa; Rodolfo (Vignate, IT) Assignee(s): Recordati, S.a., Chemical and Pharmaceutical Company (chiasso, Ch) Patent Number: 6,303,606 Date filed: May 5, 2000 Abstract: Described is the use in the treatment of either male or female sexual dysfunction of selective antagonists of the.alpha.sub.1B -adrenergic receptor and the pharmaceutical compositions containing them as compounds capable of helping the sexual act avoiding at the same time excessive side effects due to acute hypotension. Excerpt(s): This invention relates to the use in the treatment of human sexual dysfunction of selective antagonists of the.alpha.sub.1b -adrenergic receptor and to
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pharmaceutical compositions containing them as compounds for assisting the sexual act. Sexual dysfunction is the result of different mechanisms in males and females. In males impotence is defined as the inability to obtain an erection sufficient for intercourse. Erection is achieved as a result of blood inflow into the corpora cavernosa of the penis, which produces engorgement of the corpora cavernosa, and subsequent penile erection. It is estimated that as many as 30 million American men experience some degree of erectile dysfunction, the prevalence of which increases with age (Feldman et al., J. Urol. 151: 54-61, 1994). The causes of impotence can be divided into two subcategories: 1) organic and 2) psychological. The organic aspects of impotence are caused by underlying vascular disease such as that associated with hypertension, diabetes mellitus and prescription medications. About half of all cases of impotence are of vascular origin. Because the physiologic process of erection is initiated by an increase in blood flow through the penile arteries and shunting of blood into the vascular spaces of the corpora cavernosa, erectile dysfunction can result from the inability of the arteries of the penis to dilate, thereby inhibiting the flow of blood into the erectile tissue. Web site: http://www.delphion.com/details?pn=US06303606__
Patent Applications on Hypotension 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 hypotension: •
Angiopoietins and methods of use thereof Inventor(s): Kalish, Susan Croll; (Tarrytown, NY) Correspondence: Linda O. Palladino; Regeneron Pharmaceuticals, INC.; 777 Old Saw Mill River Road; Tarrytown; NY; 10591; US Patent Application Number: 20030082177 Date filed: October 18, 2002 Abstract: The invention generally relates to angiogenic factors and more particularly to the angiopoietin family of growth factors and to methods of using these growth factors to induce vasodilation and hypotension and reducing hypertension. Excerpt(s): This application claims priority of U.S. Provisional Application No. 60/348,415, filed Oct. 25, 2001. Throughout this application various patents and other publications are referenced. The disclosures of each and all of these patents and other publications in their entireties are hereby incorporated by reference into this application. The invention generally relates to angiogenic factors and more particularly to the angiopoietin family of growth factors and to methods of using these growth factors to induce vasodilation. Hypertension is a condition that occurs when the blood pressure inside the large arteries is too high. Hypertension is very common, affecting about 50 million people in the United States alone. It is more common as people grow older and is both more common and more serious in African Americans. Most cases of hypertension are of unknown etiology. It is known that the tendency to develop hypertension can be inherited. Environment also plays a very important role in
10
This has been a common practice outside the United States prior to December 2000.
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hypertension. For example, hypertension may be avoided by keeping body weight under control, keeping physically fit, eating a healthy diet, limiting alcohol intake, and avoiding medications that might increase blood pressure. Other less common causes of hypertension include disorders of the kidneys or endocrine glands. Hypertension has been called "the silent killer" because it has no specific symptoms and yet can lead to death. People with untreated hypertension are much more likely to die from or be disabled by cardiovascular complications such as strokes, heart attacks, heart failure, heart rhythm irregularities, and kidney failure, than people who have normal blood pressure. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Benzimidazole derivatives Inventor(s): Itoh, Satoru; (Tsukuba-shi, JP), Kato, Tetsuya; (Tsukuba-shi, JP), Kawamoto, Hiroshi; (Tsukuba-shi, JP), Kobayashi, Kensuke; (Tsukuba-shi, JP), Okamoto, Osamu; (Tsukuba-shi, JP), Takahashi, Hirobumi; (Tsukuba-shi, JP), Yoshizumi, Takashi; (Tsukuba-shi, JP) Correspondence: Wenderoth, Lind & Ponack, L.L.P.; 2033 K Street N. W.; Suite 800; Washington; DC; 20006-1021; US Patent Application Number: 20030236267 Date filed: May 14, 2003 Abstract: This invention provides compounds which are represented by a general formula [I] 1[in which X stands for hydrogen or halogen; B stands for halogen, cyano or optionally fluorine-substituted lower alkyl; D stands for a 3-10 membered aliphatic nitrogen-containing heterocyclic group; R.sup.3, R.sup.4 and R.sup.5 may be same or different, and each stands for hydrogen, lower alkyl optionally having substituent group(s) and the like; and a is 0 or 1]. These compounds exhibit high affinity to nociceptin receptors and whereby inhibit actions of nociceptin, and are useful as an analgesic, antiobestic, agent for ameliorating brain function, treating agents for Alzheimer's disease and dementia, and therapeutic agents for schizophrenia, neurodegenerative diseases, depression, diabetes insipidus, polyuria, hypotension and the like. Excerpt(s): This invention relates to novel benzimidazole derivatives. These compounds exhibit an antagonism to binding of nociceptin to nociceptin receptor ORL1 (Opioid receptor-like-1 receptor) and are useful as an analgesic against diseases accompanied with pain such as cancerous pain, postoperative pain, migraine, gout, chronic rheumatism, chronic pain and neuralgia; a reliever against tolerance to narcotic analgesic represented by morphine; a reliever against dependence on narcotic analgesic represented by morphine or against addiction; an analgesic enhancer; an antiobestic or appetite suppressor; a treating or prophylactic agent for cognitive impairment and dementia/amnesia in aging, cerebrovascular diseases and Alzheimer's disease; an agent for treating developmental cognitive abnormality in attention deficit, hyperactivity disorder and learning disability; a remedy for schizophrenia; an agent for treating neurodegenerative diseases represented by Parkinsonism and chorea; an antidepressant or treating agent for affective disorder; a treating or prophylactic agent for diabetes insipidus; a treating or prophylactic agent for polyuria; a remedy for hypotension, and the like. Nociceptin (the same substance as orphanin FQ) is a peptide comprising 17 amino acid units having a similar structure to that of opioid peptide. Nociceptin has an augmenting activity on reaction against nociceptive stimulation, an
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appetite stimulating activity, an activity for reducing a space learning ability, an antagonism against an analgesic action of classic opiate agonists, a dopamine release inhibitory action, a water diuresis action, a vasodilative action and a systemic blood pressure-lowering action, and it is considered to take part in intracerebral controlling of pain, appetite and memory learning through a nociceptin receptor ORL1 [cf. Nature, 377, 532 (1995); Society for Neuroscience, 22, 455 (1996); NeuroReport, 8, 423 (1997); Eur. J. Neuroscience, 9, 194 (1997); Neuroscience, 75, 1 (1996); ibid., 333; Life Sciences, 60, PL15 (1997); ibid., PL141; Proceedings for National Academy of Sciences, 94, 14858 (1997)]. Further, it is known that morphine tolerance is reduced or memory and learning ability are improved in knockout mice in which expression of nociceptin receptor ORL1 is inhibited [cf. Neuroscience Letters, 237, 136 (1997)]; Nature, 394, 577 (1998)]. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Benzimidazole derivatives Inventor(s): Itoh, Satoru; (Tsukuba-shi, JP), Iwasawa, Yoshikazu; (Tsukuba-shi, JP), Kato, Tetsuya; (Tsukuba-shi, JP), Kawamoto, Hiroshi; (Tsukuba-shi, JP), Kobayashi, Kensuke; (Tsukuba-shi, JP), Okamoto, Osamu; (Tsukuba-shi, JP), Yamamoto, Izumi; (Tsukuba-shi, JP) Correspondence: Wenderoth, Lind & Ponack, L.L.P.; 2033 K Street N. W.; Suite 800; Washington; DC; 20006-1021; US Patent Application Number: 20040044056 Date filed: May 15, 2003 Abstract: This invention relates to the compounds represented by a general formula [I]: 1[in which A.sup.1 and A.sup.2 represent optionally fluorine-substituted methine or the like; B represents halogen, cyano, lower alkyl or the like; D represents optionally substituted heterocyclic group or the like; and G represents C.sub.3-C.sub.20 aliphatic group such as alicyclic group]. These compounds inhibit nociceptin activities due to their high affinity to nociceptin receptor, and are useful as analgesic, antiobestic, corebral function improver, drugs for treatment of alzheimer's disease and dementia, remedies for schizophrenia and neurodegenerative diseases, antidepressant, remedies for diabetes insipidus, polyuria, hypotension and so on. Excerpt(s): This invention relates to benzimidazole derivatives which are useful in the field of pharmaceuticals. These benzimidazole derivatives exhibit an action of inhibiting binding of nociceptin to nociseptin receptor ORL1 (Opioid receptor like-1 receptor) and are useful as an analgesic, a reliever against tolerance to narcotic analgesic represented by morphine, a reliever against dependence on narcotic analgesic represented by morphine, an analgesic enhancer, an antiobestic, a drug for ameliorating brain function, a drug for treating Alzheimer's disease, an anti-dementia drug, a remedy for schizophrenia, a drug for treating regressive neurodegenerative diseases represented by Parkinsonism and chorea, an antidepressant, a remedy for diabetes insipidus, a remedy for polyuria, or a remedy for hypotension. Nociceptin (the same substance as orphanin FQ) is a peptide comprising 17 amino acids and having a similar structure to that of opioid peptide. Nociceptin has an augmenting activity on reaction against nociceptive stimulation, an appetite stimulating activity, an activity for reducing a space learning ability, an antagonism against an analgesic action of classic opiate agonists, a dopamine release inhibitory action, a water diuresis action, a vasodilative action and a systemic blood pressure-lowering action, and it is considered to take part in controlling pain, appetite and memory learning through a nociceptin receptor ORL1 [refer to Nature, vol.
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377, p. 532 (1995); Society for Neuroscience, vol. 22, p. 455 (1996); NeuroReport, vol. 8, p. 423 (1997); Eur. J. Neuroscience, vol. 9, p. 194 (1997); Neuroscience, vol. 75, pp. 1 and 333 (1996); and Life Science, vol. 60, pp. PL15 and PL141 (1997)]. Further, it is known that morphine tolerance is reduced or memory and learning ability are improved in knockout mice in which expression of nociceptin receptor ORL1 is inhibited [Neuroscience Letters, vol. 237, p. 136 (1997)]; Nature, vol. 394, p. 577 (1998)]. Therefore, substances which specifically inhibit binding of nociceptin to nociceptin receptor ORL1 are useful as an analgesic against diseases accompanied with pain such as cancerous pain, postoperative pain, migraine, gout, chronic rheumatism, chronic pain and neuralgia; a reliever against tolerance to narcotic analgesic represented by morphine, a reliever against dependence on narcotic analgesic represented by morphine, an analgesic enhancer, an antiobestic, a drug for ameliorating brain function, a prophylactic for Alzheimer's disease, a drug for treating Alzheimer's disease, a prophylactic for dementia, an anti-dementia drug, a remedy for schizophrenia, a drug for treating regressive neurodegenerative diseases represented by Parkinsonism and chorea, an antidepressant, a remedy for diabetes insipidus, a remedy for polyuria or a remedy for hypotension. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Cardiac rhythm management system for hypotension Inventor(s): Daum, Douglas R.; (Oakdale, MN), Scheiner, Avram; (Vadnais Heights, MN) Correspondence: Schwegman, Lundberg, Woessner & Kluth, P.A.; P.O. Box 2938; Minneapolis; MN; 55402; US Patent Application Number: 20020147475 Date filed: April 10, 2001 Abstract: A cardiac rhythm management system detects hypotension based on a measurement of thoracic impedance. It also provides therapy to treat the hypotension. Excerpt(s): The present system relates generally to cardiac rhythm management systems and particularly, but not by way of limitation, to a such a system for hypotension. When functioning properly, the human heart maintains its own intrinsic rhythm, and is capable of pumping adequate blood throughout the body's circulatory system. However, some people have irregular cardiac rhythms, referred to as cardiac arrhythmias. Such arrhythmias result in diminished blood circulation. One mode of treating cardiac arrhythmias uses drug therapy. Drugs are often effective at restoring normal heart rhythms. However, drug therapy is not always effective for treating arrhythmias of certain patients. For such patients, an alternative mode of treatment is needed. One such alternative mode of treatment includes the use of a cardiac rhythm management system. Such systems are often implanted in the patient and deliver therapy to the heart. Cardiac rhythm management systems include, among other things, pacemakers, also referred to as pacers. Pacers deliver timed sequences of low energy electrical stimuli, called pace pulses, to the heart, such as via an intravascular leadwire or catheter (referred to as a "lead") having one or more electrodes disposed in or about the heart. Heart contractions are initiated in response to such pace pulses (this is referred to as "capturing" the heart). By properly timing the delivery of pace pulses, the heart can be induced to contract in proper rhythm, greatly improving its efficiency as a pump. Pacers are often used to treat patients with bradyarrhythmias, that is, hearts that beat too slowly, or irregularly. Such pacers coordinate atrial and ventricular contractions
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to improve pumping efficiency. Cardiac rhythm management systems also include coordination devices for coordinating the contractions of both the right and left sides of the heart for improved pumping efficiency. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Catecholamine pharmaceutical compositions and methods Inventor(s): Dillon, Patrick F.; (East Lansing, MI), Root-Bernstein, Robert S.; (East Lansing, MI) Correspondence: Harness, Dickey & Pierce, P.L.C.; P.O. Box 828; Bloomfield Hills; MI; 48303; US Patent Application Number: 20030216413 Date filed: March 28, 2003 Abstract: Pharmaceutical compositions and method using adrenergic compounds and complement compounds. Compositions are provided comprising:(c) a subefficacious amount of an adrenergic compound; and(d) a safe and effective amount of a complement to the adrenergic compound.Methods are also provided comprising the administration of:(c) a low dose of an adrenergic compound; and(d) a safe and effective amount of a complement to said adrenergic compound.Preferably, the adrenergic compound is a catecholamine. Complements include ascorbates, opioids, polycarboxylic acid chelaters, and mixtures thereof. Preferred complements include ascorbates, particularly ascorbic acid. Methods include the treatment of neurological disorders, hypotension, forward failure, backward failure, congestive heart failure, shock, hypertension, hemorrhage, disorders associated with anesthesia, chronic obstructive pulmonary disease, asthma, colic, Crohn's disease, anaphylaxis, interstitial cystitis, overactive bladder syndrome, premature labor, myethsenia gravis, and glaucoma. Excerpt(s): This application is a continuation-in-part of International Application PCT/US01/30272, with an international filing date of Sep. 27, 2001, published in English under PCT Article 21(2), which claims the benefit of U.S. Provisional Application No. 60/236,751, filed Sep. 29, 2000. This invention relates to novel methods of treating disorders mediated by adrenergic receptors, and novel pharmaceutical compositions containing catecholamines or other adrenergic compounds. For example, the compositions and methods of this invention comprise the use of catecholamines and ascorbates in the treatment of a variety of disorders, including asthma, hypertension, and congestive heart failure. Catecholamines and related adrenergic (sympathomimetic) drugs are involved in the regulation of a wide variety of body functions. Such compounds have their effect directly or indirectly on the alpha- and beta-adrenergic receptors found in tissues throughout the body. Because the functions that are mediated by these receptors are diverse, agents that agonize or antagonize their activity are useful in the treatment of a variety of clinical disorders. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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cDNA clone MY1 that encodes a novel human 7-transmembrane receptor Inventor(s): Yanagisawa, Masashi; (Dallas, TX) Correspondence: Glaxosmithkline; Corporate Intellectual Property - Uw2220; P.O. Box 1539; King OF Prussia; PA; 19406-0939; US Patent Application Number: 20030083466 Date filed: October 28, 2002 Abstract: MY1 polypeptides and polynucleotides and methods for producing such polypeptides by recombinant techniques are disclosed. Also disclosed are methods for utilizing MY1 polypeptides and polynucleotides in the design of protocols for the treatment of infections such as bacterial, fungal, protozoan and viral infections, particularly infections caused by HIV-1 or HIV-2; pain; cancers; anorexia nervosa; bulimia; cachexia; obesity; diabetes; asthma; Parkinson's disease; acute heart failure; hypotension; hypertension; urinary retention; osteoporosis; angina pectoris; myocardial infarction; ulcers; asthma; allergies; benign prostatic hypertrophy; and psychotic and neurological disorders, including anxiety, schizophrenia, manic depression, delirium, dementia, severe mental retardation and dyskinesias, such as Huntington's disease or Gilles dela Tourett's syndrome, among others, and diagnostic assays for such conditions. Excerpt(s): This invention relates to newly identified polynucleotides, polypeptides encoded by them and to the use of such polynucleotides and polypeptides, and to their production. More particularly, the polynucleotides and polypeptides of the present invention relate to G-protein coupled receptor family, hereinafter referred to as MY1. The invention also relates to inhibiting or activating the action of such polynucleotides and polypeptides. It is well established that many medically significant biological processes are mediated by proteins participating in signal transduction pathways that involve G-proteins and/or second messengers, e.g., cAMP (Lefkowitz, Nature, 1991, 351:353-354). Herein, these proteins are referred to as proteins participating in pathways with G-proteins or PPG proteins. Some examples of these proteins include the GPC receptors, such as those for adrenergic agents and dopamine (Kobilka, B. K., et al., Proc. Natl Acad. Sci., USA, 1987, 84:46-50; Kobilka, B. K., et al., Science, 1987, 238:650-656; Bunzow, J. R., et al., Nature, 1988, 336:783-787), G-proteins themselves, effector proteins, e.g., phospholipase C, adenyl cyclase, and phosphodiesterase, and actuator proteins, e.g., protein kinase A and protein kinase C (Simon, M. I., et al., Science, 1991, 252:802-8). For example, in one form of signal transduction, the effect of hormone binding is activation of the enzyme, adenylate cyclase, inside the cell. Enzyme activation by hormones is dependent on the presence of the nucleotide GTP. GTP also influences hormone binding. A G-protein connects the hormone receptor to adenylate cyclase. Gprotein was shown to exchange GTP for bound GDP when activated by a hormone receptor. The GTP-carrying form then binds to activated adenylate cyclase. Hydrolysis of GTP to GDP, catalyzed by the G-protein itself, returns the G-protein to its basal, inactive form. Thus, the G-protein serves a dual role, as an intermediate that relays the signal from receptor to effector, and as a clock that controls the duration of the signal. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Feedback control of ultrafiltration to prevent hypotension Inventor(s): Gelfand, Mark; (New York, NY), Levin, Howard R.; (Teaneck, NJ), O'Mahony, John; (Hackensack, NJ) Correspondence: Nixon & Vanderhye P.C.; 1100 North Glebe RD., 8th Floor; Arlington; VA; 22201; US Patent Application Number: 20020085951 Date filed: December 29, 2000 Abstract: A method and system for the extracorporeal treatment of blood to remove fluid from the fluid overloaded patient is disclosed that non-invasively measures an oxygen level in the venous blood. The oxygen blood level is used to detect when hypotension is about to occur in a patient. The oxygen level measurements are used as feedback signals. These feedback signals are applied to automatically control the rate of fluid extraction to achieve the desired clinical outcome and avoid precipitating a hypotensive crisis in the patient. Excerpt(s): The present invention relates to an apparatus for the extracorporeal treatment of blood and more specifically to the automatic control of fluid removal from the blood of patients suffering from fluid overload and averting therapy induced hypotension. Renal Replacement Therapy (RRT) has evolved from the long, slow hemodialysis treatment regime of the 1960's to a diverse set of therapy options, the vast majority of which employ high permeability membrane devices and ultrafiltration control systems. Biologic kidneys remove metabolic waste products, other toxins, and excess water. They also maintain electrolyte balance and produce several hormones for a human or other mammalian body. An artificial kidney, also called a hemodialyzer or dialyzer, and attendant equipment and supplies are designed to replace the bloodcleansing functions of the biologic kidney. At the center of artificial kidney design is a semipermeable filter membrane that allows passage of water, electrolytes, and solute toxins to be removed from the blood. The membrane retains in the blood, the blood cells, plasma proteins and other larger elements of the blood. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Human endothelin-bombesin receptor Inventor(s): Kumar, Chandrika; (West Windsor, NJ), Li, Yi; (Sunnyvale, CA), Rosen, Craig A.; (Laytonsville, MD) Correspondence: Human Genome Sciences Inc; 9410 Key West Avenue; Rockville; MD; 20850 Patent Application Number: 20030109676 Date filed: November 13, 2002 Abstract: A human endothelin-bombesin receptor polypeptide and DNA (RNA) encoding such polypeptide and a procedure for producing such polypeptide by recombinant techniques is disclosed. Also disclosed are methods for utilizing such polypeptide for identifying agonists and antagonists to such polypeptide. Agonists to the endothelin-bombesin receptor polypeptide of the present invention may be used to treat asthma, Parkinson's Disease, acute heart failure, hypotension and osteoporosis. Antagonists against such polypeptides may be used therapeutically to treat hypertension, ulcerigenesis, subarachnoid hemorrhage, asthma, tumors, ciclosporin
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toxicity, cancer and septic shock. Also disclosed are diagnostic methods for detecting mutations in the polynucleotides of the present invention and for detecting levels of the soluble polypeptides in samples derived from a host. Excerpt(s): This application is a divisional of application Ser. No. 09/520,210, filed Mar. 7, 2000, which is a divisional of application Ser. No. 09/030,970, filed on Feb. 26, 1998, now U.S. Pat. No. 6,143,519, issued on Nov. 7, 2000, which is a divisional of application Ser. No. 08/465,687, filed on Jun. 6, 1995, now U.S. Pat. No. 5,750,370, issued on May 12, 1998, which is a continuation-in-part of International Application No. PCT/US94/11843, filed Oct. 17, 1994; priority to these applications is hereby claimed under 35 U.S.C.sctn. 120, and each of these applications is hereby incorporated by reference in its entirety. This invention relates to newly identified polynucleotides, polypeptides encoded by such polynucleotides, the use of such polynucleotides and polypeptides, as well as the production of such polynucleotides and polypeptides. More particularly, the polypeptide of the present invention is a human 7-transmembrane receptor. The transmembrane receptor is a G-protein coupled receptor. More particularly, the 7transmembrane receptor has been putatively identified as an endothelin-bombesin receptor, sometimes hereinafter referred to as "ETBR." The invention also relates to inhibiting the action of such polypeptides. It is well established that many medically significant biological processes are mediated by proteins participating in signal transduction pathways that involve G-proteins and/or second messengers, e.g., cAMP (Lefkowitz, Nature, 351:353-354 (1991)). Herein these proteins are referred to as proteins participating in pathways with G-proteins or PPG proteins. Some examples of these proteins include the GPC receptors, such as those for adrenergic agents and dopamine (Kobilka, B. K., et al., PNAS, 84:46-50 (1987); Kobilka, B. K., et al., Science, 238:650-656 (1987); Bunzow, J. R., et al., Nature, 336:783-787 (1988)), G-proteins themselves, effector proteins, e.g., phospholipase C, adenyl cyclase, and phosphodiesterase, and actuator proteins, e.g., protein kinase A and protein kinase C (Simon, M. I., et al., Science, 252:802-8 (1991)). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Human vanilloid receptor-like proteins Inventor(s): Shinjo, Katsuhiro; (Chita-gun, JP), Yabuuchi, Hikaru; (Yokohama, JP) Correspondence: Gregg C. Benson; Pfizer INC.; Patent Department, MS 4159; Eastern Point Road; Groton; CT; 06340; US Patent Application Number: 20030017527 Date filed: May 30, 2001 Abstract: This invention relates to human vanilloid receptor-like protein 2 (VRL-2) polypeptides, polynucleotides encoding such polypeptides, polynucleotide probes or primers, expression vectors and host cells comprising such DNA molecules. This invention further relates to a process for producing the polypeptides; an antibody immunospecific for the polypeptide; a diagnostic kit for diagnosing the VRL-2 receptor related disease; a method for screening to identify modulators which modulate the polypeptides; modulators identified by the screening method; a pharmaceutical composition for treatment of conditions associated with biological function of the polypeptides; and a non-human transgenic animal model for vanilloid receptor-like gene. The polypeptides and the DNA molecules of the present invention can be used to identify agonists, antagonists or the like. These agonists and antagonists are useful for treatment of diseases such as pain, nociceptive pain, chronic pain, neuropathic pain,
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postoperative pain, cancer pain, rheumatoid arthritic pain, osteoarthritis, diabetic neuropathies, neuralgia, neuropathies, algesia, nerve injury, muscle-skeletal pain, low back pain, neurodegeneration, stroke, inflammatory disorders, athma, allergy, urogenital disorders, incontinence, hypertension, hypotension, perivasular disease and the like. Excerpt(s): The analgesic properties of capsaicin and capsaicinoides are known for their uses in the treatment of a variety of disorders such as pain, chronic pain, neuropathic pain, postoperative pain, rheumatoid arthritic pain, neuralgia, neuropathies, algesia, nerve injury, ischaemia, neurodegeneration stroke incontinence and inflammatory disorders (e.g., Campbell et al. "Clinical Applications of Capsaicin and Its Analogues" in Capsaicin in the Study of Pain, Academic Press pgs. 255-272 (1993)). Capsaicin receptors are believed to be members of the ion channel family of polypeptides. These receptors are believed to be associated with the mechanism of action of capsaicin (a vanilloid compound). Capsaicin elicits a senstation of burning pain by selectively activating sensory neurons that convey information about noxious stimuli to the central nervous system (e.g, Caterina, M. J. eta al., "The Capsaicin Receptor: A Heat Activated Ion Channel In the Pain Pathway", Nature 389, 816-824 (1997) and Caterina, M. J. et al., "A Capsaicin-Receptor Homologue with A High Threshold For Noxious Heat", Nature 398, 436-441 (1999)). The channels are permeable to cations and exhibit a notable preferance for divalent cations, particularly calcium ions. The level of calcium ion permeability exceeds that observed for most non-selective cation channels and is similar to values observed for NMDA-type glutamate receptors and alpha-7 nicotinic acetylcholine receptors. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Hypotension Inventor(s): Eckhart, Andrea D.; (Durham, NC), Koch, Walter J.; (Durham, NC) Correspondence: Nixon & Vanderhye P.C.; 8th Floor; 1100 North Glebe Road; Arlington; VA; 22201; US Patent Application Number: 20020165118 Date filed: October 31, 2001 Excerpt(s): This application claims priority from Provisional Application No. 60/244,210, filed Oct. 31, 2000, the entire content of which is incorporated herein by reference. The present invention relates, in general, to hypotension and, in particular, to a novel therapeutic target for lowering blood pressure. High blood pressure or hypertension is a prevalent disease in the United States and is a leading cause of morbidity and mortality. Understanding the mechanisms that lead to hypertension is critical to improve existing health care for this disorder. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Method for diagnosis of chronic headache Inventor(s): Almazov, Irina G.; (Kfar Saba, IL) Correspondence: DR. Mark Friedman Ltd; C/o Bill Polkinghorn - Discovery Dispatch; 9003 Florin Way; Upper Marlboro; MD; 20772; US Patent Application Number: 20020179095 Date filed: May 29, 2001 Abstract: A method for determining a cause of chronic headache is disclosed. The method includes: (a) determining whether the headache of a person is postural, (b) determining whether the person has meningeal irritation, and (c) determining that the headache is caused by intracranial hypotension if the headache is postural and the person has meningeal irritation. Excerpt(s): The present invention relates to clinical medical diagnosis and, more particularly, to a method for determining a cause of chronic headache. Headache is felt to be the most common human malady and the most prevalent neurologic symptom associated with any disease. Without question, the most frequent of all the painful states that afflict humans, it rivals backache as the most common reason for medical consultation. It accounts for almost 20 million outpatient visits a year in the United States. and is a leading cause for the use of over-the-counter medications. Headache is a major social and economic burden for society. In children, headache is an extremely common complaint. Depending on the etiology, frequency and intensity of the headache, headaches can have a major effect on a child's school attendance and academic performance, as well as the child's memory, personality and interpersonal relationships. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Method of treating anemia Inventor(s): Creasy, Caretha; (Erdenheim, PA), Dillon, Susan B.; (Chester Springs, PA), Lord, Kenneth A.; (Collegeville, PA) Correspondence: Ratner & Prestia; P.O. Box 980; Valley Forge; PA; 19482-0980; US Patent Application Number: 20030176375 Date filed: May 14, 2001 Abstract: hYAK3-2 polypeptides and polynucleotides and methods for producing such polypeptides by recombinant techniques are disclosed. Also disclosed are methods for utilizing hYAK3-2 polypeptides and polynucleotides in the design of protocols for the treatment of bone loss including osteoporosis; inflammatory diseases such as Adult Respiratory Disease Syndrome (ARDS), Rheumatoid arthritis, Osteoarthritis, Inflammatory Bowel Disease (IBD), psoriasis, dermatitis, asthma, allergies; infections such as bacterial, fungal, protozoan and viral infections, particularly infections caused by HIV-1 or HIV-2; HIV-associated cachexia and other immunodeficiency disorders; septic shock; pain; injury; cancers including testicular cancer; anorexia; bulimia; neutropenia; cytopenia; anemias, including anemias due to renal insufficiency or to chronic disease, such as autoimmunity or cancer, and drug-induced anemias; polycythemia; myelosuppression; Parkinson's disease; cardiovascular disease including restenosis, atherosclerosis, acute heart failure, myocardial infarction; hypotension; hypertension; urinary retention; angina pectoris; ulcers; benign prostatic hypertrophy;
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and psychotic and neurological disorders, including anxiety, schizophrenia, manic depression, delirium, dementia, severe mental retardation and dyskinesias, such as Huntington's disease or Gilles dela Tourett's syndrome., among others, and diagnostic assays for such conditions. Excerpt(s): This application claims priority to U.S. Ser. No. 60/118,045 filed Feb. 1, 1999, which is incorporated by reference in its entirety. This invention relates to newly identified polynucleotides, polypeptides encoded by them and to the use of such polynucleotides and polypeptides, and to their production. More particularly, the polynucleotides and polypeptides of the present invention relate to a serine/threonine protein kinase, hereinafter referred to as hYAK3-2. The invention also relates to inhibiting or activating the action of such polynucleotides and polypeptides. A number of polypeptide growth factors and hormones mediate their cellular effects through a signal transduction pathway. Transduction of signals from the cell surface receptors for these ligands to intracellular effectors frequently involves phosphorylation or dephosphorylation of specific protein substrates by regulatory protein serine/threonine kinases (PSTK) and phosphatases. Serine/threonine phosphorylation is a major mediator of signal transduction in multicellular organisms. Receptor-bound, membranebound and intracellular PSTKs regulate cell proliferation, cell differentiation and signalling processes in many cell types. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Model systems for neuordegenerative and cardiovascular disorders Inventor(s): Perez, Dianne M.; (Broadview Heights, OH), Zuscik, Michael J.; (Westlake, OH) Correspondence: Calfee Halter & Griswold, Llp; 800 Superior Avenue; Suite 1400; Cleveland; OH; 44114; US Patent Application Number: 20020133832 Date filed: January 18, 2002 Abstract: New tools for determining the role the.alpha.sub.1B adrenergic receptor plays in the physiology and pathology of the brain and the cardiovascular system are provided The tools are transgenic non-human mammalian animals, particularly transgenic mice, that have integrated into the genomes of their somatic cells a transgene encoding an exogenous, wild-type.alpha.1B adrenergic receptor or a variant thereof. The transgenic animals of the present invention exhibit phenotypical symptoms similar to those exhibited by individuals with neurodegenerative diseases, particularly Parkinson's disease or epilepsy. Such mammals also exhibit phenotypical symptoms similar to individuals with cardiovascular diseases such as hypertrophy of the heart and hypotension. Accordingly, these transgenic mammals are also useful for screening for drugs that ameliorate these cardiovascular conditions. Also provided is a method of determining the ability of a test agent or compound to modulate or block function of the.alpha.sub.1B adrenergic receptor. The method comprises administering the test agent to a transgenic non-human animal which is expressing a constitutively active form of the.alpha.sub.1B receptor, or elevated levels of the wild-type.alpha.sub.1B receptor on the cell surface of various organs, and then assaying for changes in.alpha.sub.1B receptor function. The present invention also relates to methods for treating neurodegenerative disorders in a subject, particularly neurodegenerative disorders evidenced by abnormal locomoter activity or seizures. In one embodiment, the method
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comprises administering a pharmaceutical composition comprising a biologically effective amount of an.alpha.sub.1 adrenergic receptor antagonist to the subject. Excerpt(s): The adrenergic receptor family is a group of heptahelical G protein-coupled receptors that mediate the effects of the sympathetic nervous system. At present, this family is known to contain three.alpha.1, three.alpha.2, and three B receptor subtypes. All of the receptors in this family bind to and are activated by the hormones epinephrine and norepinephrine. By a series of steps involving G proteins, the activated receptors then activate an effector. In the case of the.alpha.sub.1A adrenergic receptors the effector is phospholipase C; in the case of the.alpha.sub.2 and.beta., the effector is adenylate cyclase. Cells expressing.alpha.sub.1-adrenergic receptors are found in the heart, liver, kidney, brain and spleen. Surprisingly, such cells do not express a single subtype. Indeed, in the brain, all three.alpha.1 subtypes co-exist on a single cell. Attempts have been made to elucidate the specific role each.alpha.1 receptor plays in the physiology and pathophysiology of such cells using agonists or antagonists which bind with greater affinity to one of the oil receptors. However, the antagonists that are currently available do not have sufficient selectivity to discriminate between the subtypes. Moreover, such studies typically involve a single bolus injection of the respective agonist or antagonist, and, therefore, cannot identify the pathologies that result from chronic activation of a single receptor subtype. Accordingly, it is desirable to have new tools and methods which can be used to determine the effect of chronic activation of a single.alpha.sub.1 adrenergic receptor subtype. A tool which can be used to screen for antagonists for a particular.alpha.sub.1 adrenergic receptor and to determine the systemic side effects of such antagonists is especially desirable. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Novel alicyclic imidazoles as H3 agents Inventor(s): Jiang, Jack B.; (Orange Village, OH), Rong, Yajing; (Monmonth Jct, NJ), Syed, Ali M.; (Solon, OH) Correspondence: Rockey, Milnamow & Katz, LTD.; Two Prudential Plaza, STE. 4700; 180 North Stetson Avenue; Chicago; IL; 60601; US Patent Application Number: 20020042400 Date filed: August 15, 2001 Abstract: Alicyclic imidazole compounds; pharmaceutically active compositions containing such compounds; and the use of such compounds in formulations for the control or prevention of disease states in which histamine H.sub.3 receptors are involved, such as allergy, inflammation, hypotension, glaucoma, sleeping disorders, states of hyper- and hypo-motility of the gastro-intestinal tract, cardiovascular disease, hypo- and hyper-activity of the central nervous system, Alzheimer's, schizophrenia, obesity and migraines are disclosed. Excerpt(s): The present invention is directed to alicyclic imidazoles which interact with the histamine H.sub.3 receptor as agonists, antagonists or inverse agonists; pharmaceutically active compositions containing such compounds; and the use of such compounds in formulations for the control or prevention of disease states in which histamine H.sub.3 receptors are involved, such as allergy, inflammation, hypotension, glaucoma, sleeping disorders, states of hyper- and hypo-motility of the gastro-intestinal tract, cardiovascular disease, hypo- and hyper-activity of the central nervous system, Alzheimer's, schizophrenia, obesity and migraines. Histamine plays a role in regulating
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attentiveness and cognition in the central nervous system (CNS), and histamine levels in the brain are controlled by the histamine H.sub.3 receptor. Moreover, serotonin, norepinephrine, dopamine and acetylcholine all have been demonstrated to be regulated by the histamine H.sub.3 receptor. These neurotransmitters are known to play a role in many CNS psychiatric disorders involving higher cognitive function and/or emotion. Consequently, compounds affecting H.sub.3 receptor function (as agonists, antagonists or inverse agonists) could have utility in the treatment of a variety of CNS maladies, including but not limited to dementias, attention deficit hyperactivity disorder, depression, anxiety and schizophrenia. Histamine is also involved in the control of sleep/wake states and appetite. Accordingly, histamine H.sub.3 receptor ligands might be expected to be useful in treating insomnia, narcolepsy, age-related sleep disorders, obesity and anorexia. Although they exist in low density outside of the brain, histamine H.sub.3 receptors are found on the sympathetic and parasympathetic nerve terminals in the periphery, including the vasculature and heart. Thus, compounds that alter histamine H.sub.3 receptor activity might also have clinical utility in treating conditions such as migraine and cardiac dysfunction. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Pacing mode to reduce effects of orthostatic hypotension and syncope Inventor(s): Bornzin, Gene A.; (Simi Valley, CA), Kroll, Mark W.; (Simi Valley, CA), Sorensen, Chris; (Valencia, CA) Correspondence: Pacesetter Inc; 15900 Valley View Court; Sylmar; CA; 91392-9221; US Patent Application Number: 20030045910 Date filed: September 5, 2001 Abstract: An implantable cardiac stimulation device is programmed to administer pacing therapy in response to a change in a patient's position and a drop in blood pressure. The stimulation device is equipped with a position sensor to sense a position parameter indicative of when a patient changes from a supine position to an upright position and a pressure sensor to sense a pressure parameter indicative of a patient's blood pressure. The device administers cardiac pacing therapy to the patient based on both the position parameter and the pressure parameter. Excerpt(s): The present invention generally relates to methods and systems for providing cardiac pacing therapy. More particularly, the invention concerns methods and implantable stimulation devices to detect conditions that might give rise to orthostatic hypotension and/or syncope and provide pacing-based cardiac therapies aimed at reducing the effects of orthostatic hypotension and/or syncope. When an individual changes from a horizontal or supine position to a sitting or standing position, the cardiovascular system must make frequent and rapid adjustments to blood pressure and heart rate. When such adjustments are not accomplished, orthostatic hypotension occurs. Orthostasis means upright posture, and hypotension means low blood pressure. Thus, orthostatic hypotension describes the effects caused by low blood pressure when changing from a lying to upright position. Orthostatic hypotension is defined as a decrease of at least 20 mm Hg in systolic blood pressure when an individual moves from the supine to upright position. The symptoms of orthostatic hypotension include dizziness, faintness, or lightheadedness that appear when standing. Other symptoms that often accompany orthostatic hypotension include chest pain, trouble holding urine, impotence, and dry skin from loss of sweating. Some patients with severe orthostatic hypotension are severely incapacitated.
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Pharmaceutical kit comprising midodrine as active drug substance Inventor(s): Bertelsen, Poul; (Vanlose, DK), Mohr Olsen, Peder; (Kirke Hyllinge, DK), Skinhoj, Annette; (Rodovre, DK) Correspondence: Peter F. Corless, ESQ.; Dike, Bronsteins & Cushman; Edwards & Angell, Llp; P.O. Box 9169; Boston; MA; 02109; US Patent Application Number: 20020193445 Date filed: March 29, 2001 Abstract: Novel phannaceutcal kit comprising a controlled release pharmaceutical compositions for oral use containing midodrine and/or its active metabolite desglymidodrine and a relatively fast onset composition. The controlled release compositions are designed to release midodrine and/or desglymidodrine after oral intake in a manner which enables absorption to take place in the gastrointestinal tract so that a relatively fast peak plasma concentration of the active metabolite desglymidodrine is obtained followed by a prolonged and relatively constant plasma concentration of desglymidodrine.The controlled release compositions may be designed for administration once or twice daily, i.e. a therapeutically effective concentration of desglymidodrine is maintained for a period of at least 10-16 hours followed by a wash out period of about 8-12 hours in order to avoid the well-known midodrine related side effect with respect to supine hypertension. The therapeutically effective concentration of desglymidodrine is regarded as a plasma concentration of desglymidodrine of at least about 3 ng/ml. A composition is designed to release midodrine and/or desglymidodrine in at least the following consecutive steps; i) an initial relatively fast release of midodrine and/or desglymidodrine (in order to obtain a relatively fast onset of action), ii) a steady release or a slower release than in step 1 of midodrine and/or desglymidodrine (in order to maintain a plasma concentration of desglymidodrine which is prolonged and relatively constant), iii) a second rise in release of midodrine and/or desglymidodrine (in order to take advantage of absorption from the colon, i.e. such a second rise release is designed to take place when the composition (or the disintegrated parts of the composition) reaches the colon; normally this is regarded to take about 8 hours after oral intake, and iv) a decline in release rate corresponding to that essentially all midodrine and/or desgtymidodrine have been released from the composition.One of the advantages of the invention is that the controlled release composition provides a base line plasma concentration, which during most of the day is therapeutically effective. When a higher concentration is needed, only a minor supply of active drug substance is necessary to obtain a very fast relief from symptoms. If the constant base line plasma concentration was absent, it would be necessary to use a relative higher fast onset dose to reach the high therapeutically effective level. The kit according to the present invention is a superior tool for obtaining an optimal treatment with a minimum of active drug substance.Also disclosed is a method for treating orthostaic hypotension and/or urinary incontinence, the method comprising administration to a patient in need thereof of an effective amount of midodrine and/or desglymidodrine in a kit according to the invention. Excerpt(s): This application claims priority to U.S. Provisional Application No. 60/203.783, filed May 12, 2000 and is incorporated herein by reference. The present Invention relates to a method for treating mammals (such as, e.g., humans) in need thereof with a novel controlled release pharmaceutical composition for oral use
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containing midodrine and/or its active metabolite desglymidodrine together with a relatively fast onset composition of midodrine and/or its active metabolite desglymidodrine. The present invention also relates to a kit comprising a controlled release composition, e.g. intended for administration once or twice daily, together with one or more relatively fast onset compositions for supplemental and individual administration. The invention also relates to a pharmaceutical composition comprising comprising midodrine (ST 1085) or a pharmaceutically acceptable salt thereof and/or its active metabolite desglymidodrine (ST 1059) or a pharmaceutically acceptable salt thereof, the composition being adapted to provide midodrine and/or desglymidodrine in such a manner that a relatively fast therapeutically effective concentration of desglymidodrine is obtained after administration of the composition. 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
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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 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 •
Regulation of human g protein-coupled receptor Inventor(s): Kossida, Sophia; (Basel, CH) Correspondence: Banner & Witcoff; 1001 G Street N W; Suite 1100; Washington; DC; 20001; US Patent Application Number: 20040039170 Date filed: March 24, 2003 Abstract: Reagents which regulate human G protein-coupled receptor can play a role in preventing, ameliorating, or correcting dysfunctions or diseases including, but not limited to, infections such as bacterial, fungal, protozoan, and viral infections, particularly those caused by HIV viruses, cancers, anorexia, bulimia, asthma and other allergies, peripheral or central nervous system diseases such as Parkinson's disease, acute heart failure, hypotension, hypertension, urinary retention, osteoporosis, diabetes, angina pectoris, myocardial infarction, ulcers, inflammation, and benign prostatic hypertrophy. Excerpt(s): The invention relates to the area of G protein-coupled receptors. More particularly, it relates to the area of G protein-coupled receptors and their regulation. Many medically significant biological processes are mediated by signal transduction pathways that involve G proteins (Lefkowitz, Nature 351, 353-354, 1991). The family of G protein-coupled receptors (GPCR) includes receptors for hormones, neurotransmitters, growth factors, and viruses. Specific examples of GPCRs include receptors for such diverse agents as dopamine, calcitonin, adrenergic hormones, endothelin, cAMP, adenosine, acetylcholine, serotonin, histamine, thrombin, kinin, follicle stimulating hormone, opsins, endothelial differentiation gene-1, rhodopsins, odorants, cytomegalovirus, G proteins themselves, effector proteins such as phospholipase C, adenyl cyclase, and phosphodiesterase, and actuator proteins such as protein kinase A and protein kinase C. GPCRs possess seven conserved membranespanning domains connecting at least eight divergent hydrophilic loops. GPCRs (also known as 7TM receptors) have been characterized as including these seven conserved hydrophobic stretches of about 20 to 30 amino acids, connecting at least eight divergent hydrophilic loops. Most GPCRs have single conserved cysteine residues in each of the first two extracellular loops, which form disulfide bonds that are believed to stabilize
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functional protein structure. The seven transmembrane regions are designated as TM1, TM2, TM3, TM4, TM5, TM6, and TM7. TM3 has been implicated in signal transduction. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Thienopyranecarboxamide derivatives Inventor(s): Leonardi, Amedeo; (Milan, IT), Motta, Gianni; (Barlassina, IT), Riva, Carlo; (Varese, IT), Testa, Rodolfo; (Vignate, IT) Correspondence: Darby & Darby P.C.; 805 Third Avenue; New York; NY; 10022; US Patent Application Number: 20020193381 Date filed: August 16, 2001 Abstract: The invention is directed to compounds of Formula I: 1whereinR is an aryl, cycloalkyl or polyhaloalkyl group,R.sub.1 is chosen from the group consisting of alkyl, alkoxy, polyfluoroalkoxy, hydroxy and trifluoromethanesulfonyloxy; each of R.sub.2 and R.sub.3 independently is chosen from the group consisting of a hydrogen, halogen, alkoxy and polyfluoroalkoxy group, and n is 0, 1 or 2.The invention further provides pharmaceutical compositions comprising a compound of Formula I or a N-oxide or pharmaceutically acceptable salt of such a compound in admixture with a pharmaceutically acceptable diluent or carrier.In another aspect, the present invention is directed to methods for selectively preventing contractions of the urethra and lower urinary tract, without substantially affecting blood pressure, by administering one or more selected compounds of Formula I to a mammal (including a human) in need of such treatment in an amount or amounts effective for the particular use.In yet another aspect, the invention is directed to methods for blocking.alpha.sub.1 receptors, by delivering to the environment of said receptors, e.g., to the extracellular medium, (or by administering to a mammal possessing said receptors) an effective amount of a compound of the invention, in this way relieving diseases associated to overactivity of said receptors.It is also an object of the present invention to provide a method of treating BPH which avoids any undue side effects due to acute hypotension (i.e., limited effects on blood pressure).It is another object of the present invention to provide pharmaceutical compositions comprising 7-oxo-7H-thieno[3,2-b] pyran compounds which are selective.alpha.sub.1 adrenoceptor antagonists, which compositions are effective for the treatment of BPH optionally including a carrier or diluent.It is another object of the present invention to provide a method of treating BPH using 7-oxo-7Hthieno[3,2-b] pyran compounds which are selective.alpha.sub.1 adrenoceptor antagonists.Other aspects of the invention are the use of new compounds for lowering intraocular pressure, the treatment of cardiac arrhythmia and erectile dysfunction, treatment of sympathetically mediated pain, treatment of NLUTD, and treatment of LUTS in males and females.In another aspect of the invention, compounds of the invention are administered in combination with anticholinergic compounds. Excerpt(s): The enclosed application is based on Provisional Patent Application Seri al No. 60/179,423. Applicants claim the benefit of the filing date of the aforesaid Provisional Application under 35 U.S.C.sctn.119(e)(1). The present invention relates to thienopyranecarboxamide derivatives, to pharmaceutical compositions containing them and to uses for such derivatives and compositions. 7-Oxo-7H-thieno[3,2-b]pyran-3carboxylic acid and its N,.omega.-aminoalkylamides are compounds not yet reported in the literature. The present invention is directed to the new structural class of the N(substituted phenyl)-N'-[.psi.-(5-substituted-7-oxo-7H-thieno[3,2-b]pyran-3carbonylamino)alkyl]piperazines.
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Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Thromboxane ligands without blood clotting side effects Inventor(s): Burk, Robert M.; (Laguna Beach, CA), Krauss, Achim H-P; (Foothill Ranch, CA), Woodward, David F.; (Lake Forest, CA) Correspondence: Robert J. Baran (t2-7h); Allergan, INC.; 2525 Dupont Drive; Irvine; CA; 92612; US Patent Application Number: 20030109571 Date filed: August 5, 2002 Abstract: A method of treating ocular hypotension, hypertension, hemorrhage, myocardial ischemia, angina pectoris, coronary contraction, cerebrovascular contraction after subarachnoidal hemorrhage, cerebral hemorrhage and asthma which comprises administering to a mammal suffering therefrom a therapeutically effective amount of a thromboxane ligand which is a compound formula I, 1wherein Y is (CH.sub.2).sub.x; Z is selected from the group consisting of 2(CR.sub.2).sub.x, is an integer of 1 or 2; n is 0 or 1; R.sub.2 is hydrogen or an alkyl radical of from 1 to 4 carbons; A is an alkylene or alkenylene radical having from two to seven carbon atoms, which radical may be substituted with one or more hydroxy, oxo, alkyloxy or alkylcarboxy groups or said alkylene or alkenylene may have one or more enchained oxa or imino radicals; B is a methyl radical or a cycloalkyl radical having from three to seven carbon atoms, or an aryl radical, selected from the group consisting of hydrocarbyl aryl and heteroaryl radicals wherein the heteroatom is selected from the group consisting of nitrogen, oxygen and sulfur atoms, or substituted derivatives of said methyl, cycloalkyl or aryl radicals wherein said substituent is selected from the group consisting of halo, nitro, amino, thiol, hydroxy, alkyloxy and alkylcarboxy; and X is selected from the group consisting of nitro, cyano, --COOR, --CH.sub.2OR.sub.1, --C(O)N(R.sub.1).sub.2, -CH.sub.2N(R.sub.1).sub.2--CH.dbd.N--OH and --CH.sub.2SR.sub.1 radicals wherein R is a C.sub.1 to C.sub.10 alkyl, phenyl or benzyl and R.sub.1 is R or hydrogen; or a pharmaceutically acceptable salt thereof. Excerpt(s): This patent application is a continuation of U.S. patent Application Ser. No. 09/899,713 filed on Jul. 5, 2001, which is a continuation in part of U.S. patent application Ser. No. 09/334,356 filed on Jun. 16, 1999, now abandoned, which is a continuation of U.S. patent application Ser. No. 09/038,068 filed on Mar. 11, 1998, now abandoned, which is a continuation of U.S. patent application Ser. No. 08/832,431 filed on Apr. 2, 1997, now U.S. Pat. No. 5,741,812. which is a continuation in part of U.S. patent application Ser. No. 08/645,467, filed on May 13, 1996, now U.S. Pat. No. 5,650,431, which is a continuation in part of U.S. patent application Ser. No. 08/378,414, filed on Jan. 26, 1995, now U.S. Pat. No. 5,516,791, which is a divisional of U.S. patent application Ser. No. 08/174,534, which was filed on Dec. 28, 1993, now U.S. Pat. No. 5,416,106. The present invention relates to thromboxane receptor ligands including a carboxylic acid group derivative, which do not cause blood clotting. In particular, the thromboxane receptor ligands are bicyclic carboxylic acid derivatives wherein said bicyclic rings may be hydrocarbyl or oxohydrocarbyl, e.g. 7-[carboxyalkyl or alkenyl]-6-[alkyl or alkenyl]3-oxo-2,4-dioxobicyclo[3.2.1] octanes and derivatives thereof. In particular, hydroxyl, nitro, amino, amido, azido, oxime, thiol, ether and thiol ether derivatives of said carboxylic acid group are contemplated. In particular, 7-[6-carboxy-2-hexenyl]-6-[3hydroxy-1-o- ctenyl] 3-oxo-2,4-dioxobicyclo-[3.2.1] octane derivatives are disclosed. These compounds are useful as thromboxane agonists and antagonists. These
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compounds are also useful as ocular hypotensives. Ocular hypotensive agents are useful in the treatment of a number of various ocular hypertensive conditions, such as postsurgical and post-laser trabeculectomy ocular hypertensive episodes, glaucoma, and as presurgical adjuncts. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Treatment of septic shock Inventor(s): Kazmierski, Wieslaw Mieczyslaw; (Raleigh, NC), Molina, Luis; (Chapel Hill, NC) Correspondence: Stephen B Maebius; Foley And Lardner; 3000 K Street N W Suite 500; Washington; DC; 20007-5109; US Patent Application Number: 20020091113 Date filed: October 5, 2001 Abstract: The use of transition metal complexes in the treatment of septic shock in particular the hypotension associated therewith and pharmaceutical formulations comprising such complexes are disclosed. The use of such transition metal complexes in the treatment of other conditions caused by pathological NO production are also disclosed. Excerpt(s): The present invention relates to the use of transition metal complexes for the treatment of septic shock, and in particular the hypotension associated therewith. Garavilla et al. (Drug. Dev. Res. 25 139-148, (1992)) disclose deferoxamine-manganese complexes which are superoxide dismutase mimics and improve survival following haemorrhagic and endotoxic shock. Sanan et al (Pharmacos 28:103-105, (1985)) disclose the use of desferrioxamine mesylate to increase the survival rate of anaesthetised dogs subjected to haemorrhagic shock U.S. Pat. No. 5,296,466 discloses the use of an iron hemoprotein for the treatment of systemic hypotension or other pathogenic syndromes induced by inappropriate NO production. It has now been found hat transition metal complexes increase the survival rate in mice subjected to endotoxin induced septic shock. The term `transition metal complex` will be understood by one skilled in the art as a transition metal which is linked to one or more chelating agents (ligands). All transition metal complexes other than deferoxamine-manganese, hemin, diethyldithiocaramic acid complexes and iron hemoproteins are included. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Triple drug therapy for the treatment and prevention of acute or chronic pain Inventor(s): Ockert, David M.; (New York, NY) Correspondence: Price Heneveld Cooper Dewitt & Litton; 695 Kenmoor, S.E.; P O Box 2567; Grand Rapids; MI; 49501; US Patent Application Number: 20020058656 Date filed: August 17, 2001 Abstract: A triple drug therapy, pharmaceutical kit, composition, and method of treatment regimen utilized as a combination of effective amounts of an anxiolytic agent, centrally acting alpha antiadrenergic agent, and central nervous system stimulant for the reduction or prevention of dizziness, drowsiness, depression, delirium, lethargy, mania,
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orthostatic hypotension, restlessness, weakness in the extremities, and difficulty in being mobile negative side effects caused by therapeutic agents utilized in the treatment of acute and chronic pain syndromes. Excerpt(s): This application claims priority under 35 U.S.C.sctn.119(e) on U.S. Provisional Application No. 60/233,518, filed Sep. 19, 2000, the entire disclosure of which is incorporated herein by reference. The present invention relates to the treatment and prevention of acute or chronic pain syndromes. Pain sensation is complex and variable. Experiences considered painful by one subject may not be equally painful to another and may vary in the same subject depending on the circumstances presented. In addition, subjective experiences, i.e. "phantom limb pain" make it clear that there is a strong psychological component to pain. Wingard et al., Human Pharmacology: Molecular to Clinical, Mosby-Year Book, Inc., 1991, p. 383. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
USE OF MORPHINE DERIVATIVES AS MEDICAMENTS FOR THE TREATMENT OF NEUROPATHIC PROBLEMS Inventor(s): Buschmann, Helmut; (Aachen, DE), Krueger, Thomas; (Langerwehe-Schlich, DE), Reiss-Mueller, Elke; (Bielefeld, DE), Strassburger, Wolfgang; (Wuerselen, DE), Wnendt, Stephan; (Aachen, DE) Correspondence: Crowell & Moring Llp; Intellectual Property Group; P.O. Box 14300; Washington; DC; 20044-4300; US Patent Application Number: 20020165247 Date filed: February 15, 2002 Abstract: A method for agonizing or antagonizing the ORL1 (opioid receptor-like) receptor of the nociceptin/orphanin FQ ligand ORL1 receptor system using a morphinan compound of the general formula I or derivatives thereof. Also disclosed are methods for treating neuropathic pain and/or anxiolysis and/or depression and/or diuresis and/or urinary incontinence and/or hypotension and or hypertension and/or senile dementia and/or Alzheimer's disease and/or general cognitive dysfunctions and/or tinnitus and/or impaired hearing and/or epilepsy and/or obesity and/or cachexia. Excerpt(s): The present application is a continuation of international patent application no. PCT/EP00/07585, filed Aug. 4, 2000, designating the United States of America, the entire disclosure of which is incorporated herein by reference. Priority is claimed based on Federal Republic of Germany patent application no. 199 39 044.4, filed Aug. 18, 1999. The present invention relates to the use of morphinan derivatives as well as their bases or salts of physiologically compatible acids as regulators for the nociceptin/orphanin FQ ligand ORL1 receptor system and for the production of a medicament. The heptadecapeptide nociceptin/orphanin FQ is an endogenous ligand of the ORL1 (opioid receptor-like) receptor (Meunier et al., Nature 377, 1995, pp. 532-535) that belongs to the family of opioid receptors and can be found in many regions of the brain and spinal cord (Mollereau et al., FEBS Letters, 341, 1994, pp. 33-38, Darland et al., Trends in Neurosciences, 21, 1998, pp. 215-221). The peptide is characterised by a high affinity, with a K.sub.d value of around 56 pM (Ardati et al., Mol. Pharmacol. 51, pp. 816-824), and by a high selectivity for the ORL1 receptor. The ORL1 receptor is homologous to the.mu.,.kappa. and.delta. opioid receptors, and the amino acid sequence of the nociceptin/orphanin FQ peptide has a strong similarity to those of the known opioid
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peptides. The activation of the receptor induced by nociceptin/orphanin FQ leads via the coupling with G.sub.i/o proteins to an inhibition of adenylate cyclase (Meunier et al., Nature 377, 1995, pp. 532-535) Also, at the cellular level there are functional similarities between the.mu.,.kappa. and.delta. opioid receptors and the ORL1 receptor as regards the activation of the potassium channel (Matthes et al., Mo. Pharmacol. 50, 1996, pp. 447-450; Vaughan et al., Br. J. Pharmacol. 117, 1996, pp. 1609-1611) and the inhibition of the L, N and P/Q type calcium channels (Conner et al., Br. J. Pharmacol. 118, 1996, pp. 205-207; Knoflach et al., J. Neuroscience 16, 1996, pp. 6657-6664). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Use of selective antagonists of the alpha1b-adrenergic receptor for improvement of sexual dysfunction Inventor(s): Leonardi, Amedeo; (US), Motta, Gianni; (US), Sironi, Giorgio; (US), Testa, Rodolfo; (US) Correspondence: Darby & Darby P.C.; 805 Third Avenue; New York; NY; 10022; US Patent Application Number: 20020161009 Date filed: August 22, 2001 Abstract: Described is the use in the treatment of either male or female sexual dysfunction of selective antagonists of the.alpha.sub.1B-adrenergic receptor and the pharmaceutical compositions containing them as compounds capable of helping the sexual act avoiding at the same time excessive side effects due to acute hypotension. Excerpt(s): This application claims priority from Italian Patent Application MI 99A 000995 filed May 7,1999 and from U.S. Provisional Application 60/183,257 filed Feb. 17, 2000. The foregoing are incorporated by reference in their entirety. This invention relates to the use in the treatment of human sexual dysfunction of selective antagonists of the.alpha.sub.1b-adrenergic receptor and to pharmaceutical compositions containing them as compounds for assisting the sexual act. Sexual dysfunction is the result of different mechanisms in males and females. In males impotence is defined as the inability to obtain an erection sufficient for intercourse. Erection is achieved as a result of blood inflow into the corpora cavernosa of the penis, which produces engorgement of the corpora cavernosa, and subsequent penile erection. It is estimated that as many as 30 million American men experience some degree of erectile dysfunction, the prevalence of which increases with age (Feldman et al., J. Urol. 151: 5461, 1994). 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 hypotension, 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 “hypotension” (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 hypotension.
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You can also use this procedure to view pending patent applications concerning hypotension. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.
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CHAPTER 6. BOOKS ON HYPOTENSION Overview This chapter provides bibliographic book references relating to hypotension. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on hypotension 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 “hypotension” (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 hypotension: •
Medical Emergencies in the Dental Office. 5th ed Source: St. Louis, MO: Mosby, Inc. 2000. 540 p. Contact: Available from Mosby, Inc. 11830 Westline Industrial Drive, St. Louis, MO 63146. (800) 426-4545. E-mail:
[email protected]. Website: www.mosby.com. PRICE: $52.95 plus shipping and handling. ISBN: 1556644205. Summary: Maintaining a high level of skill in the prevention, recognition, and management of medical emergencies is important in the field of dentistry. This textbook covers the management of medical emergencies in the dental office. Thirty chapters are offered in eight sections: prevention, unconsciousness, respiratory distress, altered consciousness, seizures, drug related emergencies, chest pain, and cardiac arrest. Specific topics include medicolegal considerations, vasodepressor syncope (fainting), postural hypotension (low blood pressure and feeling faint upon getting up from a prone or semi prone position), acute adrenal insufficiency, differential diagnosis, airway
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obstruction, hyperventilation, asthma, heart failure, acute pulmonary edema (fluid in the lungs), diabetes mellitus, thyroid gland dysfunction, cerebrovascular accident (stroke), drug overdose reactions, allergy, angina pectoris, acute myocardial infarction, and cardiac arrest and cardiopulmonary resuscitation. The text concludes with a quick reference section to life threatening situations (offered in algorithm format) and a subject index. Each chapter includes black and white photographs and extensive references. •
Therapy for Diabetes Mellitus and Related Disorders. 3rd ed Source: Alexandria, VA: American Diabetes Association. 1998. 487 p. Contact: Available from American Diabetes Association (ADA). Order Fulfillment Department, P.O. Box 930850, Atlanta, GA 31193-0850. (800) 232-6733. Fax (770) 4429742. Website: www.diabetes.org. PRICE: $39.95 plus shipping and handling. ISBN: 0945448945. Summary: This handbook focuses on the treatment of problems that are of importance in the management of people with diabetes mellitus. The book attempts to help health professionals apply major advances in health care to their patients. Topics include the diagnosis and classification of diabetes mellitus, genetic counseling for type 1 diabetes, gestational diabetes mellitus, the management of pregnant women who have diabetes, antepartum and intrapartum obstetric care, neonatal problems and their management, type 1 diabetes and diabetic ketoacidosis in children, psychosocial adjustment in children who have type 1 diabetes, psychosocial aspects in adults, diabetic ketoacidosis and hyperosmolar hyperglycemic nonketotic syndrome in adults, and lactic acidosis. Other topics include the role of diabetes education in patient management; self monitoring of blood glucose; the rationale for management of hyperglycemia; medical nutrition therapy; pharmacological treatment of obesity; exercise; oral hypoglycemic agents such as sulfonylureas, repaglinide, metformin, alpha glucosidase inhibitors, and thiazolidinediones; insulin treatment; insulin pump therapy; combination therapy for 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.
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 “hypotension” at online booksellers’ Web sites, you may
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discover non-medical books that use the generic term “hypotension” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “hypotension” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •
Clinical hypertension and hypotension; ISBN: 082471279X; http://www.amazon.com/exec/obidos/ASIN/082471279X/icongroupinterna
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New Aspects in Regional Anesthesia 4: Major Conduction Block: Tachyphylaxis, Hypotension, Opiates (Anesthesiology & Intensive Care Medicine, Bd 17) by H.J. Wust (Editor), M. D'Arcy Stanton-Hicks (Editor); ISBN: 038715938X; http://www.amazon.com/exec/obidos/ASIN/038715938X/icongroupinterna
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New Aspects in Regional Anesthesia IV: Major Conduction Block: Tachyphylaxis, Hypotension, and Opiates by H. Wust (Editor), M. D'arcy (Editor); ISBN: 354015938X; http://www.amazon.com/exec/obidos/ASIN/354015938X/icongroupinterna
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Orthostatic Hypotension by Irwin J. Schatz; ISBN: 0803677375; http://www.amazon.com/exec/obidos/ASIN/0803677375/icongroupinterna
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The Official Patient's Sourcebook on Orthostatic Hypotension: A Revised and Updated Directory for the Internet Age by Icon Health Publications; ISBN: 0597830924; http://www.amazon.com/exec/obidos/ASIN/0597830924/icongroupinterna
Chapters on Hypotension In order to find chapters that specifically relate to hypotension, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and hypotension 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 “hypotension” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on hypotension: •
Hypertension Source: in Little, J.W., et al. Dental Management of the Medically Compromised Patient. 5th ed. St. Louis, MO: Mosby, Inc. 1997. p. 176-191. 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 chapter on hypertension (high blood pressure) is from a text that provides the dental practitioner with an up to date reference work describing the dental management of patients with selected medical problems. Hypertension is an abnormal elevation of arterial pressure that, if sustained and untreated, is associated with a significant increase in morbidity and mortality. The dental patient with hypertension poses some significant management considerations. These include identification, monitoring, stress and anxiety reduction, avoidance of drug interactions, awareness and management of drug side effects (such as orthostatis hypotension), and management of drug effects on the oral tissues. The authors discuss
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incidence and etiology of hypertension, pathophysiology and complications, signs and symptoms (clinical presentation and laboratory findings), the medical management of patients with hypertension, and the dental management of this population, including dental treatment planning. 4 figures. 8 tables. 37 references. •
Clinical Disorders of Renal Function in Acute Liver Failure Source: in Arroyo, V., et al, eds. Ascites and Renal Dysfunction in Liver Disease: Pathogenesis, Diagnosis, and Treatment. Malden, MA: Blackwell Science, Inc. 1999. p.6378. Contact: Available from Blackwell Science, Inc. 350 Main Street, Malden, MA 02148. (800) 215-1000 or (781)-388-8250. Fax (781) 388-8270. E-mail:
[email protected]. Website: www.blackwellscience.com. PRICE: $125.00 plus shipping and handling. ISBN: 0632043423. Summary: Acute liver failure (ALF) is a core term that identifies a group of patients developing encephalopathy (abnormal function of the brain tissues) less than 12 weeks after the onset of jaundice, in the absence of underlying liver disease. These patients have important differences in clinical features and prognosis, depending on the etiology (cause), the time from the onset of jaundice to the development of encephalopathy, and the functional hepatic (liver) reserve. The development of renal (kidney) failure in such patients is commonplace. This chapter on clinical disorders of kidney function in ALF is from a textbook on ascites and renal dysfunction in liver disease. The key pathophysiologic features associated with the development of kidney failure are a decrease in kidney blood flow as a consequence of systemic hypotension (low blood pressure), and vasoconstriction within the kidney circulation. The causes of vasoconstriction are multifactorial, including activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system and the development of endotoxemia with production of eicosanoids and free radicals. The chapter concludes with a discussion of renal function as a preoperative risk factor for early posttransplant mortality (death) and a review of treatment strategies for these disorders of kidney function in ALF. 3 figures. 1 table. 81 references.
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Complications of Chronic Dialysis Therapy Source: in Gutch, C.F.; Stoner, M.H.; Corea, A.L. Review of Hemodialysis for Nurses and Dialysis Personnel. 6th ed. St. Louis, MO: Mosby. 1999. p. 192-212. Contact: Available from Harcourt Publishers. Foots Cray High Street, Sidcup, Kent DA14 5HP UK. 02083085700. Fax 02083085702. E-mail:
[email protected]. Website: www.harcourt-international.com. PRICE: $37.95 plus shipping and handling. ISBN: 0815120990. Summary: Chronic dialysis therapy has extended the lives of hundreds of thousands of patients. The treatment, however, can be associated with significant acute and chronic complications. This chapter on the complications of chronic dialysis therapy is from a nursing text that poses questions and then answers those questions with the aim of giving a good understanding of the basic principles, basic diseases, and basic problems in the treatment of kidney patients by dialysis. Many complications in patients with end stage renal disease (ESRD) are part of the uremic syndrome and are unrelated to the dialysis treatment itself. Dialysis related complications include central nervous system (CNS) abnormalities (headache, weakness, fatigue, apathy, nausea), hypotension (low blood pressure), fluid overload (edema), hypertension (high blood pressure), congestive heart failure, arrhythmias, muscle cramping, chills and fever (febrile reactions), allergic
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reactions, and itching (pruritis). The author discusses medical problems associated with ESRD, including anemia and its treatment (often with erythropoietin or transfusions), the complications of blood transfusions, renal osteodystrophy (bone disease related to abnormalities of calcium and phosphorus metabolism), joint disorders (including pseudogout, which is related to elevated uric acid levels), dialysis amyloidosis, carpal tunnel syndrome (CTS), gastrointestinal problems (peptic ulcer disease, constipation, and ascites, or fluid collection in the peritoneal cavity), hepatitis, neuropathy, reproduction problems, and insomnia (inability to sleep). The authors concludes with a discussion of dialysis in the elderly, the role of exercise for dialysis patients, dialysis for people with diabetes mellitus, and the psychological consequences of long term dialysis. •
Complications of Dialysis in Diabetic Patients Source: in Lameire, N. and Mehta, R.L., eds. Complications of Dialysis. New York, NY: Marcel Dekker, Inc. 2000. p. 697-704. Contact: Available from Marcel Dekker, Inc. Cimarron Road, P.O. Box 5005, Monticello, NY 12701. (800) 228-1160 or (845) 796-1919. Fax (845) 796-1772. E-mail:
[email protected]. International E-mail:
[email protected]. Website: www.dekker.com. PRICE: $250.00 plus shipping and handling. ISBN: 0824788710. Summary: Dialysis patients with diabetes mellitus comprise the largest subgroup of patients in end stage renal disease (ESRD) treatment programs in developed countries. This patient population is unfortunately also subject to greater morbidity and mortality when compared to nondiabetic dialysis patients. This chapter on the complications of dialysis in patients with diabetes is from a book that offers a comprehensive, multidisciplinary resource for the nephrologist and caregiver providing dialysis, covering all aspects of dialysis therapies and their complications. The authors of this chapter note that older age at the time of dialysis initiation and the presence of often advanced microvascular and macrovascular disease account for this excess rate of complications and death on dialysis. The management of dialysis patients with diabetes requires an aggressive, preemptive, multidisciplinary, and patient education oriented approach, which must often be led by the nephrologist (kidney specialist) who has the most frequent contact with the patient. Peripheral vascular, cardiovascular, and cerebrovascular disease, retinopathy (eye disease), gastropathy, and dialysis associated complications are the major contributors to co-morbidity in diabetic dialysis patients. Hemodialysis related complications include hypotension (low blood pressure), hypertension (high blood pressure), high interdialytic weight gain, vascular access problems, access thrombosis (clotting), ischemic monomelic neuropathy, and venous hypertension. Other problems discussed include bone disease, diabetic retinopathy, undernutrition, and hyperglycemia (high blood sugar levels). The complications of peritoneal dialysis in patients with diabetes including peritonitis, underdialysis, undernutrition, and hyperglycemia. The authors conclude by noting that the increasing prevalence of type 2 diabetes will require that nephrologists target the problems prevalent in this population in order to reduce morbidity (illness) and mortality (death). 2 tables. 46 references.
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Cardiac Disease in Dialysis Patients Source: in Nissenson, A.R., Fine, R.N., and Gentile, D.E. Clinical Dialysis. 3rd ed. Norwalk, CT: Appleton and Lange. 1995. p. 652-698. Contact: Available from Appleton and Lange. 25 Van Zant Street, East Norwalk, CT 06855. PRICE: $215.00. ISBN: 0838513794.
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Summary: Heart disease is the leading cause of death in the dialysis population, accounting for nearly 40 percent of deaths among these patients. In this chapter, from a medical text on clinical dialysis, the authors examine disorders of the heart that are most prevalent in patients with chronic kidney failure. The authors also put into perspective the factors associated with end-stage renal disease (ESRD) and its treatment that adversely affect myocardial performance. They also discuss methods of evaluating these diseases in the dialysis population, and assess methods that may be useful in the management of heart disease in such individuals. Specific disorders include extracellular fluid and plasma volume overload, anemia, arteriovenous fistulas (for circulatory access), uremic cardiomyopathy, acquired valvular disease, and infective endocarditis. The results of dialysis on cardiac function include acute hemodynamic effects, effects in patients with normal and abnormal left ventricular function, recurrent hypotension, and disturbances of heart rhythm. The chapter concludes with a section discussing uremic pericarditis, a less frequent but more dramatic cardiac complication of uremia. 3 figures. 1 table. 570 references. •
Neuropathy Source: in Devlin, J.T. and Schneider, S.H., eds. Handbook of Exercise in Diabetes. Alexandria, VA: American Diabetes Association. 2002. p.463-496. 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: $69.95 plus shipping and handling. ISBN: 1580400191. Summary: Neuropathy (nerve disease) complicates the management of diabetes. This chapter on diabetic neuropathy (nerve disease associated with diabetes) is from a book that provides a practical, comprehensive guide to diabetes and exercise for health care professionals involved in patient care. Somatic neuropathy (calluses and warm insensate feet) with loss of reflexes or vibration perception increases susceptibility to ulcers, Charcot joint destruction, and limb loss. Autonomic nerve dysfunction impairs the ability to exercise because of decreased systolic and diastolic cardiac function; postural hypotension (low blood pressure) and nocturnal or supine hypertension (high blood pressure); impaired cutaneous (skin) blood flow and sweating; impaired pupillary reaction and night vision; and gastroparesis (reduced gastrointestinal motility) with irregular fuel delivery. Preferred exercise for this population are non weight-bearing. Rates of perceived exertion is a safer guide for exercise intensity than heart rate. The authors provide a paradigm for exercise in patients with cardiovascular autonomic neuropathy. The authors also note that foot care education reduces the risk of ulcers and gangrene by one-third. 3 figures. 2 tables. 105 references.
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Diabetic Peripheral and Autonomic Neuropathy Source: in Sperling, M.A. Type 1 Diabetes: Etiology and Treatment. Totowa, NJ: Humana Press Inc. 2003. p. 437-461. Contact: Available from Humana Press Inc. 999 Riverview Drive, Suite 208, Totowa, NJ 07512. (973) 256-1699. Fax (973) 256-8341. E-mail:
[email protected]. Website: www.humanapress.com. PRICE: $165.00; plus shipping and handling. ISBN: 896039315. Summary: Several distinct syndromes affecting the peripheral nervous system occur in patients with diabetes. This chapter focuses on the two most common neuropathic complications, diabetic polyneuropathy (DPN) and diabetic autonomic neuropathy (DAN), with a short discussion of polyradiculopathy and mononeuropathies. The
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pathogenesis, diagnosis, epidemiology, and treatment of DPN and DAN are addressed, with an emphasis, when possible on patients with type 1 diabetes. This chapter is from a book in which well-recognized physicians and researchers review the latest thinking about the causes of type 1 diabetes and the best approaches to treating both its acute and chronic complications. Topics covered in this chapter include gastrointestinal autonomic neuropathy, genitourinary autonomic neuropathy, abnormal pupillary function, peripheral autonomic denervation, defective glucose counterregulation, cardiovascular autonomic neuropathy, postural hypotension, cardiac denervation syndrome, gustatory sweating, orthostatic hypotension, and cardiorespiratory arrest. 4 tables. 166 references. •
Tamsulosin: Role in the Management of Benign Prostatic Hyperplasia Source: in Narayan, P. Benign Prostatic Hyperplasia. London, England: Churchill Livingstone. 2000. p. 171-180. Contact: Available from Harcourt Publishers. Foots Cray High Street, Sidcup, Kent DA14 5HP UK. 02083085700. Fax 02083085702. E-mail:
[email protected]. Website: www.harcourt-international.com. PRICE: $149.00 plus shipping and handling. ISBN: 0443056374. Summary: Symptomatic benign prostatic hyperplasia (BPH) is a common disease that affects all men with aging. BPH is currently considered a disease that affects the quality of life; therefore, treatments are currently designed to relieve symptoms and reduce side effects. This chapter on the use of the alpha blocker, tamsulosin, in the clinical management of BPH is from a textbook that compiles data and commentary from the world's leading experts in this field. Approximately 80 percent of the patients receiving drug therapy for BPH are prescribed alpha blockers by their primary care physician. The first two selective, long acting alpha 1 receptor antagonists to be approved for treatment of BPH in the United States were terazosin and doxazosin. Tamsulosin hydrochloride (brand name Flomax), a new class of sulfonyl derivative, a uroselective alpha adrenergic blocker, was FDA-approved in 1997. The authors cover the scientific rationale for this drug use, the structure and classification of alpha adrenergic receptors, the clinical pharmacology and pharmacokinetics of tamsulosin, drug interactions, carcinogenesis (development of cancer), adverse reactions to the drug, and clinical studies investigating its use and efficacy. The authors conclude that tamsulosin overall has several advantages over the alpha blockers currently in use. The long action of tamsulosin allows for once a day dosing. Its therapeutic effect, as indicated by improvements in symptoms score, is realized as early as one week after treatment. Additional advantages include the lack of side effects, even in patients at risk of postural hypotension (low blood pressure) such as the elderly and those on multiple cardiac medications, and patients who have comorbid conditions such as diabetes and cardiac disease. Finally, the lower side effect profile of tamsulosin may also allow its use in combination with other relaxants and newer agents in the treatment of lower urinary tract symptoms. 2 tables. 99 references.
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Solving Neuropathy Problems Source: in Touchette, N. Diabetes Problem Solver. Alexandria, VA: American Diabetes Association. 1999. p. 197-216. 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: $19.95 for members; plus shipping and handling. ISBN: 1570400091.
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Summary: This chapter deals with solving neuropathy problems in people who have diabetes. Too much glucose in the blood can, over time, damage the nerves in the body. Although the nerves of the central nervous system are not usually affected by high blood glucose, the nerves of the peripheral nervous system can become damaged over time. Damage may occur to the sensory nerves that send information about how things feel from the skin and from internal organs to the brain or the motor nerves that send information from the brain to the muscles of the body about how to move. Autonomic nerves that control internal organs or autonomic processes may also be damaged. Both small and large nerve fibers may be affected. Neuropathies may also be classified as focal or diffuse. Mononeuropathy, or focal neuropathy, is caused by damage to a single nerve or group of nerves. The chapter explains how to recognize and handle cranial neuropathy; plexopathy; radiculopathy; and entrapment syndromes such as carpal tunnel syndrome, ulnar nerve entrapment, radial nerve entrapment, and peroneal nerve entrapment. Polyneuropathy is the most common type of neuropathy that occurs in people who have diabetes. This type of neuropathy can affect nerves in many parts of the body. The chapter explains how to recognize, handle, treat, and prevent this condition. Autonomic neuropathy can cause problems with bladder functions; result in cardiovascular problems such as orthostatic hypotension, an abnormal heart rate, and a silent heart attack; cause an inability to sweat; and interfere with the warning signs of hypoglycemia and contribute to hypoglycemia unawareness. The chapter explains how to recognize, handle, treat, and prevent these autonomic neuropathies. •
Medical Emergencies Source: in Lockhart, P.B. Oral Medicine and Hospital Practice. Chicago, IL: Special Care Dentistry. 1997. p. 6.3-6.36. Contact: Available from Special Care Dentistry. 211 East Chicago Avenue, Chicago, IL 60611. (312) 440-2660. Fax (312) 440-2824. PRICE: $27.00 (member) or $30.00 (nonmember), plus shipping and handling; institutional prices and bulk orders available. ISBN: 0965719103. Summary: This chapter is from a manual designed to help dental residents, students, and practitioners engaged in the care of patients in the hospital setting. This chapter discusses medical emergencies. Topics include respiratory difficulty due to foreign body or asthma; cardiac and vascular emergencies, including angina pectoris, myocardial infarction, cardiac arrest, pulmonary edema, and cerebral vascular accident (stroke); allergic reactions; hemostasis, including patient evaluation and the treatment of hemorrhage; syncope, including vasovagal syncope, hypoglycemia, drug reactions, and postural hypotension; shock; adrenal cortical insufficiency; convulsive disorders; drug overdose and toxicity, including asymptomatic and symptomatic patients, narcotic overdose, benzodiazepine overdose, sedative or barbiturate overdose, and local anesthetic toxicity; and the diabetic emergencies of hypoglycemia shock and hyperglycemia coma. Most information is presented in outline format, for ease of access. 9 tables.
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Surgery Source: in Daugirdas, J.T. and Ing, T.S., eds. Handbook of Dialysis. 2nd ed. Boston, MA: Little, Brown and Company. 1994. p. 545-552. Contact: Available from Lippincott-Raven Publishers. 12107 Insurance Way, Hagerstown, MD 21740. (800) 777-2295. Fax (301) 824-7390. E-mail:
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[email protected]. Website: http://www.lrpub.com. PRICE: $37.95. ISBN: 0316173835. Summary: This chapter on surgery is from a handbook that outlines all aspects of dialysis therapy, emphasizing the management of dialysis patients. The authors stress that any operation, ranging from creation of a vascular or peritoneal access (the most common procedures) to open heart surgery, can be performed in dialysis patients without a marked increase in the perioperative morbidity or mortality rate. Topics include preoperative preparation, including fluid status, extent of uremia, electrolyte disorders, acid-base status, hematocrit level, and coagulation profile; intraoperative considerations, notably protection of the vascular access, anesthesia, fluid and electrolyte management, and intraoperative hemodialysis or hemofiltration; and postoperative concerns, including hyperkalemia, hypertension, hypotension, fever, the pulmonary system, and nutrition. The authors present information in outline form, for easy reference. 1 table. 15 references. •
Streptococcal Toxic Shock Syndrome Associated With Necrotizing Fasciitis Source: in Coggins, C.H.; Hancock, E.W.; Levitt, L.J., eds. Annual Review of Medicine, Volume 51, 2000. Palo Alto, CA: Annual Reviews, Inc. 2000. p. 271-288. Contact: Available from Annual Reviews. 4139 El Camino Way, P.O. Box 10139, Palo Alto, CA 94303-0139. (650) 493-4400. E-mail:
[email protected]. Website: www.AnnualReviews.org. Summary: This chapter provides health professionals with information on the demographics, symptoms, signs, diagnosis, clinical course, and treatment of streptococcal toxic shock syndrome (strep TSS) with associated necrotizing fasciitis. Strep TSS is the early onset of shock and organ failure associated with any infection caused by Streptococcus pyogenes. It is a rapidly progressive process that kills 30 to 60 percent of patients in 72 to 96 hours. The initial symptoms of strep TSS depend largely on the site of primary infection. Of all patients with strep TSS, 20 percent experience an influenza like syndrome characterized by fever, chills, myalgia, and diarrhea. In patients who develop deep soft tissue infections, such as necrotizing fasciitis or intrauterine infection, severe pain is the most common initial symptom of strep TSS. Violaceous bullae, hypotension, fever, and evidence of organ failure are late clinical manifestations. Diagnosis is not difficult when all the clinical features of strep TSS are manifest; however, the signs and symptoms may be quite subtle early in the course of illness, and laboratory tests may provide valuable clues to the diagnosis. The challenge to clinicians is to make an early diagnosis and to intervene with aggressive fluid replacement, emergent surgical debridement, and general supportive measures. Superantigens such as pyrogenic exotoxin A interact with monocytes and T lymphocytes in unique ways, resulting in T cell proliferation and watershed production of monokines and lymphokines. Penicillin, though efficacious in mild S. pyogenes infection, is less effective in severe infections because of its short postantibiotic effect, inoculum effect, and reduced activity against stationary phase organisms. Emerging treatments for strep TSS include clindamycin and intravenous gamma globulin. 2 tables and 81 references. (AA-M).
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Difficulties With Haemodialysis Source: in Gabriel, R. Patient's Guide to Dialysis and Transplantation. 4th ed. Hingham, MA: Kluwer Academic Publishers. 1990. p. 81-87.
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Contact: Available from Kluwer Academic Publishers. P.O. Box 358, Accord Station. Hingham, MA 02018. (617) 871-6600. PRICE: $24.50. ISBN: 0792389506. Summary: This chapter, from a patient's guide to the treatment of renal failure, discusses potential difficulties with hemodialysis. Problems associated with hemodialysis can be divided into two groups, technical and psychological. The author notes that often these overlap and one can worsen the other. Specific problems covered include vascular access, needling, under-dialysis, hypotension, post-dialysis 'wash-out', infections, realization of restrictions, readjustment to the dialysis routine, sexual problems, and the feeling of confinement often resulting from long-term dialysis. •
Endoscopic Therapy for Severe Gastrointestinal Bleeding Source: in Schrier, R.W., et al., eds. Advances in Internal Medicine. Vol 40. St. Louis, MO: Mosby-Year Book, Inc. 1995. p. 243-271. Contact: Available from Mosby Year-Book, Inc. 11830 Westline Industrial Drive, St. Louis, MO 63146. (800) 426-4545. Fax (800) 535-9935. E-mail:
[email protected]. PRICE: $72.95. ISBN: 0815183135. ISSN: 00652822. Summary: This chapter, from a yearbook of advances in internal medicine, covers endoscopic therapy for severe gastrointestinal (GI) bleeding. This is defined as documented GI bleeding (i.e., hematemesis, melano, hematochezia, or blood in nasogastric lavage), with orthostatic hypotension, a decrease in hematocrit by 6 to 8 percent, or transfusion of 2 or more units of packed red blood cells (RBCs). Acute care for these patients is provided by a team of physicians including gastroenterologists, surgeons, and critical care specialists. Optimal patient outcome depends on successful medical resuscitation, precise diagnosis of the bleeding site, knowledge of the natural history of different bleeding lesions, and appropriate use of therapeutic endoscopy and surgery. The authors of this chapter outline the recent advances in endoscopic hemostasis of severe upper and lower GI bleeding and compare their role with medical, interventional radiologic, and surgical therapy. Causes of GI bleeding discussed include peptic ulcer, variceal bleeding, erosive esophagitis, Mallory-Weiss tears, Dieulafoy's lesion, upper GI angiomas, upper GI malignancy, aortoenteric fistulas, colonic angiomas, colonic diverticular hemorrhage, colonic tumors, colonic ischemia, and inflammatory bowel disease (IBD). 5 figures. 9 tables. 78 references.
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Hemodialysis Source: in Gonick, H.C., ed. Current Nephrology: Volume 17. St. Louis, MO: MosbyYear Book, Inc. 1994. p. 347-383. Contact: Available from Mosby-Year Book, Inc. 11830 Westline Industrial Drive, St. Louis, MO 63146. (800) 426-4545. PRICE: $82.95. ISBN: 0815137435. ISSN: 01485265. Summary: This chapter, from a yearbook of nephrology, reviews advances in hemodialysis. Topics include statistics from the U.S. Renal Data System, statistics from the European Dialysis and Transplant Registry, vascular access, anticoagulation, water treatment, endotoxins and chloramines, ethylene oxide (ETO), interleukins, protein catabolism, adequacy of dialysis, dialyzer reuse, hypotension during and after hemodialysis, vasoactive peptides, cramps, cardiac arrhythmias, erythropoietin, atherosclerosis and lipids, endothelin, carnitine and lipids, hepatitis C, HIV, peripheral neuropathy, the brain, sleep disorders, pruritus, thyroid function, growth hormone and pituitary function, trace elements, zinc, beta 2-microglobulin, acquired cystic disease, quality of life, and patient survival. 9 figures. 137 references.
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Causes and Treatment of Priapism Source: in Rous, S.E., ed. 1997 Urology Annual: Volume 11. Oxford, England: Blackwell Science Ltd. 1997. 321 p. Contact: Available from Blackwell Science, Inc. 238 Main Street, Cambridge, MA 02142. (800) 215-1000 or (617) 876-7000. Fax (617) 492-5263. PRICE: $125.00. ISBN: 0865425671. Summary: This entry from the Urology Annual outlines the causes and treatments of priapism. Priapism is broadly defined as the state of persistent erection for more than 4 to 6 hours and unassociated with sexual gratification. Pain may or may not be present, depending on the etiology. Topics include the pathophysiology of the normal process of erection and detumescence, neuroanatomy and neurophysiology, primary and secondary causes of priapism, evaluation and management issues, and priapism in childhood. Primary priapism may be subdivided into idiopathic and psychic categories. Idiopathic refers to cases without psychic or physical activity with no identifiable secondary factors contributing to its occurrence. Psychic priapism may be caused by prolonged or deviant sexual behavior, resulting in genital overactivity. Secondary priapism may be related to a number of etiologic factors including neurogenic causes, infectious processes, toxins, local stimuli, inflammatory diseases, trauma, malignancy, hematologic abnormalities, and drug related or other miscellaneous causes. The goal of treatment of priapism is detumescence (resolution of erection), relief of pain, and preservation of erectile function. Medical management options include hydration, oxygenation, radiation therapy, ice packs, sedation, compression (pneumatic cuff around the penis), physostigmine, steroids, prostatic massage, rectal lavage, anticoagulation, female hormones, controlled hypotension, spinal and local anesthesia, ketamine, terbutaline, enzymatic lysis of the thrombus in the corpora, intracavernous injection of sympathomimetic agents, and percutaneous embolization of the affected vessel. Surgical strategies are also available. 1 figure. 1 table. 200 references.
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Pediatric Hemodialysis Source: in Gutch, C.F.; Stoner, M.H.; Corea, A.L. Review of Hemodialysis for Nurses and Dialysis Personnel. 6th ed. St. Louis, MO: Mosby. 1999. p. 288-299. Contact: Available from Harcourt Publishers. Foots Cray High Street, Sidcup, Kent DA14 5HP UK. 02083085700. Fax 02083085702. E-mail:
[email protected]. Website: www.harcourt-international.com. PRICE: $37.95 plus shipping and handling. ISBN: 0815120990. Summary: Treating children who need hemodialysis is complicated by the fact that they are still growing and developing, and chronic renal insufficiency and end stage renal disease (ESRD) interfere with this normal growth and development. Thus, pediatric nephrology nurses must have a comprehensive knowledge of pediatric nursing and childhood growth and development. This chapter on pediatric hemodialysis is from a nursing text that poses questions and then answers those questions with the aim of giving a good understanding of the basic principles, basic diseases, and basic problems in the treatment of kidney patients by dialysis. The authors of the chapter emphasize that the hybrid of services that a pediatric dialysis facility provides necessitates a good method of matching resources to patient workload activity. Acute renal failure in children usually results from hypoperfusion of the kidneys due to septic shock, hypotension, severe dehydration from gastroenteritis, or from acute blood loss from surgery or an accident. The pathology is that of acute tubular necrosis (ATN). The causes of end stage renal disease (ESRD) are different for children than for adults. About two thirds of the cases in children are caused by congenital urinary tract anomalies, or
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hereditary diseases; the other third are caused by acquired kinds of glomerulonephropathy. Unlike ESRD in adults, diabetic nephropathy, chronic hypertension, autosomal dominant polycystic kidney disease, and membranous glomerulonephritis are rarely causes of ESRD in childhood and adolescence. The preferred modality of treatment for ESRD for most pediatric patients is renal transplantation. If a pediatric patient needs chronic dialysis, home peritoneal dialysis is the usual choice, but may not always be possible. The authors review the details of incenter hemodialysis, including preferred measures of weight, isolation, limits for extracorporeal volume, vascular access considerations, special dialyzers, equipment and supplies, pain with hemodialysis, ultrafiltration, determining blood flow rate, intradialytic monitoring, high blood pressure in children, anemia management, growth and development concerns, toileting concerns, school scheduling, and emergency preparedness. •
Complications During Hemodialysis Source: in Nissenson, A.R.; Fine, R.N. Dialysis Therapy. Philadelphia, PA: Hanley and Belfus, Inc. 2002. p. 171-179. Contact: Available from Hanley and Belfus, Inc. Medical Publishers, 210 South 13th Street, Philadelphia, PA 19107. (215) 546-7293 or (215) 546-4995. (800) 962-1892. Fax: (215) 790-9330. Website: www.hanleyandbelfus.com. PRICE: $59.95; plus shipping and handling. ISBN: 1560534265. Summary: With improving outcomes, replacement of renal (kidney) function by hemodialysis (HD) is a well established therapy, but it is not free of complications. This chapter is one part of a section on complications during hemodialysis, from a textbook on dialysis therapy. The chapter covers hypotension (low blood pressure), muscle cramps, dialyzer reactions, hypoxemia (low levels of oxygen in the blood), febrile (fever) reactions, dialysis disequilibrium syndrome (DDS, a neurologic disorder characterized by headaches and nausea in the mild form and confusion, blurred vision, seizures and even coma in the more severe forms), bleeding, pruritis (itching), heart rate disturbances, cardiopulmonary arrest (heart stopping) during dialysis, air embolism (a rare complication), hemolysis (the breakdown of red blood cells), and electrolyte disturbances. The author concludes that the incidence of clinical problems during HD has been greatly reduced, thanks to technological advances and to higher standards in the routine delivery of therapy. Despite these advances, clinical problems may still occur, especially in elderly or unstable patients, or in individuals with underlying comorbid (other illness present at the same time) conditions. Accurate supervision and physical examination of the patient may prevent several of these problems. Hemodialysis can be better tolerated and done more smoothly when potential clinical problems are anticipated and appropriate countermeasures are instituted in a timely fashion. 3 figures.
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Diabetes and Hypertension Source: in Johnstone, M.T. and Veves, A. Diabetes and Cardiovascular Disease. Totowa, NJ: The Humana Press, Inc. 2001. p. 123-129. 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
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that will assume epidemic proportions as the population grows older. This chapter on diabetes and hypertension is from a textbook that offers physicians practical knowledge about cardiovascular disease and diabetes. This chapter is in Part I, which focuses on pathophysiology, including the mechanisms and risk factors for diabetic cardiovascular disease. The author notes that many factors contribute to increased cardiovascular disease (CVD) in persons with diabetes. These factors include hypertension (high blood pressure), dyslipidemia (disordered levels of fats in the blood), platelet hyperactivity, endothelial (the cells lining the body cavity and cardiovascular system) abnormalities, as well as hyperglycemia (high blood glucose), microalbuminuria (protein in the urine), and hyperinsulinemia (high levels of insulin in the blood). The author discusses characteristics of hypertension in people with diabetes and then focuses on treatment goals in this population. The goal of hypertension treatment in persons with diabetes is to prevent hypertension-associated death and disability. The level of blood pressure and the diagnosis of hypertension should be based on multiple blood pressure measurements obtained in a standardized fashion on at least three occasions. Because of the tendency to orthostatic hypotension (abnormally low blood pressure upon standing), standing blood pressures should be measured at each office visit. Pharmacologic (drug) therapy should be initiated when lifestyle modifications do not lower blood pressure to less than 130 over 85 mmHg in people with diabetes. Combination therapy is usually necessary for adequate blood pressure control; therapy should include an ACE inhibitor for maximal benefits in protecting against cardiovascular disease as well as renal (kidney) disease. 1 figure. 1 table. 30 references.
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CHAPTER 7. MULTIMEDIA ON HYPOTENSION Overview In this chapter, we show you how to keep current on multimedia sources of information on hypotension. 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 hypotension is the Combined Health Information Database. You will need to limit your search to “Videorecording” and “hypotension” 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 “hypotension” (or synonyms) into the “For these words:” box. The following is a typical result when searching for video recordings on hypotension: •
Nephrology Update Source: Cleveland, OH: Cleveland Clinic Foundation. 1992. (videocassettes, proceedings/minutes). Contact: Available from CME Video. 2000 Crawford Place, Suite 100, Mount Laurel, NJ 08054. (800) 284-8433. PRICE: $495; plus $18.25 shipping and handling; Group Practice Package $150 plus $5.25 shipping and handling. Program Number 076. Summary: This Video Education Program presents 23 hours of presentations and problem-solving workshops. Topics include the clinical applications of basic renal physiology; the biology of mesangial cell structure and function; the diagnosis and management of hypercalcemia; mechanisms of dialysis-induced hypotension; HIV nephropathy; renal artery stenosis; the pathogenesis of renal stones; glomerulonephritis; dietary treatment in chronic renal disease; drug-induced acute and chronic interstitial nephritis; issues in metabolic acidosis; prostatic disease; hypertension; systemic lupus erythematosus nephritis; and the thrombotic angiopathies. Workshops cover topics
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including: management issues in dialysis patients, access, adequacy and nutrition; complex acid-base disorders; and intensive care unit (ICU) nephrology. All tapes are indexed with Quik-Scan for fast reference to presentations of special interest to the viewer. The program is accompanied by the original course syllabus, including supplemental reference information.
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CHAPTER 8. PERIODICALS AND NEWS ON HYPOTENSION Overview In this chapter, we suggest a number of news sources and present various periodicals that cover hypotension.
News Services and Press Releases One of the simplest ways of tracking press releases on hypotension 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 “hypotension” (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 hypotension. 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 “hypotension” (or synonyms). The following was recently listed in this archive for hypotension: •
Hypotension common after treatment of carotid artery stenosis Source: Reuters Medical News Date: November 18, 2003
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Protamine-associated hypotension associated with post-CABG mortality Source: Reuters Industry Breifing Date: March 26, 2003
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Sicor gains FDA OK for generic hypotension drug Source: Reuters Industry Breifing Date: March 04, 2003
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Systemic hypotension strongest predictor of death after severe blunt head injury Source: Reuters Medical News Date: April 08, 2002
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Hypotension tied to cognitive impairment in elderly heart failure patients Source: Reuters Medical News Date: December 10, 2001
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Sildenafil effective in patients with parkinsonism, but hypotension may occur Source: Reuters Industry Breifing Date: September 18, 2001
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Midodrine use safe and effective for hypotension during dialysis Source: Reuters Industry Breifing Date: April 23, 2001
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MetaPhore Pharmaceutical's new enzyme eliminates IL-2 hypotension in mice Source: Reuters Industry Breifing Date: March 27, 2001
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Dopamine agonist therapy for Parkinson's often causes orthostatic hypotension Source: Reuters Industry Breifing Date: October 20, 2000
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Hypotension in elderly a marker for depression Source: Reuters Medical News Date: March 08, 2000 The NIH
Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine. Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name. Market Wire Market Wire is more focused on technology than the other wires. To browse the latest press releases by topic, such as alternative medicine, biotechnology, fitness, healthcare, legal, nutrition, and pharmaceuticals, access Market Wire’s Medical/Health channel at http://www.marketwire.com/mw/release_index?channel=MedicalHealth. Or simply go to
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Market Wire’s home page at http://www.marketwire.com/mw/home, type “hypotension” (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 “hypotension” (or synonyms). If you know the name of a company that is relevant to hypotension, you can go to any stock trading Web site (such as http://www.etrade.com/) and search for the company name there. News items across various news sources are reported on indicated hyperlinks. Google offers a similar service at http://news.google.com/. BBC Covering news from a more European perspective, the British Broadcasting Corporation (BBC) allows the public free access to their news archive located at http://www.bbc.co.uk/. Search by “hypotension” (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 “hypotension” (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 hypotension: •
Role of Nitric Oxide in Hirschsprung's Disease Source: Messenger. 8(2): 10. 1996. Contact: Available from American Pseudo-obstruction and Hirschsprung's Disease Society (APHS). 158 Pleasant Street, North Andover, MA 01845. (978) 685-4477. Fax (978) 685-4488. E-mail:
[email protected]. Summary: During the past decade, the understanding of gastrointestinal motility has been changed tremendously by the discovery of a neurotransmitter, nitric oxide (NO). This brief article explores the role of nitric oxide in Hirschsprung's disease. The authors first review the diverse roles that NO plays in human physiology; it relaxes vessels, promotes fatal hypotension in septic shock, protects against stomach ulcers (by keeping the gastric mucosal blood flow intact), and prevents atherosclerosis. Hirschsprung's disease is characterized by the lack of ganglion cells and impaired relaxation of the colon (less frequently in other parts of the gut). Researchers have investigated the effect of NO in Hirschsprung's disease. Some of the data support the idea that Hirschsprung's disease is characterized by a deficiency of NO producing nerves in the gut. The study
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confirms NO dependent relaxation in the human colon, so the absence of NO in the gastrointestinal smooth muscle may be responsible for the spasticity of the aganglionic segment in Hirschsprung's disease. •
Cautions in the Use of Oral Agents for the Management of Erectile Dysfunction Source: AUA News. 3(4): 20. July-August 1998. Contact: Available from AUA News. Williams and Wilkins, 351 West Camden Street, Baltimore, MD 21201-2436. Summary: Few if any pharmaceutical agents have experienced more heralded releases or had more public media coverage than Viagra (sildenafil citrate), a new oral therapy for erectile dysfunction. This selective inhibitor of cyclic guanosine monophosphate specific phosphodiesterase type 5 acts on corpus cavernosal smooth muscle (in the penis) and has been extensively evaluated in studies of men with erectile dysfunction (ED) of organic, psychogenic, and mixed etiologies. This brief article reviews the cautions in the use of this drug for the management of ED. In clinical trials, adverse events were reported as mild, including headache, flushing, and dyspepsia occurring in 6 to 18 percent of men. Mild and transient visual effects have also been reported (approximately 3 percent of men). The author reports that as of June 8, 1998, the Food and Drug Administration had received 16 unduplicated reports of deaths of men taking Viagra. At least 3 of the 16 reported deaths occurred in men who were treated with nitroglycerin. The package insert for Viagra clearly states that an absolute contraindication for this drug is the concomitant use of organic nitrates. Because of sildenafil's vasodilatory effects, it acts synergistically with nitrates. During nitrate therapy, high levels of nitric oxide (NO) are present in the circulation. Sildenafil increases the vasodilatory effect of circulating NO, causing precipitous and potentially serious hypotension (low blood pressure). Although most if not all urologists are aware of the contraindication of combining sildenafil and nitrates, this may not be well known to emergency room physicians or technicians. 1 table. 1 reference.
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Diabetic Cardiovascular Autonomic Neuropathy Source: Diabetes News. 17(2): 1-5. 1996. Contact: Available from Excerpta Medica. P.O. Box 1126, 1000 BC Amsterdam, The Netherlands. Summary: This article reviews cardiovascular autonomic neuropathy (CAN), a serious complication of diabetes. CAN is associated with a poor prognosis and may result in severe postural hypotension, exercise intolerance, enhanced intraoperative instability, and possibly an increased incidence of silent myocardial infarction and ischemia. The author discusses the classification of CAN and its prognosis, clinical features, diagnostic assessment, epidemiology, and treatment. The author stresses that the most important therapeutic measure is achievement of the best possible glycemic control. The success of any treatment depends on the severity of CAN, and the best preventive results can be expected when measures are instituted during the early asymptomatic stages of the complication. References are available by request. 1 figure. 1 table. (AA-M).
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Understanding Headaches Source: Fibromyalgia Frontiers. 7(5): 5-7. September-October 1999.
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Contact: Available from National Fibromyalgia Partnership. 140 Zinn Way, Linden, VA 22642-5609. Toll-free phone (866) 725-4404. Fax (540) 622-2998. E-mail:
[email protected]. Website: www.fmpartnership.org. Summary: This newsletter article provides people who have fibromyalgia (FM) with information on the treatment of primary headache disorders. These uncomfortable disorders are usually benign. Although each headache syndrome has its own distinctive pain patterns, vascular headaches and tension headaches have overlaps in treatment. The mainstays of preventive medication in the treatment of vascular headaches and tension headaches are the tricyclics and beta blockers. Selective serotonin uptake inhibitors, which are sometimes helpful in FM, probably help tension headaches more than vascular headaches. The physical approach to the management of vascular headaches is also helpful in treating the patient with FM. Although tension like headaches are believed to be caused by muscle contraction, in patients with FM they may also be related to neurally mediated hypotension. Temporomandibular joint dysfunction (TMD) is very common in these patients, and treatment is similar to that given to others who have TMD. Atypical facial pain syndromes may be more common in patients with FM than in the general population. Other head pain syndromes such as cluster headache and trigeminal neuralgia are no more common in patients with FM than in the general population, so treatments are specific to the particular disorder. People who experience headaches, particularly those who have FM, need to avoid narcotics and other drugs that can cause rebound headaches.
Academic Periodicals covering Hypotension Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to hypotension. In addition to these sources, you can search for articles covering hypotension that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”
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CHAPTER 9. RESEARCHING MEDICATIONS Overview While a number of hard copy or CD-ROM resources are available for researching medications, a more flexible method is to use Internet-based databases. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.
U.S. Pharmacopeia Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications recommended for hypotension. One such source is the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the U.S. Pharmacopeia (USP). Today, the USP is a nonprofit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at http://www.usp.org/. The USP currently provides standards for over 3,700 medications. The resulting USP DI® Advice for the Patient® can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database, located at http://www.fda.gov/cder/da/da.htm. While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopeia (USP). Below, we have compiled a list of medications associated with hypotension. If you would like more information on a particular medication, the provided hyperlinks will direct you to ample documentation (e.g. typical dosage, side effects, drug-interaction risks, etc.). The
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following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to hypotension: Fludrocortisone •
Systemic - U.S. Brands: Florinef http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202244.html
Midodrine •
Systemic - U.S. Brands: ProAmatine http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203640.html
Commercial Databases In addition to the medications listed in the USP above, a number of commercial sites are available by subscription to physicians and their institutions. Or, you may be able to access these sources from your local medical library.
Mosby’s Drug Consult™ Mosby’s Drug Consult™ database (also available on CD-ROM and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Subscription information is available at the following hyperlink: http://www.mosbysdrugconsult.com/. PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html. Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee.
Researching Orphan Drugs Although the list of orphan drugs is revised on a daily basis, you can quickly research orphan drugs that might be applicable to hypotension by using the database managed by the National Organization for Rare Disorders, Inc. (NORD), at http://www.rarediseases.org/. Scroll down the page, and on the left toolbar, click on
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“Orphan Drug Designation Database.” On this page (http://www.rarediseases.org/search/noddsearch.html), type “hypotension” (or synonyms) into the search box, and click “Submit Query.” When you receive your results, note that not all of the drugs may be relevant, as some may have been withdrawn from orphan status. Write down or print out the name of each drug and the relevant contact information. From there, visit the Pharmacopeia Web site and type the name of each orphan drug into the search box at http://www.nlm.nih.gov/medlineplus/druginformation.html. You may need to contact the sponsor or NORD for further information. NORD conducts “early access programs for investigational new drugs (IND) under the Food and Drug Administration’s (FDA’s) approval ‘Treatment INDs’ programs which allow for a limited number of individuals to receive investigational drugs before FDA marketing approval.” If the orphan product about which you are seeking information is approved for marketing, information on side effects can be found on the product’s label. If the product is not approved, you may need to contact the sponsor. The following is a list of orphan drugs currently listed in the NORD Orphan Drug Designation Database for hypotension: •
Midodrine HC1 (trade name: Amatine) http://www.rarediseases.org/nord/search/nodd_full?code=74
•
Midodrine HCI (trade name: Amatine) http://www.rarediseases.org/nord/search/nodd_full?code=810
If you have any questions about a medical treatment, the FDA may have an office near you. Look for their number in the blue pages of the phone book. You can also contact the FDA through its toll-free number, 1-888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.
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APPENDICES
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APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.
NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute11: •
Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm
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National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/
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National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html
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National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25
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National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm
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National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm
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National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375
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National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/
11
These publications are typically written by one or more of the various NIH Institutes.
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National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm
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National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/
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National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm
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National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm
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National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/
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National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/
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National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm
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National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html
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National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm
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National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm
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National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm
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National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html
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National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm
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Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp
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National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/
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National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp
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Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html
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Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm
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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.12 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:13 •
Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html
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HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html
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NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html
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Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/
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Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html
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Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html
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Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/
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Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html
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Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html
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Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html
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MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html
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Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 13 See http://www.nlm.nih.gov/databases/databases.html.
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Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html
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Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html
The NLM Gateway14 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.15 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “hypotension” (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 37379 311 986 67 2700 41443
HSTAT16 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.17 These documents include clinical practice guidelines, quickreference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.18 Simply search by “hypotension” (or synonyms) at the following Web site: http://text.nlm.nih.gov.
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Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.
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The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH). 16 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 17 18
The HSTAT URL is http://hstat.nlm.nih.gov/.
Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations.
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Coffee Break: Tutorials for Biologists19 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.20 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.21 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.
Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are some examples that may interest you: •
CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.
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Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.
The Genome Project and Hypotension In the following section, we will discuss databases and references which relate to the Genome Project and hypotension. Online Mendelian Inheritance in Man (OMIM) The Online Mendelian Inheritance in Man (OMIM) database is a catalog of human genes and genetic disorders authored and edited by Dr. Victor A. McKusick and his colleagues at Johns Hopkins and elsewhere. OMIM was developed for the World Wide Web by the National Center for Biotechnology Information (NCBI).22 The database contains textual information, pictures, and reference information. It also contains copious links to NCBI’s Entrez database of MEDLINE articles and sequence information. 19 Adapted 20
from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html.
The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 21 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process. 22 Adapted from http://www.ncbi.nlm.nih.gov/. Established in 1988 as a national resource for molecular biology information, NCBI creates public databases, conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information--all for the better understanding of molecular processes affecting human health and disease.
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To search the database, go to http://www.ncbi.nlm.nih.gov/Omim/searchomim.html. Type “hypotension” (or synonyms) into the search box, and click “Submit Search.” If too many results appear, you can narrow the search by adding the word “clinical.” Each report will have additional links to related research and databases. In particular, the option “Database Links” will search across technical databases that offer an abundance of information. The following is an example of the results you can obtain from the OMIM for hypotension: •
Hypotension, Orthostatic Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=146500 Genes and Disease (NCBI - Map)
The Genes and Disease database is produced by the National Center for Biotechnology Information of the National Library of Medicine at the National Institutes of Health. This Web site categorizes each disorder by system of the body. Go to http://www.ncbi.nlm.nih.gov/disease/, and browse the system pages to have a full view of important conditions linked to human genes. Since this site is regularly updated, you may wish to revisit it from time to time. The following systems and associated disorders are addressed: •
Cancer: Uncontrolled cell division. Examples: Breast and ovarian cancer, Burkitt lymphoma, chronic myeloid leukemia, colon cancer, lung cancer, malignant melanoma, multiple endocrine neoplasia, neurofibromatosis, p53 tumor suppressor, pancreatic cancer, prostate cancer, Ras oncogene, RB: retinoblastoma, von Hippel-Lindau syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Cancer.html
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Immune System: Fights invaders. Examples: Asthma, autoimmune polyglandular syndrome, Crohn’s disease, DiGeorge syndrome, familial Mediterranean fever, immunodeficiency with Hyper-IgM, severe combined immunodeficiency. Web site: http://www.ncbi.nlm.nih.gov/disease/Immune.html
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Metabolism: Food and energy. Examples: Adreno-leukodystrophy, atherosclerosis, Best disease, Gaucher disease, glucose galactose malabsorption, gyrate atrophy, juvenile-onset diabetes, obesity, paroxysmal nocturnal hemoglobinuria, phenylketonuria, Refsum disease, Tangier disease, Tay-Sachs disease. Web site: http://www.ncbi.nlm.nih.gov/disease/Metabolism.html
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Muscle and Bone: Movement and growth. Examples: Duchenne muscular dystrophy, Ellis-van Creveld syndrome, Marfan syndrome, myotonic dystrophy, spinal muscular atrophy. Web site: http://www.ncbi.nlm.nih.gov/disease/Muscle.html
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Nervous System: Mind and body. Examples: Alzheimer disease, amyotrophic lateral sclerosis, Angelman syndrome, Charcot-Marie-Tooth disease, epilepsy, essential tremor, fragile X syndrome, Friedreich’s ataxia, Huntington disease, Niemann-Pick disease, Parkinson disease, Prader-Willi syndrome, Rett syndrome, spinocerebellar atrophy, Williams syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Brain.html
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Signals: Cellular messages. Examples: Ataxia telangiectasia, Cockayne syndrome, glaucoma, male-patterned baldness, SRY: sex determination, tuberous sclerosis, Waardenburg syndrome, Werner syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Signals.html
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Transporters: Pumps and channels. Examples: Cystic fibrosis, deafness, diastrophic dysplasia, Hemophilia A, long-QT syndrome, Menkes syndrome, Pendred syndrome, polycystic kidney disease, sickle cell anemia, Wilson’s disease, Zellweger syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Transporters.html Entrez
Entrez is a search and retrieval system that integrates several linked databases at the National Center for Biotechnology Information (NCBI). These databases include nucleotide sequences, protein sequences, macromolecular structures, whole genomes, and MEDLINE through PubMed. Entrez provides access to the following databases: •
3D Domains: Domains from Entrez Structure, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo
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Books: Online books, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=books
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Genome: Complete genome assemblies, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Genome
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NCBI’s Protein Sequence Information Survey Results: Web site: http://www.ncbi.nlm.nih.gov/About/proteinsurvey/
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Nucleotide Sequence Database (Genbank): Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Nucleotide
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OMIM: Online Mendelian Inheritance in Man, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM
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PopSet: Population study data sets, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Popset
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ProbeSet: Gene Expression Omnibus (GEO), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo
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Protein Sequence Database: Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Protein
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PubMed: Biomedical literature (PubMed), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed
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Structure: Three-dimensional macromolecular structures, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Structure
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Taxonomy: Organisms in GenBank, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Taxonomy
To access the Entrez system at the National Center for Biotechnology Information, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=genome, and then
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select the database that you would like to search. The databases available are listed in the drop box next to “Search.” Enter “hypotension” (or synonyms) into the search box and click “Go.” Jablonski’s Multiple Congenital Anomaly/Mental Retardation (MCA/MR) Syndromes Database23 This online resource has been developed to facilitate the identification and differentiation of syndromic entities. Special attention is given to the type of information that is usually limited or completely omitted in existing reference sources due to space limitations of the printed form. At http://www.nlm.nih.gov/mesh/jablonski/syndrome_toc/toc_a.html, you can search across syndromes using an alphabetical index. Search by keywords at http://www.nlm.nih.gov/mesh/jablonski/syndrome_db.html. The Genome Database24 Established at Johns Hopkins University in Baltimore, Maryland in 1990, the Genome Database (GDB) is the official central repository for genomic mapping data resulting from the Human Genome Initiative. In the spring of 1999, the Bioinformatics Supercomputing Centre (BiSC) at the Hospital for Sick Children in Toronto, Ontario assumed the management of GDB. The Human Genome Initiative is a worldwide research effort focusing on structural analysis of human DNA to determine the location and sequence of the estimated 100,000 human genes. In support of this project, GDB stores and curates data generated by researchers worldwide who are engaged in the mapping effort of the Human Genome Project (HGP). GDB’s mission is to provide scientists with an encyclopedia of the human genome which is continually revised and updated to reflect the current state of scientific knowledge. Although GDB has historically focused on gene mapping, its focus will broaden as the Genome Project moves from mapping to sequence, and finally, to functional analysis. To access the GDB, simply go to the following hyperlink: http://www.gdb.org/. Search “All Biological Data” by “Keyword.” Type “hypotension” (or synonyms) into the search box, and review the results. If more than one word is used in the search box, then separate each one with the word “and” or “or” (using “or” might be useful when using synonyms).
23
Adapted from the National Library of Medicine: http://www.nlm.nih.gov/mesh/jablonski/about_syndrome.html. 24 Adapted from the Genome Database: http://gdbwww.gdb.org/gdb/aboutGDB.html - mission.
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APPENDIX B. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. Since new guidelines on hypotension 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 hypotension. 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 hypotension. 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 “hypotension”:
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Other guides Degenerative Nerve Diseases http://www.nlm.nih.gov/medlineplus/degenerativenervediseases.html Dietary Sodium http://www.nlm.nih.gov/medlineplus/dietarysodium.html
Within the health topic page dedicated to hypotension, the following was listed: •
General/Overviews Blood Pressure Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=4473 Low Blood Pressure Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=4643
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Diagnosis/Symptoms Blood Pressure Testing and Measurement Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=4470 Tilt-Table Test Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=AN00268
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Specific Conditions/Aspects Autonomic Nervous System Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=4463 Blood Pressure Drops When You Stand Up Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=HQ01027 Multiple System Atrophy with Orthostatic Hypotension Source: National Institute of Neurological Disorders and Stroke http://www.ninds.nih.gov/health_and_medical/disorders/mult_sys_atrophy_doc .htm Orthostatic Hypotension Source: National Institute of Neurological Disorders and Stroke http://www.ninds.nih.gov/health_and_medical/disorders/orthosta_doc.htm
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Organizations American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=1200000 National Heart, Lung, and Blood Institute http://www.nhlbi.nih.gov/
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National Institute of Neurological Disorders and Stroke http://www.ninds.nih.gov/ •
Research Effects of Blood Pressure Measurements on Mortality Source: American College of Physicians http://www.annals.org/cgi/content/full/139/9/I-46
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 hypotension. 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: •
Balance Disorders: Evaluation and Treatment Source: Chatham, IL: Micromedical Technologies, Inc. 1998. 27 p. Contact: Available from Micromedical Technologies. 110 West Walnut Street, Chatham, IL 62629. (800) 334-4154 or (217) 483-2122. Fax (217) 483-4533. E-mail:
[email protected]. Website: www.micromedical.com. PRICE: $6.00. Summary: This booklet offers physicians a short course in the evaluation and treatment of balance disorders. The authors emphasize that the key to successful treatment is a specific and accurate diagnosis. The booklet begins with a section describing the structure and function of the vestibular system, then considers issues of screening patients for referral, including the temporal course, precipitating factors, associated symptoms, general health status, static and dynamic evaluations, eye movement tests, positioning, Rhomberg testing, and the impact of medications on the vestibular system. The next section discusses evaluation techniques, including audiometric evaluation, electronystagmography, rotational tests, posturographic studies, auditory evoked potentials, otoacoustic emissions, and lifestyle considerations. Vestibular pathologies reviewed include labyrinthitis and vestibular neuritis, Meniere's disease, perilymph fistula, benign paroxysmal positional vertigo (BPPV), central dizziness, ototoxicity, acoustic neuroma, vestibular migraines, vascular disorders, hyperventilation, and postural hypotension. The booklet concludes with a discussion of treatment techniques and fall prevention strategies. The booklet also includes a set of statistics about balance disorders, a glossary of terms, and a reference list. 57 references.
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What is Neuropathy? Source: Hollywood, FL: Diabetes Research Institute. 1992. 4 p. Contact: Available from Diabetes Research Institute. 3440 Hollywood Boulevard, Suite 100, Hollywood, FL 33021. (305) 964-4040 or (800) 321-3437. PRICE: Single copy free (donations accepted). Summary: This brochure describes neuropathy associated with diabetes mellitus. Written in a question-and-answer format, the brochure discusses how neuropathy affects the nerves; who gets neuropathy; how a health care provider diagnoses neuropathy; how poor diabetes control impacts neuropathy; peripheral neuropathy and its complications; managing neuropathy-associated pain; foot ulcers and how they occur; amputation and its prevention; preventing foot ulcers; autonomic neuropathy and its complications, including severe insulin reactions and postural hypotension; how autonomic neuropathy affects sexual function; gastroparesis; and other problems associated with autonomic neuropathy.
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Mastocytosis Source: Kirksville, MO: American Osteopathic College of Dermatology (AOCD). 2001. 2 p. Contact: Available online from American Osteopathic College of Dermatology. 1501 East Illinois Street, P.O. Box 7525, Kirksville, MO 63501. (800) 449-2623 or (660) 665-2184. Fax (660) 627-2623. E-mail:
[email protected]. Website: www.aocd.org/skin/dermatologic_diseases/ index.html. Summary: This fact sheet provides the parents of children who have mastocytosis or adults who have mastocytosis with information on the symptoms, diagnosis, and treatment of this group of disorders caused by the presence of too many mast cells. These cells release chemicals that attract white blood cells to areas of the body where they are needed. Mastocytosis can occur in cutaneous and systemic forms. The cutaneous form, which is the most common and is known as urticaria pigmentosa, occurs when mast cells infiltrate the skin. Systemic mastocytosis is caused by the accumulation of mast cells in the tissues. Symptoms of mastocytosis include bone pain, abdominal discomfort, nausea and vomiting, ulcers, diarrhea, skin lesions, hypotension, and shock. Diagnosis of urticaria pigmentosa is based on the abnormally high concentration of mast cells in the skin. Systemic mastocytosis is diagnosed based on biopsy results showing an increased number of mast cells in an organ other than the skin. Plasma histamine or tryptase protein will be persistently elevated in people who have mastocytosis. Urine may also contain high levels of histamine metabolites or metabolites of prostaglandin D2. In addition, other tests may be used to diagnosis mastocytosis. Various drugs are used to treat mastocytosis, including antihistamines and anticholinergics. 2 figures.
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Causes of Dizziness Source: Portland, OR: Vestibular Disorders Association (VEDA). 199x. 4 p. Contact: Available from Vestibular Disorders Association (VEDA). P.O. Box 4467, Portland, OR 97208-4467. (503) 229-7705. Fax (503) 229-8064. E-mail:
[email protected]. Website: www.vestibular.org. PRICE: $0.50 plus shipping and handling. Order number S-9.
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Summary: This fact sheet summarizes the various causes of dizziness and vertigo. The author begins with a review of how patients tend to describe different types of dizziness, and then describes the possible causes for each type. The fact sheet discusses cardiovascular disorders and dizziness, including arrhythmia, embolism, heart attack, defective heart valve, aneurysm, orthostatic hypotension, hardening of the vertebral arteries, and slowness of the carotid sinus reflex. Other topics include vestibular disorders and dizziness and multiple sensory deficits. The author concludes with a brief discussion of the drug therapy available to treat dizziness. 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 “hypotension” (or synonyms). The following was recently posted: •
(1) Part I. Guidelines for the management of severe traumatic brain injury. In: Management and prognosis of severe traumatic brain injury. (2) Update notice. Guidelines for the management of severe traumatic brain injury: cerebral perfusion pressure Source: American Association of Neurological Surgeons - Medical Specialty Society; 2000 (revised 2003); 165 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3794&nbr=3020&a mp;string=hypotension
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1999 update: ACC/AHA guidelines for the management of patients with acute myocardial infarction. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Management of Acute Myocardial Infar Source: American College of Cardiology Foundation - Medical Specialty Society; 1996 November 1 (revised 1999 Sep); 22 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2006&nbr=1232&a mp;string=hypotension
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2002 update of recommendations for the use of chemotherapy and radiotherapy protectants: clinical practice guidelines of the American Society of Clinical Oncology Source: American Society of Clinical Oncology - Medical Specialty Society; 1999 October (revised 2002 Jun); 9 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3348&nbr=2574&a mp;string=hypotension
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A guideline for the management of heart failure Source: National Heart Foundation of New Zealand - Disease Specific Society; 1996 (revised 2001 Dec); 30 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3309&nbr=2535&a mp;string=hypotension
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AACE medical guidelines for clinical practice for the diagnosis and treatment of hyperandrogenic disorders Source: American Association of Clinical Endocrinologists - Medical Specialty Society; 2001 Mar-April; 15 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2847&nbr=2073&a mp;string=hypotension
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ACC/AHA 2002 guideline update for exercise testing. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Exercise Testing) Source: American College of Cardiology Foundation - Medical Specialty Society; 1997 July (revised 2002 Sep); 59 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3427&nbr=2653&a mp;string=hypotension
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ACC/AHA 2002 guideline update for the management of patients with chronic stable angina: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Update the 1999 Guidelines for the Managemen Source: American College of Cardiology Foundation - Medical Specialty Society; 1999 June (revised 2002); 127 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3588&nbr=2814&a mp;string=hypotension
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ACC/AHA 2002 guideline update for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Source: American College of Cardiology Foundation - Medical Specialty Society; 2000 (revised online 2002 Mar); 95 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3190&nbr=2416&a mp;string=hypotension
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ACC/AHA guideline update on perioperative cardiovascular evaluation for noncardiac surgery: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Update the 1996 Guidelines on Perioperati Source: American College of Cardiology Foundation - Medical Specialty Society; 1996 March 15 (revised 2002); 58 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3149&nbr=2375&a mp;string=hypotension
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ACC/AHA guidelines for the evaluation and management of chronic heart failure in the adult: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1995 Guidelines for the Evalua Source: American College of Cardiology Foundation - Medical Specialty Society; 1995 November 1 (revised 2001 Dec); 56 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3114&nbr=2340&a mp;string=hypotension
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ACC/AHA/ESC guidelines for the management of patients with atrial fibrillation. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guide Source: American College of Cardiology Foundation - Medical Specialty Society; 2001 October; 70 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2968&nbr=2194&a mp;string=hypotension
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ACR Appropriateness Criteriaâ„¢ for imaging of blunt abdominal trauma Source: American College of Radiology - Medical Specialty Society; 1996 (revised 1999); 9 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2401&nbr=1627&a mp;string=hypotension
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Acute management of autonomic dysreflexia: individuals with spinal cord injury presenting to health-care facilities Source: Consortium for Spinal Cord Medicine - Private Nonprofit Organization; 1997 February (updated 2001 Jul); 29 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2964&nbr=2190&a mp;string=hypotension
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Acute pain management Source: University of Iowa Gerontological Nursing Interventions Research Center, Research Dissemination Core - Academic Institution; 1997 (revised 1999 April 6); 38 pages http://www.guideline.gov/summary/summary.aspx?doc_id=1888&nbr=1114&a mp;string=hypotension
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American Association of Clinical Endocrinologists medical guidelines for clinical practice for the evaluation and treatment of male sexual dysfunction: a couple's problem--2003 update Source: American Association of Clinical Endocrinologists - Medical Specialty Society; 1998 (revised 2003); 19 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3725&nbr=2951&a mp;string=hypotension
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American Gastroenterological Association medical position statement: irritable bowel syndrome Source: American Gastroenterological Association - Medical Specialty Society; 1996 November 10 (revised 2002 Dec); 20 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3685&nbr=2911&a mp;string=hypotension
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American Gastroenterological Association medical position statement: nausea and vomiting Source: American Gastroenterological Association - Medical Specialty Society; 2000 May 21 (reviewed 2001); 2 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3060&nbr=2286&a mp;string=hypotension
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Angina pectoris and coronary artery disease (CAD) Source: Finnish Medical Society Duodecim - Professional Association; 2001 April 30 (revised 2003 October 5); Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=4372&nbr=3294&a mp;string=hypotension
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Antithrombotic therapy. A national clinical guideline Source: Scottish Intercollegiate Guidelines Network - National Government Agency [Non-U.S.]; 1999 March; 70 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2907&nbr=2133&a mp;string=hypotension
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Apnea of prematurity Source: National Association of Neonatal Nurses - Professional Association; 1999; 22 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2147&nbr=1373&a mp;string=hypotension
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ASHP therapeutic guidelines on the pharmacologic management of nausea and vomiting in adult and pediatric patients receiving chemotherapy or radiation therapy or undergoing surgery Source: American Society of Health-System Pharmacists - Professional Association; 1999; 36 pages http://www.guideline.gov/summary/summary.aspx?doc_id=1875&nbr=1101&a mp;string=hypotension
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Assessment and management of acute pain Source: Institute for Clinical Systems Improvement - Private Nonprofit Organization; 2000 October (revised 2002 Oct); 74 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3500&nbr=2726&a mp;string=hypotension
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Benign prostatic hyperplasia Source: Finnish Medical Society Duodecim - Professional Association; 2001 April 30 (revised 2002 March 22); Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3811&nbr=3037&a mp;string=hypotension
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Chemotherapy and biotherapy: guidelines and recommendations for practice Source: Oncology Nursing Society - Professional Association; 2001; 226 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3209&nbr=2435&a mp;string=hypotension
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Clinical practice guideline for the management of postoperative pain Source: Department of Defense - Federal Government Agency [U.S.]; 2001 July (revised 2002 May); Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3284&nbr=2510&a mp;string=hypotension
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Clinical practice guidelines for sustained neuromuscular blockade in the adult critically ill patient Source: American College of Critical Care Medicine - Professional Association; 1995 (revised 2002); 15 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3170&nbr=2396&a mp;string=hypotension
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Clinical practice guidelines for the sustained use of sedatives and analgesics in the critically ill adult Source: American College of Critical Care Medicine - Professional Association; 1995 (revised 2002); 23 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3171&nbr=2397&a mp;string=hypotension
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Clinical practice parameters for hemodynamic support of pediatric and neonatal patients in septic shock Source: American College of Critical Care Medicine - Professional Association; 2002 June; 14 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3433&nbr=2659&a mp;string=hypotension
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Congestive heart failure in adults Source: Institute for Clinical Systems Improvement - Private Nonprofit Organization; 1997 October (revised 2002 Jan); 71 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3165&nbr=2391&a mp;string=hypotension
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Control of pain in patients with cancer. A national clinical guideline Source: Scottish Intercollegiate Guidelines Network - National Government Agency [Non-U.S.]; 2000 June; 61 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2910&nbr=2136&a mp;string=hypotension
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Dementia Source: American Health Care Association - Professional Association; 1998 (reviewed 2003); 32 pages http://www.guideline.gov/summary/summary.aspx?doc_id=1805&nbr=1031&a mp;string=hypotension
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Diagnosis and management of achalasia Source: American College of Gastroenterology - Medical Specialty Society; 1999 December; 7 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2197&nbr=1423&a mp;string=hypotension
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Diagnosis and management of hypertension in the primary care setting Source: Department of Defense - Federal Government Agency [U.S.]; 1999 May; Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=2579&nbr=1805&a mp;string=hypotension
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Diagnosis and treatment of heart failure due to left ventricular systolic dysfunction. A national clinical guideline Source: Scottish Intercollegiate Guidelines Network - National Government Agency [Non-U.S.]; 1999 February; 68 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2906&nbr=2132&a mp;string=hypotension
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Diagnosis of chest pain Source: Institute for Clinical Systems Improvement - Private Nonprofit Organization; 1995 July (revised 2002 Oct); 50 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3674&nbr=2900&a mp;string=hypotension
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Differential diagnosis of chest pain Source: Finnish Medical Society Duodecim - Professional Association; 2001 May 4; Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=2852&nbr=2078&a mp;string=hypotension
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Essential hypertension Source: University of Michigan Health System - Academic Institution; 1997 (revised 2002 Aug); 14 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3539&nbr=2765&a mp;string=hypotension
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Evidence-based clinical practice guideline. Nursing care of the woman receiving regional analgesia/anesthesia in labor Source: Association of Women's Health, Obstetric, and Neonatal Nurses - Professional Association; 2001 January; 36 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2928&nbr=2154&a mp;string=hypotension
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Evidence-based guidelines for weaning and discontinuation of ventilatory support Source: American Association for Respiratory Care - Professional Association; 2001 December; 21 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3214&nbr=2440&a mp;string=hypotension
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General recommendations on immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP) and the American Academy of Family Physicians (AAFP) Source: American Academy of Family Physicians - Medical Specialty Society; 2002 February 8; 36 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3180&nbr=2406&a mp;string=hypotension
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Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease Source: National Heart, Lung, and Blood Institute (U.S.) - Federal Government Agency [U.S.]; 2001; Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=2779&nbr=2005&a mp;string=hypotension
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Guideline for the prevention of falls in older persons Source: American Academy of Orthopaedic Surgeons - Medical Specialty Society; 2001 May; 9 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2973&nbr=2199&a mp;string=hypotension
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Guidelines for Alzheimer's disease management. Source: Alzheimer's Association of Los Angeles, Riverside and San Bernardino Counties - Private Nonprofit Organization; 1999 January 8 (revised 2002 Jan 1); 52 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3157&nbr=2383&a mp;string=hypotension
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Guidelines for prehospital management of traumatic brain injury Source: Brain Trauma Foundation - Disease Specific Society; 2000; 81 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3288&nbr=2514&a mp;string=hypotension
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Guidelines for smoking cessation: revised 2002 Source: New Zealand Guidelines Group - Private Nonprofit Organization; 1999 July (revised 2002 May); 33 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3307&nbr=2533&a mp;string=hypotension
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Guidelines for the diagnosis and treatment of chronic heart failure Source: European Society of Cardiology - Medical Specialty Society; 2001 September; 34 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2976&nbr=2202&a mp;string=hypotension
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Guidelines for the prevention of falls in people over 65 Source: Barts and the London, Queen Mary's School of Medicine and Dentistry Academic Institution; 2000 October 21; 5 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2572&nbr=1798&a mp;string=hypotension
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Guidelines on diagnosis and management of acute pulmonary embolism Source: European Society of Cardiology - Medical Specialty Society; 2000 August; 36 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2592&nbr=1818&a mp;string=hypotension
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Guidelines on management (diagnosis and treatment) of syncope Source: European Society of Cardiology - Medical Specialty Society; 2001 August; 51 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2974&nbr=2200&a mp;string=hypotension
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Heart failure Source: American Medical Directors Association - Professional Association; 1996 (revised 2002); 18 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3303&nbr=2529&a mp;string=hypotension
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Heart Failure Society of America guidelines for management of patients with heart failure caused by left ventricular systolic dysfunction: pharmacological approaches Source: Heart Failure Society of America, Inc - Disease Specific Society; 1999 December; 36 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2736&nbr=1962&a mp;string=hypotension
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Hypertension Source: National Committee on Cardiac Care (Singapore) - National Government Agency [Non-U.S.]; 2000 December; 42 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2837&nbr=2063&a mp;string=hypotension
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In-hospital transport of the mechanically ventilated patient: 2002 revision and update Source: American Association for Respiratory Care - Professional Association; 1993 December (revised 2002 Jun); 3 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3247&nbr=2473&a mp;string=hypotension
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Major depression, panic disorder and generalized anxiety disorder in adults in primary care Source: Institute for Clinical Systems Improvement - Private Nonprofit Organization; 1996 January (revised 2002 May); 55 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3350&nbr=2576&a mp;string=hypotension
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Management of acute coronary syndromes in patients presenting without persistent ST- segment elevation Source: European Society of Cardiology - Medical Specialty Society; 2000 September (revised 2002 Dec); 32 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3518&nbr=2744&a mp;string=hypotension
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Management of acute myocardial infarction in patients presenting with ST-segment elevation Source: European Society of Cardiology - Medical Specialty Society; 1996 (revised 2003); 39 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3590&nbr=2816&a mp;string=hypotension
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Management of patients who have a history of penicillin allergy. Sexually transmitted diseases treatment guidelines 2002 Source: Centers for Disease Control and Prevention - Federal Government Agency [U.S.]; 1993 (revised 2002 May 10); 3 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3235&nbr=2461&a mp;string=hypotension
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Mealtime difficulties for older persons: assessment and management Source: The John A. Hartford Foundation Institute for Geriatric Nursing - Academic Institution; 2003; 23 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3506&nbr=2732&a mp;string=hypotension
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Myocardial infarction Source: Finnish Medical Society Duodecim - Professional Association; 2001 April 30 (revised 2003 July 11); Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=4373&nbr=3295&a mp;string=hypotension
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National High Blood Pressure Education Program: Working Group report on high blood pressure in pregnancy Source: National Heart, Lung, and Blood Institute (U.S.) - Federal Government Agency [U.S.]; 1990 (revised 2000 Jul); 39 pages http://www.guideline.gov/summary/summary.aspx?doc_id=1478&nbr=704&am p;string=hypotension
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NKF-K/DOQI clinical practice guidelines for anemia of chronic kidney disease: update 2000 Source: National Kidney Foundation - Disease Specific Society; 1997 (updated 2000); 67 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2784&nbr=2010&a mp;string=hypotension
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NKF-K/DOQI clinical practice guidelines for hemodialysis adequacy: update 2000 Source: National Kidney Foundation - Disease Specific Society; 1997 (updated 2000); 58 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2781&nbr=2007&a mp;string=hypotension
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Part II. Early indicators of prognosis in severe traumatic brain injury. In: Management and prognosis of severe traumatic brain injury Source: American Association of Neurological Surgeons - Medical Specialty Society; 2000; 116 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3122&nbr=2348&a mp;string=hypotension
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Pharmacologic treatment of acute major depression and dysthymia Source: American College of Physicians - Medical Specialty Society; 2000; 5 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2547&nbr=1773&a mp;string=hypotension
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Physical activity/exercise and diabetes mellitus Source: American College of Sports Medicine - Medical Specialty Society; 1990 February (revised 1999; republished 2003 Jan); 5 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3571&nbr=2797&a mp;string=hypotension
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Practice guideline for the treatment of patients with bipolar disorder (revision) Source: American Psychiatric Association - Medical Specialty Society; 1994 December (revised 2002 Apr); 50 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3302&nbr=2528&a mp;string=hypotension
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Practice guideline for the treatment of patients with borderline personality disorder Source: American Psychiatric Association - Medical Specialty Society; 2001 October; 52 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2972&nbr=2198&a mp;string=hypotension
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Practice guideline for the treatment of patients with eating disorders Source: American Psychiatric Association - Medical Specialty Society; 1993 (updated 2000 Jan); 51 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2194&nbr=1420&a mp;string=hypotension
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Practice guideline for the treatment of patients with major depressive disorder Source: American Psychiatric Association - Medical Specialty Society; 1993 (revised 2000); 45 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2605&nbr=1831&a mp;string=hypotension
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Practice guidelines for obstetrical anesthesia Source: American Society of Anesthesiologists - Medical Specialty Society; 1999; 11 pages http://www.guideline.gov/summary/summary.aspx?doc_id=1853&nbr=1079&a mp;string=hypotension
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Practice management guidelines for hemorrhage in pelvic fracture Source: Eastern Association for the Surgery of Trauma - Professional Association; 2001; 15 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2960&nbr=2186&a mp;string=hypotension
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Practice management guidelines for the optimal timing of long bone fracture stabilization in polytrauma patients Source: Eastern Association for the Surgery of Trauma - Professional Association; 2000; 39 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2795&nbr=2021&a mp;string=hypotension
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Practice parameter for the assessment and treatment of children and adolescents with schizophrenia Source: American Academy of Child and Adolescent Psychiatry - Medical Specialty Society; 2000 June 6; 40 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3017&nbr=2243&a mp;string=hypotension
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Practice parameters for the treatment of narcolepsy: an update for 2000. Source: American Academy of Sleep Medicine - Professional Association; 1994 (updated 2001 Jun); 16 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2933&nbr=2159&a mp;string=hypotension
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Prevention and management of pain and stress in the neonate Source: American Academy of Pediatrics - Medical Specialty Society; 2000 February; 8 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2597&nbr=1823&a mp;string=hypotension
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Preventive services for adults Source: Institute for Clinical Systems Improvement - Private Nonprofit Organization; 1995 June (revised 2002 Sep); 50 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3501&nbr=2727&a mp;string=hypotension
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Procedure guideline for brain perfusion single photon computed tomography (SPECT) using Tc-99m radiopharmaceuticals Source: Society of Nuclear Medicine, Inc - Medical Specialty Society; 1999 February; 22 pages http://www.guideline.gov/summary/summary.aspx?doc_id=1334&nbr=602&am p;string=hypotension
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Procedure guideline for diuretic renography in children Source: Society of Nuclear Medicine, Inc - Medical Specialty Society; 1999 February; 18 pages http://www.guideline.gov/summary/summary.aspx?doc_id=1357&nbr=615&am p;string=hypotension
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Procedure guideline for myocardial perfusion imaging Source: Society of Nuclear Medicine, Inc - Medical Specialty Society; 1999 February; 27 pages http://www.guideline.gov/summary/summary.aspx?doc_id=1353&nbr=611&am p;string=hypotension
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Recommendation for the management of stress and urge urinary incontinence in women Source: University of Texas at Austin School of Nursing, Family Nurse Practitioner Program - Academic Institution; 2002 May; 13 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3227&nbr=2453&a mp;string=hypotension
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Recommendations for the use of hematopoietic colony-stimulating factors: evidencebased, clinical practice guidelines Source: American Society of Clinical Oncology - Medical Specialty Society; 1994 November (updated 2000); 37 pages http://www.guideline.gov/summary/summary.aspx?doc_id=893&nbr=44& string=hypotension
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Schizophrenia Source: Singapore Ministry of Health - National Government Agency [Non-U.S.]; 2003 February; 40 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3750&nbr=2976&a mp;string=hypotension
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Smallpox vaccination and adverse reactions. Guidance for clinicians Source: Centers for Disease Control and Prevention - Federal Government Agency [U.S.]; 2003 January 24; 29 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3597&nbr=2823&a mp;string=hypotension
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Specialty referral guidelines for cardiovascular evaluation and management Source: American Healthways, Inc - Public For Profit Organization; 2002; 26 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3168&nbr=2394&a mp;string=hypotension
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Stable coronary artery disease Source: Institute for Clinical Systems Improvement - Private Nonprofit Organization; 1994 July (revised 2002 Jan); 32 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3158&nbr=2384&a mp;string=hypotension
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Suctioning of the patient in the home Source: American Association for Respiratory Care - Professional Association; 1999 January; 8 pages http://www.guideline.gov/summary/summary.aspx?doc_id=1769&nbr=995&am p;string=hypotension
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The American Association of Clinical Endocrinologists medical guidelines for the management of diabetes mellitus: the AACE system of intensive diabetes selfmanagement--2002 update Source: American Association of Clinical Endocrinologists - Medical Specialty Society; 2000 January (revised 2002 Jan); 43 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3172&nbr=2398&a mp;string=hypotension
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The management of benign prostatic hyperplasia Source: American Urological Association, Inc. - Medical Specialty Society; 2003; Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3740&nbr=2966&a mp;string=hypotension
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The management of diabetes mellitus in the primary care setting Source: Department of Defense - Federal Government Agency [U.S.]; 1999 December; 147 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2583&nbr=1809&a mp;string=hypotension
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The primary care management of erectile dysfunction Source: Department of Veterans Affairs - Federal Government Agency [U.S.]; 1999 June; 67 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2577&nbr=1803&a mp;string=hypotension
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The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure Source: National Heart, Lung, and Blood Institute (U.S.) - Federal Government Agency [U.S.]; 1997 (revised 2003 May 21); 22 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3744&nbr=2970&a mp;string=hypotension
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Treatment of acute myocardial infarction Source: Institute for Clinical Systems Improvement - Private Nonprofit Organization; 1996 May (revised 2002 Nov); 68 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3659&nbr=2885&a mp;string=hypotension
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Treatment of hypertension in adults with diabetes Source: American Diabetes Association - Professional Association; 2001 October (republished 2003 Jan); 3 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3573&nbr=2799&a mp;string=hypotension
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Universe of Florida patients with acute ischemic brain attack Source: Florida Agency for Health Care Administration - State/Local Government Agency [U.S.]; 1999 March 5; 16 pages http://www.guideline.gov/summary/summary.aspx?doc_id=1801&nbr=1027&a mp;string=hypotension
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Urinary incontinence Source: American Medical Directors Association - Professional Association; 1996 (reviewed January 2001, 2002 and 2003); 16 pages http://www.guideline.gov/summary/summary.aspx?doc_id=1812&nbr=1038&a mp;string=hypotension
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Use of amifostine to ameliorate the toxic effects of chemotherapy in the treatment of cancer Source: Practice Guidelines Initiative - State/Local Government Agency [Non-U.S.]; 1998 December 18 (updated online 2003 Jan); 19 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3703&nbr=2929&a mp;string=hypotension
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Use of antibiotics in paediatric care Source: Singapore Ministry of Health - National Government Agency [Non-U.S.]; 2002 March; 109 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3436&nbr=2662&a mp;string=hypotension
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Use of irinotecan in the treatment of metastatic colorectal carcinoma Source: Practice Guidelines Initiative - State/Local Government Agency [Non-U.S.]; 1999 April 30 (updated online 2000 Apr); Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3007&nbr=2233&a mp;string=hypotension
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VHA/DOD clinical practice guideline for the management of major depressive disorder in adults Source: Department of Defense - Federal Government Agency [U.S.]; 1997 (updated 2000); Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=2585&nbr=1811&a mp;string=hypotension
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VHA/DoD clinical practice guideline for the management of substance use disorders Source: Department of Defense - Federal Government Agency [U.S.]; 2001 September; Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3169&nbr=2395&a mp;string=hypotension 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 hypotension. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •
AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats
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Family Village: http://www.familyvillage.wisc.edu/specific.htm
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Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/
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Med Help International: http://www.medhelp.org/HealthTopics/A.html
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Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/
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Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/
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WebMD®Health: http://my.webmd.com/health_topics
Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to hypotension. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with hypotension. 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 hypotension. For more information, see
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the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797. Directory of Health Organizations The Directory of Health Organizations, provided by the National Library of Medicine Specialized Information Services, is a comprehensive source of information on associations. The Directory of Health Organizations database can be accessed via the Internet at http://www.sis.nlm.nih.gov/Dir/DirMain.html. It is composed of two parts: DIRLINE and Health Hotlines. The DIRLINE database comprises some 10,000 records of organizations, research centers, and government institutes and associations that primarily focus on health and biomedicine. To access DIRLINE directly, go to the following Web site: http://dirline.nlm.nih.gov/. Simply type in “hypotension” (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 “hypotension”. 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 “hypotension” (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 “hypotension” (or a synonym) into the search box, and click “Submit Query.”
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APPENDIX C. FINDING MEDICAL LIBRARIES Overview In this Appendix, we show you how to quickly find a medical library in your area.
Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.25
Finding a Local Medical Library The quickest method to locate medical libraries is to use the Internet-based directory published by the National Network of Libraries of Medicine (NN/LM). This network includes 4626 members and affiliates that provide many services to librarians, health professionals, and the public. To find a library in your area, simply visit http://nnlm.gov/members/adv.html or call 1-800-338-7657.
Medical Libraries in the U.S. and Canada In addition to the NN/LM, the National Library of Medicine (NLM) lists a number of libraries with reference facilities that are open to the public. The following is the NLM’s list and includes hyperlinks to each library’s Web site. These Web pages can provide information on hours of operation and other restrictions. The list below is a small sample of
25
Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.
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libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)26: •
Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/
•
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/
26
Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.
Finding Medical Libraries 209 •
Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml
•
Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm
•
Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html
•
Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm
•
Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp
•
Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/
•
Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm
•
Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html
•
Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/
•
Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm
•
Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/
•
Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/
•
Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/
•
Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm
•
Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html
•
Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm
•
Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/
•
Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/
•
Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10
•
Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/
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•
Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html
•
Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp
•
Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp
•
Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/
•
Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html
•
Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm
•
Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp
•
Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/
•
Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html
•
Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/
•
Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm
•
Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/
•
Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html
•
Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm
•
Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330
•
Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)
•
National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html
•
National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/
•
National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/
Finding Medical Libraries 211 •
Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm
•
New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/
•
New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm
•
New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm
•
New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/
•
New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html
•
New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/
•
New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html
•
New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/
•
Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm
•
Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp
•
Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/
•
Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/
•
Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml
•
Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html
•
Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html
•
Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml
•
Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp
•
Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm
•
Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/
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•
South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp
•
Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/
•
Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/
•
Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72
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ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •
ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html
•
MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp
•
Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/
•
Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html
•
On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/
•
Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp
•
Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm
Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a).
Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •
Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical
•
MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html
•
Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/
•
Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine
215
HYPOTENSION 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] Abducens: A striated, extrinsic muscle of the eyeball that originates from the annulus of Zinn. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] 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] Acclimation: Adaptation of animals or plants to new climate. [NIH] Accommodation: Adjustment, especially that of the eye for various distances. [EU] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Acidosis: A pathologic condition resulting from accumulation of acid or depletion of the alkaline reserve (bicarbonate content) in the blood and body tissues, and characterized by an increase in hydrogen ion concentration. [EU] Acoustic: Having to do with sound or hearing. [NIH] Actin: Essential component of the cell skeleton. [NIH] Acute renal: A condition in which the kidneys suddenly stop working. In most cases, kidneys can recover from almost complete loss of function. [NIH] Acute tubular: A severe form of acute renal failure that develops in people with severe illnesses like infections or with low blood pressure. Patients may need dialysis. Kidney function often improves if the underlying disease is successfully treated. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adaptation: 1. The adjustment of an organism to its environment, or the process by which it enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the intensity of light; the adjustment to such variations. 3. The decline in the frequency of firing of a neuron, particularly of a receptor, under conditions of constant stimulation. 4. In dentistry, (a) the proper fitting of a denture, (b) the degree of proximity and interlocking of restorative material to a tooth preparation, (c) the exact adjustment of bands to teeth. 5. In microbiology, the adjustment of bacterial physiology to a new environment. [EU] Adenine: A purine base and a fundamental unit of adenine nucleotides. [NIH]
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Adenocarcinoma: A malignant epithelial tumor with a glandular organization. [NIH] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adenylate Cyclase: An enzyme of the lyase class that catalyzes the formation of cyclic AMP and pyrophosphate from ATP. EC 4.6.1.1. [NIH] Adipocytes: Fat-storing cells found mostly in the abdominal cavity and subcutaneous tissue. Fat is usually stored in the form of tryglycerides. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adolescence: The period of life beginning with the appearance of secondary sex characteristics and terminating with the cessation of somatic growth. The years usually referred to as adolescence lie between 13 and 18 years of age. [NIH] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH] Adrenal Glands: Paired glands situated in the retroperitoneal tissues at the superior pole of each kidney. [NIH] Adrenal 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] Adrenergic Uptake Inhibitors: Drugs that block the transport of adrenergic transmitters into axon terminals or into storage vesicles within terminals. The tricyclic antidepressants (antidepressive agents, tricyclic) and amphetamines are among the therapeutically important drugs that may act via inhibition of adrenergic transport. Many of these drugs also block transport of serotonin. [NIH] Adrenoreceptor: Receptors specifically sensitive to and operated by adrenaline and/or noradrenaline and related sympathomimetic drugs. Adrenoreceptor is an alternative name. [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
Dictionary 217
that can improve cardiorespiratory endurance. [NIH] Aerosol: A solution of a drug which can be atomized into a fine mist for inhalation therapy. [EU]
Afferent: Concerned with the transmission of neural impulse toward the central part of the nervous system. [NIH] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Agar: A complex sulfated polymer of galactose units, extracted from Gelidium cartilagineum, Gracilaria confervoides, and related red algae. It is used as a gel in the preparation of solid culture media for microorganisms, as a bulk laxative, in making emulsions, and as a supporting medium for immunodiffusion and immunoelectrophoresis. [NIH]
Age of Onset: The age or period of life at which a disease or the initial symptoms or manifestations of a disease appear in an individual. [NIH] Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Agoraphobia: Obsessive, persistent, intense fear of open places. [NIH] Air Embolism: Occurs when the lungs over expand to the point that air bubbles are forced through the air sacs of the lungs into the circulatory system. [NIH] 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] Airway Obstruction: Any hindrance to the passage of air into and out of the lungs. [NIH] Albumin: 1. Any protein that is soluble in water and moderately concentrated salt solutions and is coagulable by heat. 2. Serum albumin; the major plasma protein (approximately 60 per cent of the total), which is responsible for much of the plasma colloidal osmotic pressure and serves as a transport protein carrying large organic anions, such as fatty acids, bilirubin, and many drugs, and also carrying certain hormones, such as cortisol and thyroxine, when their specific binding globulins are saturated. Albumin is synthesized in the liver. Low serum levels occur in protein malnutrition, active inflammation and serious hepatic and renal disease. [EU] 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] Alertness: A state of readiness to detect and respond to certain specified small changes occurring at random intervals in the environment. [NIH]
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Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alimentary: Pertaining to food or nutritive material, or to the organs of digestion. [EU] Alkaline: Having the reactions of an alkali. [EU] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Allergens: Antigen-type substances (hypersensitivity, immediate). [NIH]
that
produce
immediate
hypersensitivity
Alopecia: Absence of hair from areas where it is normally present. [NIH] Alpha Particles: Positively charged particles composed of two protons and two neutrons, i.e., helium nuclei, emitted during disintegration of very heavy isotopes; a beam of alpha particles or an alpha ray has very strong ionizing power, but weak penetrability. [NIH] Alpha-1: A protein with the property of inactivating proteolytic enzymes such as leucocyte collagenase and elastase. [NIH] Alternans: Ipsilateral abducens palsy and facial paralysis and contralateral hemiplegia of the limbs, due to a nuclear or infranuclear lesion in the pons. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Alveolitis: Inflammation of an alveolus. Called also odontobothritis. [EU] Amaurosis: Partial or total blindness from any cause. [NIH] Amaurosis Fugax: Partial amaurosis, which is sudden and transitory, and associated with headache, vertigo, and nausea. [NIH] Ameliorating: A changeable condition which prevents the consequence of a failure or accident from becoming as bad as it otherwise would. [NIH] Amenorrhea: Absence of menstruation. [NIH] Amifostine: A phosphorothioate proposed as a radiation-protective agent. It causes splenic vasodilation and may block autonomic ganglia. [NIH] Amine: An organic compound containing nitrogen; any member of a group of chemical compounds formed from ammonia by replacement of one or more of the hydrogen atoms by organic (hydrocarbon) radicals. The amines are distinguished as primary, secondary, and tertiary, according to whether one, two, or three hydrogen atoms are replaced. The amines include allylamine, amylamine, ethylamine, methylamine, phenylamine, propylamine, and many other compounds. [EU] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino Acid Substitution: The naturally occurring or experimentally induced replacement of one or more amino acids in a protein with another. If a functionally equivalent amino acid is substituted, the protein may retain wild-type activity. Substitution may also diminish or eliminate protein function. Experimentally induced substitution is often used to study
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enzyme activities and binding site properties. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. [NIH] Amnesia: Lack or loss of memory; inability to remember past experiences. [EU] Amniotic Fluid: Amniotic cavity fluid which is produced by the amnion and fetal lungs and kidneys. [NIH] Amplification: The production of additional copies of a chromosomal DNA sequence, found as either intrachromosomal or extrachromosomal DNA. [NIH] Ampulla: A sac-like enlargement of a canal or duct. [NIH] Amputation: Surgery to remove part or all of a limb or appendage. [NIH] Amyloid: A general term for a variety of different proteins that accumulate as extracellular fibrils of 7-10 nm and have common structural features, including a beta-pleated sheet conformation and the ability to bind such dyes as Congo red and thioflavine (Kandel, Schwartz, and Jessel, Principles of Neural Science, 3rd ed). [NIH] Amyloidosis: A group of diseases in which protein is deposited in specific organs (localized amyloidosis) or throughout the body (systemic amyloidosis). Amyloidosis may be either primary (with no known cause) or secondary (caused by another disease, including some types of cancer). Generally, primary amyloidosis affects the nerves, skin, tongue, joints, heart, and liver; secondary amyloidosis often affects the spleen, kidneys, liver, and adrenal glands. [NIH] Anaemia: A reduction below normal in the number of erythrocytes per cu. mm., in the quantity of haemoglobin, or in the volume of packed red cells per 100 ml. of blood which occurs when the equilibrium between blood loss (through bleeding or destruction) and blood production is disturbed. [EU] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU] 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] 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
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distress, vascular collapse, systemic shock, and death. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Androgens: A class of sex hormones associated with the development and maintenance of the secondary male sex characteristics, sperm induction, and sexual differentiation. In addition to increasing virility and libido, they also increase nitrogen and water retention and stimulate skeletal growth. [NIH] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anergy: Absence of immune response to particular substances. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Anesthetics: Agents that are capable of inducing a total or partial loss of sensation, especially tactile sensation and pain. They may act to induce general anesthesia, in which an unconscious state is achieved, or may act locally to induce numbness or lack of sensation at a targeted site. [NIH] Aneurysm: A sac formed by the dilatation of the wall of an artery, a vein, or the heart. [NIH] Angina: Chest pain that originates in the heart. [NIH] Angina Pectoris: The symptom of paroxysmal pain consequent to myocardial ischemia usually of distinctive character, location and radiation, and provoked by a transient stressful situation during which the oxygen requirements of the myocardium exceed the capacity of the coronary circulation to supply it. [NIH] Angiogenesis: Blood vessel formation. Tumor angiogenesis is the growth of blood vessels from surrounding tissue to a solid tumor. This is caused by the release of chemicals by the tumor. [NIH] Angiography: Radiography of blood vessels after injection of a contrast medium. [NIH] Angiopathy: Disease of the blood vessels (arteries, veins, and capillaries) that occurs when someone has diabetes for a long time. There are two types of angiopathy: macroangiopathy and microangiopathy. In macroangiopathy, fat and blood clots build up in the large blood vessels, stick to the vessel walls, and block the flow of blood. In microangiopathy, the walls of the smaller blood vessels become so thick and weak that they bleed, leak protein, and slow the flow of blood through the body. Then the cells, for example, the ones in the center of the eye, do not get enough blood and may be damaged. [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 Inhibitors: A class of drugs whose main indications are the treatment of hypertension and heart failure. They exert their hemodynamic effect mainly by inhibiting the renin-angiotensin system. They also modulate sympathetic nervous system activity and increase prostaglandin synthesis. They cause mainly vasodilation and mild natriuresis without affecting heart rate and contractility. [NIH] Angiotensinogen: An alpha-globulin of which a fragment of 14 amino acids is converted by renin to angiotensin I, the inactive precursor of angiotensin II. It is a member of the serpin superfamily. [NIH] Animal model: An animal with a disease either the same as or like a disease in humans.
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Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Ankle: That part of the lower limb directly above the foot. [NIH] Annealing: The spontaneous alignment of two single DNA strands to form a double helix. [NIH]
Anomalies: Birth defects; abnormalities. [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] Anorexia Nervosa: The chief symptoms are inability to eat, weight loss, and amenorrhea. [NIH]
Anoxia: Clinical manifestation of respiratory distress consisting of a relatively complete absence of oxygen. [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] Antiallergic: Counteracting allergy or allergic conditions. [EU] Antiarrhythmic: An agent that prevents or alleviates cardiac arrhythmia. [EU] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]
Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Anticholinergic: An agent that blocks the parasympathetic nerves. Called also parasympatholytic. [EU] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Antidepressant: A drug used to treat depression. [NIH] Antidote: A remedy for counteracting a poison. [EU] Antiemetic: An agent that prevents or alleviates nausea and vomiting. Also antinauseant. [EU]
Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the
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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-infective: An agent that so acts. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are highly reactive chemicals that often contain oxygen. They are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation. [NIH] Antipruritic: Relieving or preventing itching. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU] Anuria: Inability to form or excrete urine. [NIH] Anus: The opening of the rectum to the outside of the body. [NIH] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Anxiety Disorders: Disorders in which anxiety (persistent feelings of apprehension, tension, or uneasiness) is the predominant disturbance. [NIH] Anxiolytic: An anxiolytic or antianxiety agent. [EU] Aorta: The main trunk of the systemic arteries. [NIH] Apathy: Lack of feeling or emotion; indifference. [EU] Apnea: A transient absence of spontaneous respiration. [NIH] Apolipoproteins: The protein components of lipoproteins which remain after the lipids to which the proteins are bound have been removed. They play an important role in lipid transport and metabolism. [NIH] Aponeurosis: Tendinous expansion consisting of a fibrous or membranous sheath which serves as a fascia to enclose or bind a group of muscles. [NIH] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Applicability: A list of the commodities to which the candidate method can be applied as presented or with minor modifications. [NIH] Aqueous: Having to do with water. [NIH] Aqueous humor: Clear, watery fluid that flows between and nourishes the lens and the cornea; secreted by the ciliary processes. [NIH] Arachidonic Acid: An unsaturated, essential fatty acid. It is found in animal and human fat
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as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Aromatic: Having a spicy odour. [EU] Arrhythmia: Any variation from the normal rhythm or rate of the heart beat. [NIH] 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] 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] Aspartate: A synthetic amino acid. [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] Ataxia: Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharnyx, larnyx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. [NIH] Atherectomy: Endovascular procedure in which atheromatous plaque is excised by a cutting or rotating catheter. It differs from balloon and laser angioplasty procedures which enlarge vessels by dilation but frequently do not remove much plaque. If the plaque is removed by surgical excision under general anesthesia rather than by an endovascular procedure through a catheter, it is called endarterectomy. [NIH] Atrial: Pertaining to an atrium. [EU] Atrial Fibrillation: Disorder of cardiac rhythm characterized by rapid, irregular atrial impulses and ineffective atrial contractions. [NIH] Atrioventricular: Pertaining to an atrium of the heart and to a ventricle. [EU] Atrium: A chamber; used in anatomical nomenclature to designate a chamber affording entrance to another structure or organ. Usually used alone to designate an atrium of the heart. [EU]
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Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] Atropine: A toxic alkaloid, originally from Atropa belladonna, but found in other plants, mainly Solanaceae. [NIH] Attenuated: Strain with weakened or reduced virulence. [NIH] Attenuation: Reduction of transmitted sound energy or its electrical equivalent. [NIH] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] Auditory: Pertaining to the sense of hearing. [EU] Autodigestion: Autolysis; a condition found in disease of the stomach: the stomach wall is digested by the gastric juice. [NIH] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Autoimmunity: Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by autoimmune diseases. [NIH] Autonomic: Self-controlling; functionally independent. [EU] Autonomic Denervation: The removal or interruption of some part of the autonomic nervous system for therapeutic or research purposes. [NIH] Autonomic Dysreflexia: That part of the nervous system concerned with the unconscious regulation of the living processes of the body. [NIH] Autonomic Nervous System: The enteric, parasympathetic, and sympathetic nervous systems taken together. Generally speaking, the autonomic nervous system regulates the internal environment during both peaceful activity and physical or emotional stress. Autonomic activity is controlled and integrated by the central nervous system, especially the hypothalamus and the solitary nucleus, which receive information relayed from visceral afferents; these and related central and sensory structures are sometimes (but not here) considered to be part of the autonomic nervous system itself. [NIH] Autonomic Neuropathy: A disease of the nerves affecting mostly the internal organs such as the bladder muscles, the cardiovascular system, the digestive tract, and the genital organs. These nerves are not under a person's conscious control and function automatically. Also called visceral neuropathy. [NIH] Autoradiography: A process in which radioactive material within an object produces an image when it is in close proximity to a radiation sensitive emulsion. [NIH] Axillary: Pertaining to the armpit area, including the lymph nodes that are located there. [NIH]
Axons: Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body. [NIH] Babesiosis: A group of tick-borne diseases of mammals including zoonoses in humans. They are caused by protozoans of the genus babesia, which parasitize erythrocytes, producing hemolysis. In the U.S., the organism's natural host is mice and transmission is by the deer tick ixodes scapularis. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacterial Infections: Infections by bacteria, general or unspecified. [NIH]
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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] Barbiturate: A drug with sedative and hypnotic effects. Barbiturates have been used as sedatives and anesthetics, and they have been used to treat the convulsions associated with epilepsy. [NIH] Baroreflex: A negative feedback system which buffers short-term changes in blood pressure. Increased pressure stretches blood vessels which activates pressoreceptors (baroreceptors) in the vessel walls. The net response of the central nervous system is a reduction of central sympathetic outflow. This reduces blood pressure both by decreasing peripheral vascular resistance and by lowering cardiac output. Because the baroreceptors are tonically active, the baroreflex can compensate rapidly for both increases and decreases in blood pressure. [NIH]
Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] Basal Ganglia Diseases: Diseases of the basal ganglia including the putamen; globus pallidus; claustrum; amygdala; and caudate nucleus. Dyskinesias (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include cerebrovascular disease; neurodegenerative diseases; and craniocerebral trauma. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Bed Rest: Confinement of an individual to bed for therapeutic or experimental reasons. [NIH] Belladonna: A species of very poisonous Solanaceous plants yielding atropine (hyoscyamine), scopolamine, and other belladonna alkaloids, used to block the muscarinic autonomic nervous system. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]
Benign prostatic hyperplasia: A benign (noncancerous) condition in which an overgrowth of prostate tissue pushes against the urethra and the bladder, blocking the flow of urine. Also called benign prostatic hypertrophy or BPH. [NIH] Benzene: Toxic, volatile, flammable liquid hydrocarbon biproduct of coal distillation. It is used as an industrial solvent in paints, varnishes, lacquer thinners, gasoline, etc. Benzene causes central nervous system damage acutely and bone marrow damage chronically and is carcinogenic. It was formerly used as parasiticide. [NIH] Benzodiazepines: A two-ring heterocyclic compound consisting of a benzene ring fused to a diazepine ring. Permitted is any degree of hydrogenation, any substituents and any Hisomer. [NIH] Beta 2-Microglobulin: An 11 kDa protein associated with the outer membrane of many cells including lymphocytes. It is the small subunit of the MHC class I molecule. Association with
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beta 2-microglobulin is generally required for the transport of class I heavy chains from the endoplasmic reticulum to the cell surface. Beta 2-microglobulin is present in small amounts in serum, csf, and urine of normal people, and to a much greater degree in the urine and plasma of patients with tubular proteinemia, renal failure, or kidney transplants. [NIH] Beta blocker: A drug used to slow the heart rate and reduce pressure inside blood vessels. It also can regulate heart rhythm. [NIH] Beta-Thromboglobulin: A platelet-specific protein which is released when platelets aggregate. Elevated plasma levels have been reported after deep venous thrombosis, preeclampsia, myocardial infarction with mural thrombosis, and myeloproliferative disorders. Measurement of beta-thromboglobulin in biological fluids by radioimmunoassay is used for the diagnosis and assessment of progress of thromboembolic disorders. [NIH] Bewilderment: Impairment or loss of will power. [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 Pigments: Pigments that give a characteristic color to bile including: bilirubin, biliverdine, and bilicyanin. [NIH] Biliary: Having to do with the liver, bile ducts, and/or gallbladder. [NIH] Biliary Tract: The gallbladder and its ducts. [NIH] Bilirubin: A bile pigment that is a degradation product of heme. [NIH] Binding Sites: The reactive parts of a macromolecule that directly participate in its specific combination with another molecule. [NIH] Bioassays: Determination of the relative effective strength of a substance (as a vitamin, hormone, or drug) by comparing its effect on a test organism with that of a standard preparation. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biological response modifier: BRM. A substance that stimulates the body's response to infection and disease. [NIH] Biological 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] Biological Transport: The movement of materials (including biochemical substances and drugs) across cell membranes and epithelial layers, usually by passive diffusion. [NIH] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Biopterin: A natural product that has been considered as a growth factor for some insects. [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
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technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Biotransformation: The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alteration may be either nonsynthetic (oxidation-reduction, hydrolysis) or synthetic (glucuronide formation, sulfate conjugation, acetylation, methylation). This also includes metabolic detoxication and clearance. [NIH] Biphasic: Having two phases; having both a sporophytic and a gametophytic phase in the life cycle. [EU] Bipolar Disorder: A major affective disorder marked by severe mood swings (manic or major depressive episodes) and a tendency to remission and recurrence. [NIH] Bladder: The organ that stores urine. [NIH] Blastocyst: The mammalian embryo in the post-morula stage in which a fluid-filled cavity, enclosed primarily by trophoblast, contains an inner cell mass which becomes the embryonic disc. [NIH] 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 Flow Velocity: A value equal to the total volume flow divided by the cross-sectional area of the vascular bed. [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 transfusion: The administration of blood or blood products into a blood vessel. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blood Viscosity: The internal resistance of the blood to shear forces. The in vitro measure of whole blood viscosity is of limited clinical utility because it bears little relationship to the actual viscosity within the circulation, but an increase in the viscosity of circulating blood can contribute to morbidity in patients suffering from disorders such as sickle cell anemia and polycythemia. [NIH] Blood Volume: Volume of circulating blood. It is the sum of the plasma volume and erythrocyte volume. [NIH] Blood-Aqueous Barrier: The selectively permeable barrier between the capillary bed in the ciliary body and the aqueous humor. It consists of two layers of epithelium joined at their apical surfaces by tight junctions. [NIH] Blood-Brain Barrier: Specialized non-fenestrated tightly-joined endothelial cells (tight junctions) that form a transport barrier for certain substances between the cerebral
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capillaries and the brain tissue. [NIH] Blood-Retinal Barrier: Specialized nonfenestrated tightly-joined endothelial cells that form a transport barrier for certain substances between the retinal capillaries and the retinal tissue. [NIH] Body Composition: The relative amounts of various components in the body, such as percent body fat. [NIH] Body Fluids: Liquid components of living organisms. [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] Bolus injection: The injection of a drug (or drugs) in a high quantity (called a bolus) at once, the opposite of gradual administration (as in intravenous infusion). [EU] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone metastases: Cancer that has spread from the original (primary) tumor to the bone. [NIH]
Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] Brachial: All the nerves from the arm are ripped from the spinal cord. [NIH] Brachial Artery: The continuation of the axillary artery; it branches into the radial and ulnar arteries. [NIH] 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] Brachytherapy: A collective term for interstitial, intracavity, and surface radiotherapy. It uses small sealed or partly-sealed sources that may be placed on or near the body surface or within a natural body cavity or implanted directly into the tissues. [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 Neoplasms: Neoplasms of the intracranial components of the central nervous system, including the cerebral hemispheres, basal ganglia, hypothalamus, thalamus, brain stem, and cerebellum. Brain neoplasms are subdivided into primary (originating from brain tissue)
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and secondary (i.e., metastatic) forms. Primary neoplasms are subdivided into benign and malignant forms. In general, brain tumors may also be classified by age of onset, histologic type, or presenting location in the brain. [NIH] Brain Stem: The part of the brain that connects the cerebral hemispheres with the spinal cord. It consists of the mesencephalon, pons, and medulla oblongata. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]
Breakdown: A physical, metal, or nervous collapse. [NIH] Breast Feeding: The nursing of an infant at the mother's breast. [NIH] Bronchi: The larger air passages of the lungs arising from the terminal bifurcation of the trachea. [NIH] Bronchial: Pertaining to one or more bronchi. [EU] Bronchiseptica: A small, gram-negative, motile bacillus. A normal inhabitant of the respiratory tract in man, dogs, and pigs, but is also associated with canine infectious tracheobronchitis and atrophic rhinitis in pigs. [NIH] Bronchitis: Inflammation (swelling and reddening) of the bronchi. [NIH] Bronchodilator: A drug that relaxes the smooth muscles in the constricted airway. [NIH] Bronchospasm: Spasmodic contraction of the smooth muscle of the bronchi, as occurs in asthma. [EU] Buffers: A chemical system that functions to control the levels of specific ions in solution. When the level of hydrogen ion in solution is controlled the system is called a pH buffer. [NIH]
Bulimia: Episodic binge eating. The episodes may be associated with the fear of not being able to stop eating, depressed mood, or self-deprecating thoughts (binge-eating disorder) and may frequently be terminated by self-induced vomiting (bulimia nervosa). [NIH] Buspirone: An anxiolytic agent and a serotonin receptor agonist belonging to the azaspirodecanedione class of compounds. Its structure is unrelated to those of the benzodiazepines, but it has an efficacy comparable to diazepam. [NIH] Cachexia: General ill health, malnutrition, and weight loss, usually associated with chronic disease. [NIH] Caesarean section: A surgical incision through the abdominal and uterine walls in order to deliver a baby. [NIH] Calcification: Deposits of calcium in the tissues of the breast. Calcification in the breast can be seen on a mammogram, but cannot be detected by touch. There are two types of breast calcification, macrocalcification and microcalcification. Macrocalcifications are large deposits and are usually not related to cancer. Microcalcifications are specks of calcium that may be found in an area of rapidly dividing cells. Many microcalcifications clustered together may be a sign of cancer. [NIH] Calcineurin: A calcium- and calmodulin-binding protein present in highest concentrations in the central nervous system. Calcineurin is composed of two subunits. A catalytic subunit, calcineurin A, and a regulatory subunit, calcineurin B, with molecular weights of about 60 kD and 19 kD, respectively. Calcineurin has been shown to dephosphorylate a number of phosphoproteins including histones, myosin light chain, and the regulatory subunit of cAMP-dependent protein kinase. It is involved in the regulation of signal transduction and is the target of an important class of immunophilin-immunosuppressive drug complexes in T-lymphocytes that act by inhibiting T-cell activation. EC 3.1.3.-. [NIH]
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Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Calcium channel blocker: A drug used to relax the blood vessel and heart muscle, causing pressure inside blood vessels to drop. It also can regulate heart rhythm. [NIH] Calcium Channel Blockers: A class of drugs that act by selective inhibition of calcium influx through cell membranes or on the release and binding of calcium in intracellular pools. Since they are inducers of vascular and other smooth muscle relaxation, they are used in the drug therapy of hypertension and cerebrovascular spasms, as myocardial protective agents, and in the relaxation of uterine spasms. [NIH] Calcium Channels: Voltage-dependent cell membrane glycoproteins selectively permeable to calcium ions. They are categorized as L-, T-, N-, P-, Q-, and R-types based on the activation and inactivation kinetics, ion specificity, and sensitivity to drugs and toxins. The L- and T-types are present throughout the cardiovascular and central nervous systems and the N-, P-, Q-, & R-types are located in neuronal tissue. [NIH] Calculi: An abnormal concretion occurring mostly in the urinary and biliary tracts, usually composed of mineral salts. Also called stones. [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] Caloric intake: Refers to the number of calories (energy content) consumed. [NIH] Camphor: A bicyclic monoterpene ketone found widely in plant (primarily the camphor tree, Cinnamomum camphora). Natural camphor is used topically as a skin antipruritic and as an anti-infective agent. [NIH] Camptothecin: An alkaloid isolated from the stem wood of the Chinese tree, Camptotheca acuminata. This compound selectively inhibits the nuclear enzyme DNA topoisomerase. Several semisynthetic analogs of camptothecin have demonstrated antitumor activity. [NIH] Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU] Capillary Permeability: Property of blood capillary walls that allows for the selective exchange of substances. Small lipid-soluble molecules such as carbon dioxide and oxygen move freely by diffusion. Water and water-soluble molecules cannot pass through the endothelial walls and are dependent on microscopic pores. These pores show narrow areas (tight junctions) which may limit large molecule movement. [NIH] Capsaicin: Cytotoxic alkaloid from various species of Capsicum (pepper, paprika), of the Solanaceae. [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]
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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] Carcinogenesis: The process by which normal cells are transformed into cancer cells. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinogens: Substances that increase the risk of neoplasms in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included. [NIH] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]
Cardiac: Having to do with the heart. [NIH] Cardiac arrest: A sudden stop of heart function. [NIH] Cardiac Output: The volume of blood passing through the heart per unit of time. It is usually expressed as liters (volume) per minute so as not to be confused with stroke volume (volume per beat). [NIH] Cardiogenic: Originating in the heart; caused by abnormal function of the heart. [EU] 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] Cardiopulmonary: Having to do with the heart and lungs. [NIH] Cardiopulmonary Bypass: Diversion of the flow of blood from the entrance of the right atrium directly to the aorta (or femoral artery) via an oxygenator thus bypassing both the heart and lungs. [NIH] Cardiopulmonary Resuscitation: The artificial substitution of heart and lung action as indicated for heart arrest resulting from electric shock, drowning, respiratory arrest, or other causes. The two major components of cardiopulmonary resuscitation are artificial ventilation and closed-chest cardiac massage. [NIH] Cardiopulmonary Resuscitation: The artificial substitution of heart and lung action as indicated for heart arrest resulting from electric shock, drowning, respiratory arrest, or other causes. The two major components of cardiopulmonary resuscitation are artificial ventilation and closed-chest cardiac massage. [NIH] Cardiorespiratory: Relating to the heart and lungs and their function. [EU] Cardiotonic: 1. Having a tonic effect on the heart. 2. An agent that has a tonic effect on the heart. [EU] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular Agents: Agents that affect the rate or intensity of cardiac contraction, blood vessel diameter, or blood volume. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] Cardiovascular Physiology: Functions and activities of the cardiovascular system as a whole or of any of its parts. [NIH] Cardiovascular System: The heart and the blood vessels by which blood is pumped and circulated through the body. [NIH]
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Carnitine: Constituent of striated muscle and liver. It is used therapeutically to stimulate gastric and pancreatic secretions and in the treatment of hyperlipoproteinemias. [NIH] Carotene: The general name for a group of pigments found in green, yellow, and leafy vegetables, and yellow fruits. The pigments are fat-soluble, unsaturated aliphatic hydrocarbons functioning as provitamins and are converted to vitamin A through enzymatic processes in the intestinal wall. [NIH] Carotid Body: A small cluster of chemoreceptive and supporting cells located near the bifurcation of the internal carotid artery. The carotid body, which is richly supplied with fenestrated capillaries, senses the pH, carbon dioxide, and oxygen concentrations in the blood and plays a crucial role in their homeostatic control. [NIH] Carotid Sinus: The dilated portion of the common carotid artery at its bifurcation into external and internal carotids. It contains baroreceptors which, when stimulated, cause slowing of the heart, vasodilatation, and a fall in blood pressure. [NIH] Carotid Stenosis: The constriction or narrowing of an orifice or the lumen of a hollow or tubular organ. [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] Catechols: A group of 1,2-benzenediols that contain the general formula R-C6H5O2. [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] Cathode: An electrode, usually an incandescent filament of tungsten, which emits electrons in an X-ray tube. [NIH] Cations: Postively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis. [NIH] Caudal: Denoting a position more toward the cauda, or tail, than some specified point of reference; same as inferior, in human anatomy. [EU] Causal: Pertaining to a cause; directed against a cause. [EU] Causality: The relating of causes to the effects they produce. Causes are termed necessary when they must always precede an effect and sufficient when they initiate or produce an effect. Any of several factors may be associated with the potential disease causation or outcome, including predisposing factors, enabling factors, precipitating factors, reinforcing
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factors, and risk factors. [NIH] Cause of Death: Factors which produce cessation of all vital bodily functions. They can be analyzed from an epidemiologic viewpoint. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Adhesion: Adherence of cells to surfaces or to other cells. [NIH] Cell Aggregation: The phenomenon by which dissociated cells intermixed in vitro tend to group themselves with cells of their own type. [NIH] Cell Cycle: The complex series of phenomena, occurring between the end of one cell division and the end of the next, by which cellular material is divided between daughter cells. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell 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] Central Nervous System Diseases: Diseases of any component of the brain (including the cerebral hemispheres, diencephalon, brain stem, and cerebellum) or the spinal cord. [NIH] Central Nervous System Infections: Pathogenic infections of the brain, spinal cord, and meninges. DNA virus infections; RNA virus infections; bacterial infections; mycoplasma infections; Spirochaetales infections; fungal infections; protozoan infections; helminthiasis; and prion diseases may involve the central nervous system as a primary or secondary process. [NIH] 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] Cerebellar: Pertaining to the cerebellum. [EU] Cerebellum: Part of the metencephalon that lies in the posterior cranial fossa behind the brain stem. It is concerned with the coordination of movement. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral Aqueduct: Narrow channel in the mesencephalon that connects the third and
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fourth ventricles. [NIH] Cerebral hemispheres: The two halves of the cerebrum, the part of the brain that controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. The right hemisphere controls muscle movement on the left side of the body, and the left hemisphere controls muscle movement on the right side of the body. [NIH] Cerebral Hemorrhage: Bleeding into a cerebral hemisphere of the brain, including lobar, subcortical white matter, and basal ganglia hemorrhages. Commonly associated conditions include hypertension; intracranial arteriosclerosis; intracranial aneurysm; craniocerebral trauma; intracranial arteriovenous malformations; cerebral amyloid angiopathy; and cerebral infarction. [NIH] 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]
Cerebral Palsy: Refers to a motor disability caused by a brain dysfunction. [NIH] Cerebrospinal: Pertaining to the brain and spinal cord. [EU] Cerebrospinal fluid: CSF. The fluid flowing around the brain and spinal cord. Cerebrospinal fluid is produced in the ventricles in the brain. [NIH] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Cervical: Relating to the neck, or to the neck of any organ or structure. Cervical lymph nodes are located in the neck; cervical cancer refers to cancer of the uterine cervix, which is the lower, narrow end (the "neck") of the uterus. [NIH] Cervix: The lower, narrow end of the uterus that forms a canal between the uterus and vagina. [NIH] Cesarean Section: Extraction of the fetus by means of abdominal hysterotomy. [NIH] Cetirizine: A potent second-generation histamine H1 antagonist that is effective in the treatment of allergic rhinitis, chronic urticaria, and pollen-induced asthma. Unlike many traditional antihistamines, it does not cause drowsiness or anticholinergic side effects. [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] Chelating Agents: Organic chemicals that form two or more coordination bonds with a central metal ion. Heterocyclic rings are formed with the central metal atom as part of the ring. Some biological systems form metal chelates, e.g., the iron-binding porphyrin group of hemoglobin and the magnesium-binding chlorophyll of plants. (From Hawley's Condensed Chemical Dictionary, 12th ed) They are used chemically to remove ions from solutions, medicinally against microorganisms, to treat metal poisoning, and in chemotherapy protocols. [NIH] Chemoreceptor: A receptor adapted for excitation by chemical substances, e.g., olfactory and gustatory receptors, or a sense organ, as the carotid body or the aortic (supracardial) bodies, which is sensitive to chemical changes in the blood stream, especially reduced oxygen content, and reflexly increases both respiration and blood pressure. [EU] Chemotactic Factors: Chemical substances that attract or repel cells or organisms. The concept denotes especially those factors released as a result of tissue injury, invasion, or
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immunologic activity, that attract leukocytes, macrophages, or other cells to the site of infection or insult. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] Chest Pain: Pressure, burning, or numbness in the chest. [NIH] Chest wall: The ribs and muscles, bones, and joints that make up the area of the body between the neck and the abdomen. [NIH] Chiropractic: A system of treating bodily disorders by manipulation of the spine and other parts, based on the belief that the cause is the abnormal functioning of a nerve. [NIH] Chlorophyll: Porphyrin derivatives containing magnesium that act to convert light energy in photosynthetic organisms. [NIH] Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Cholesterol Esters: Fatty acid esters of cholesterol which constitute about two-thirds of the cholesterol in the plasma. The accumulation of cholesterol esters in the arterial intima is a characteristic feature of atherosclerosis. [NIH] Chorea: Involuntary, forcible, rapid, jerky movements that may be subtle or become confluent, markedly altering normal patterns of movement. Hypotonia and pendular reflexes are often associated. Conditions which feature recurrent or persistent episodes of chorea as a primary manifestation of disease are referred to as choreatic disorders. Chorea is also a frequent manifestation of basal ganglia diseases. [NIH] Choreatic Disorders: Acquired and hereditary conditions which feature chorea as a primary manifestation of the disease process. [NIH] Choroid: The thin, highly vascular membrane covering most of the posterior of the eye between the retina and sclera. [NIH] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chromic: Catgut sterilized and impregnated with chromium trioxide. [NIH] Chromium: A trace element that plays a role in glucose metabolism. It has the atomic symbol Cr, atomic number 24, and atomic weight 52. According to the Fourth Annual Report on Carcinogens (NTP85-002,1985), chromium and some of its compounds have been listed as known carcinogens. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic Disease: Disease or ailment of long duration. [NIH] Chronic Fatigue Syndrome: Fatigue caused by the combined effects of different types of prolonged fatigue. [NIH] Chronic Obstructive Pulmonary Disease: Collective term for chronic bronchitis and emphysema. [NIH] Chronic renal: Slow and progressive loss of kidney function over several years, often resulting in end-stage renal disease. People with end-stage renal disease need dialysis or transplantation to replace the work of the kidneys. [NIH] Chronotropic: Affecting the time or rate, as the rate of contraction of the heart. [EU] Chylomicrons: A class of lipoproteins that carry dietary cholesterol and triglycerides from the small intestines to the tissues. [NIH] Ciliary: Inflammation or infection of the glands of the margins of the eyelids. [NIH]
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Ciliary Body: A ring of tissue extending from the scleral spur to the ora serrata of the retina. It consists of the uveal portion and the epithelial portion. The ciliary muscle is in the uveal portion and the ciliary processes are in the epithelial portion. [NIH] Ciliary processes: The extensions or projections of the ciliary body that secrete aqueous humor. [NIH] 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] Cisplatin: An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle. [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] Clindamycin: An antibacterial agent that is a semisynthetic analog of lincomycin. [NIH] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]
Clinical study: A research study in which patients receive treatment in a clinic or other medical facility. Reports of clinical studies can contain results for single patients (case reports) or many patients (case series or clinical trials). [NIH] Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Clone: The term "clone" has acquired a new meaning. It is applied specifically to the bits of inserted foreign DNA in the hybrid molecules of the population. Each inserted segment originally resided in the DNA of a complex genome amid millions of other DNA segment. [NIH]
Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Coagulation: 1. The process of clot formation. 2. In colloid chemistry, the solidification of a sol into a gelatinous mass; an alteration of a disperse phase or of a dissolved solid which causes the separation of the system into a liquid phase and an insoluble mass called the clot or curd. Coagulation is usually irreversible. 3. In surgery, the disruption of tissue by physical means to form an amorphous residuum, as in electrocoagulation and photocoagulation. [EU] Cobalt: A trace element that is a component of vitamin B12. It has the atomic symbol Co, atomic number 27, and atomic weight 58.93. It is used in nuclear weapons, alloys, and pigments. Deficiency in animals leads to anemia; its excess in humans can lead to erythrocytosis. [NIH] Cochlear: Of or pertaining to the cochlea. [EU]
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Cochlear Diseases: Diseases of the cochlea, the part of the inner ear that is concerned with hearing. [NIH] Coenzyme: An organic nonprotein molecule, frequently a phosphorylated derivative of a water-soluble vitamin, that binds with the protein molecule (apoenzyme) to form the active enzyme (holoenzyme). [EU] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Cognition: Intellectual or mental process whereby an organism becomes aware of or obtains knowledge. [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] Collagen disease: A term previously used to describe chronic diseases of the connective tissue (e.g., rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis), but now is thought to be more appropriate for diseases associated with defects in collagen, which is a component of the connective tissue. [NIH] Collapse: 1. A state of extreme prostration and depression, with failure of circulation. 2. Abnormal falling in of the walls of any part of organ. [EU] Colloidal: Of the nature of a colloid. [EU] Colony-Stimulating Factors: Glycoproteins found in a subfraction of normal mammalian plasma and urine. They stimulate the proliferation of bone marrow cells in agar cultures and the formation of colonies of granulocytes and/or macrophages. The factors include interleukin-3 (IL-3), granulocyte colony-stimulating factor (G-CSF), macrophage colonystimulating factor (M-CSF), and granulocyte-macrophage colony-stimulating factor (GMCSF). [NIH] Colorectal: Having to do with the colon or the rectum. [NIH] Combination Therapy: Association of 3 drugs to treat AIDS (AZT + DDC or DDI + protease inhibitor). [NIH] Comorbidity: The presence of co-existing or additional diseases with reference to an initial diagnosis or with reference to the index condition that is the subject of study. Comorbidity may affect the ability of affected individuals to function and also their survival; it may be used as a prognostic indicator for length of hospital stay, cost factors, and outcome or survival. [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and
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C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Compress: A plug used to occludate an orifice in the control of bleeding, or to mop up secretions; an absorbent pad. [NIH] Compulsive Behavior: The behavior of performing an act persistently and repetitively without it leading to reward or pleasure. The act is usually a small, circumscribed behavior, almost ritualistic, yet not pathologically disturbing. Examples of compulsive behavior include twirling of hair, checking something constantly, not wanting pennies in change, straightening tilted pictures, etc. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Computed tomography: CT scan. A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized tomography and computerized axial tomography (CAT) scan. [NIH] Computerized axial tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called CAT scan, computed tomography (CT scan), or computerized tomography. [NIH] Computerized tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized axial tomography (CAT) scan and computed tomography (CT scan). [NIH] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU] Concomitant: Accompanying; accessory; joined with another. [EU] Conduction: The transfer of sound waves, heat, nervous impulses, or electricity. [EU] Cones: One type of specialized light-sensitive cells (photoreceptors) in the retina that provide sharp central vision and color vision. [NIH] Confounding: Extraneous variables resulting in outcome effects that obscure or exaggerate the "true" effect of an intervention. [NIH] Confusion: A mental state characterized by bewilderment, emotional disturbance, lack of
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clear thinking, and perceptual disorientation. [NIH] Congestive heart failure: Weakness of the heart muscle that leads to a buildup of fluid in body tissues. [NIH] 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] Connexin 43: A 43 kD peptide which is a member of the connexin family of gap junction proteins. Connexin 43 is a product of a gene in the alpha class of connexin genes (the alpha-1 gene). It was first isolated from mammalian heart, but is widespread in the body including the brain. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH] Constipation: Infrequent or difficult evacuation of feces. [NIH] Constriction: The act of constricting. [NIH] Constriction, Pathologic: The condition of an anatomical structure's being constricted beyond normal dimensions. [NIH] 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] Contingent Negative Variation: An increasing negative shift of the cortical electrical potentials associated with an anticipated response to an expected stimulus. It is an electrical event indicative of a state of readiness or expectancy. [NIH] Continuum: An area over which the vegetation or animal population is of constantly changing composition so that homogeneous, separate communities cannot be distinguished. [NIH]
Contractility: Capacity for becoming short in response to a suitable stimulus. [EU] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Contralateral: Having to do with the opposite side of the body. [NIH] Control group: In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works. [NIH] Controlled study: An experiment or clinical trial that includes a comparison (control) group. [NIH]
Contusion: A bruise; an injury of a part without a break in the skin. [EU] Conus: A large, circular, white patch around the optic disk due to the exposing of the sclera as a result of degenerative change or congenital abnormality in the choroid and retina. [NIH] Convulsions: A general term referring to sudden and often violent motor activity of cerebral or brainstem origin. Convulsions may also occur in the absence of an electrical cerebral discharge (e.g., in response to hypotension). [NIH] Convulsive: Relating or referring to spasm; affected with spasm; characterized by a spasm or spasms. [NIH] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or
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groups of muscles, in a complex action or series of actions. [NIH] Cor: The muscular organ that maintains the circulation of the blood. c. adiposum a heart that has undergone fatty degeneration or that has an accumulation of fat around it; called also fat or fatty, heart. c. arteriosum the left side of the heart, so called because it contains oxygenated (arterial) blood. c. biloculare a congenital anomaly characterized by failure of formation of the atrial and ventricular septums, the heart having only two chambers, a single atrium and a single ventricle, and a common atrioventricular valve. c. bovinum (L. 'ox heart') a greatly enlarged heart due to a hypertrophied left ventricle; called also c. taurinum and bucardia. c. dextrum (L. 'right heart') the right atrium and ventricle. c. hirsutum, c. villosum. c. mobile (obs.) an abnormally movable heart. c. pendulum a heart so movable that it seems to be hanging by the great blood vessels. c. pseudotriloculare biatriatum a congenital cardiac anomaly in which the heart functions as a three-chambered heart because of tricuspid atresia, the right ventricle being extremely small or rudimentary and the right atrium greatly dilated. Blood passes from the right to the left atrium and thence disease due to pulmonary hypertension secondary to disease of the lung, or its blood vessels, with hypertrophy of the right ventricle. [EU] Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary Arteriosclerosis: Thickening and loss of elasticity of the coronary arteries. [NIH] Coronary Artery Bypass: Surgical therapy of ischemic coronary artery disease achieved by grafting a section of saphenous vein, internal mammary artery, or other substitute between the aorta and the obstructed coronary artery distal to the obstructive lesion. [NIH] Coronary Circulation: The circulation of blood through the coronary vessels of the heart. [NIH]
Coronary Disease: Disorder of cardiac function due to an imbalance between myocardial function and the capacity of the coronary vessels to supply sufficient flow for normal function. It is a form of myocardial ischemia (insufficient blood supply to the heart muscle) caused by a decreased capacity of the coronary vessels. [NIH] Coronary heart disease: A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Coronary Vessels: The veins and arteries of the heart. [NIH] Corpus: The body of the uterus. [NIH] Corpus Luteum: The yellow glandular mass formed in the ovary by an ovarian follicle that has ruptured and discharged its ovum. [NIH] Corrosion: Irreversible destruction of skin tissue. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Corticosteroid: Any of the steroids elaborated by the adrenal cortex (excluding the sex
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hormones of adrenal origin) in response to the release of corticotrophin (adrenocorticotropic hormone) by the pituitary gland, to any of the synthetic equivalents of these steroids, or to angiotensin II. They are divided, according to their predominant biological activity, into three major groups: glucocorticoids, chiefly influencing carbohydrate, fat, and protein metabolism; mineralocorticoids, affecting the regulation of electrolyte and water balance; and C19 androgens. Some corticosteroids exhibit both types of activity in varying degrees, and others exert only one type of effect. The corticosteroids are used clinically for hormonal replacement therapy, for suppression of ACTH secretion by the anterior pituitary, as antineoplastic, antiallergic, and anti-inflammatory agents, and to suppress the immune response. Called also adrenocortical hormone and corticoid. [EU] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to stress. [NIH] Cortisone: A natural steroid hormone produced in the adrenal gland. It can also be made in the laboratory. Cortisone reduces swelling and can suppress immune responses. [NIH] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Craniocerebral Trauma: Traumatic injuries involving the cranium and intracranial structures (i.e., brain; cranial nerves; meninges; and other structures). Injuries may be classified by whether or not the skull is penetrated (i.e., penetrating vs. nonpenetrating) or whether there is an associated hemorrhage. [NIH] Criterion: A standard by which something may be judged. [EU] Critical Care: Health care provided to a critically ill patient during a medical emergency or crisis. [NIH] Critical Illness: A disease or state in which death is possible or imminent. [NIH] Crystallization: The formation of crystals; conversion to a crystalline form. [EU] CSF: Cerebrospinal fluid. The fluid flowing around the brain and spinal cord. CSF is produced in the ventricles of the brain. [NIH] Cues: Signals for an action; that specific portion of a perceptual field or pattern of stimuli to which a subject has learned to respond. [NIH] Cumulative Trauma Disorders: Harmful and painful condition caused by overuse or overexertion of some part of the musculoskeletal system, often resulting from work-related physical activities. It is characterized by inflammation, pain, or dysfunction of the involved joints, bones, ligaments, and nerves. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Having to do with the skin. [NIH] Cyanide: An extremely toxic class of compounds that can be lethal on inhaling of ingesting in minute quantities. [NIH] Cyanosis: A bluish or purplish discoloration of the skin and mucous membranes due to an increase in the amount of deoxygenated hemoglobin in the blood or a structural defect in the hemoglobin molecule. [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] Cyclooxygenase Inhibitors: Compounds or agents that combine with cyclooxygenase (prostaglandin-endoperoxide synthase) and thereby prevent its substrate-enzyme combination with arachidonic acid and the formation of eicosanoids, prostaglandins, and thromboxanes. [NIH]
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Cystathionine beta-Synthase: A multifunctional pyridoxal phosphate enzyme. In the second stage of cysteine biosynthesis it catalyzes the reaction of homocysteine with serine to form cystathionine with the elimination of water. Deficiency of this enzyme leads to hyperhomocysteinemia and homocystinuria. EC 4.2.1.22. [NIH] Cysteine: A thiol-containing non-essential amino acid that is oxidized to form cystine. [NIH] Cystine: A covalently linked dimeric nonessential amino acid formed by the oxidation of cysteine. Two molecules of cysteine are joined together by a disulfide bridge to form cystine. [NIH]
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] Cytochrome b: Cytochromes (electron-transporting proteins) with protoheme or a related heme as the prosthetic group. The prosthetic group is not covalently bound to the protein moiety. [NIH] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytomegalovirus: A genus of the family Herpesviridae, subfamily Betaherpesvirinae, infecting the salivary glands, liver, spleen, lungs, eyes, and other organs, in which they produce characteristically enlarged cells with intranuclear inclusions. Infection with Cytomegalovirus is also seen as an opportunistic infection in AIDS. [NIH] Cytopenia: A reduction in the number of blood cells. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. [NIH] Cytostatic: An agent that suppresses cell growth and multiplication. [EU] Cytotoxic: Cell-killing. [NIH] Cytotoxicity: Quality of being capable of producing a specific toxic action upon cells of special organs. [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]
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De novo: In cancer, the first occurrence of cancer in the body. [NIH] Decarboxylation: The removal of a carboxyl group, usually in the form of carbon dioxide, from a chemical compound. [NIH] Decidua: The epithelial lining of the endometrium that is formed before the fertilized ovum reaches the uterus. The fertilized ovum embeds in the decidua. If the ovum is not fertilized, the decidua is shed during menstruation. [NIH] Decompensation: Failure of compensation; cardiac decompensation is marked by dyspnea, venous engorgement, and edema. [EU] Decongestant: An agent that reduces congestion or swelling. [EU] Defense Mechanisms: Unconscious process used by an individual or a group of individuals in order to cope with impulses, feelings or ideas which are not acceptable at their conscious level; various types include reaction formation, projection and self reversal. [NIH] Deferoxamine: Natural product isolated from Streptomyces pilosus. It forms iron complexes and is used as a chelating agent, particularly in the form of its mesylate. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Dehydration: The condition that results from excessive loss of body water. [NIH] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Delirium: (DSM III-R) an acute, reversible organic mental disorder characterized by reduced ability to maintain attention to external stimuli and disorganized thinking as manifested by 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] Denaturation: Rupture of the hydrogen bonds by heating a DNA solution and then cooling it rapidly causes the two complementary strands to separate. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Dendritic: 1. Branched like a tree. 2. Pertaining to or possessing dendrites. [EU] 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
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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]
Depersonalization: Alteration in the perception of the self so that the usual sense of one's own reality is lost, manifested in a sense of unreality or self-estrangement, in changes of body image, or in a feeling that one does not control his own actions and speech; seen in depersonalization disorder, schizophrenic disorders, and schizotypal personality disorder. Some do not draw a distinction between depersonalization and derealization, using depersonalization to include both. [EU] 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] Derealization: Is characterized by the loss of the sense of reality concerning one's surroundings. [NIH] Dermatitis: Any inflammation of the skin. [NIH] Detoxification: Treatment designed to free an addict from his drug habit. [EU] 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] Dexamethasone: (11 beta,16 alpha)-9-Fluoro-11,17,21-trihydroxy-16-methylpregna-1,4diene-3,20-dione. An anti-inflammatory glucocorticoid used either in the free alcohol or esterified form in treatment of conditions that respond generally to cortisone. [NIH] 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 Ketoacidosis: Complication of diabetes resulting from severe insulin deficiency coupled with an absolute or relative increase in glucagon concentration. The metabolic acidosis is caused by the breakdown of adipose stores and resulting increased levels of free fatty acids. Glucagon accelerates the oxidation of the free fatty acids producing excess ketone bodies (ketosis). [NIH] Diabetic Retinopathy: Retinopathy associated with diabetes mellitus, which may be of the background type, progressively characterized by microaneurysms, interretinal punctuate macular edema, or of the proliferative type, characterized by neovascularization of the retina and optic disk, which may project into the vitreous, proliferation of fibrous tissue, vitreous hemorrhage, and retinal detachment. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH]
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Dialysate: A cleansing liquid used in the two major forms of dialysis--hemodialysis and peritoneal dialysis. [NIH] Dialyzer: A part of the hemodialysis machine. (See hemodialysis under dialysis.) The dialyzer has two sections separated by a membrane. One section holds dialysate. The other holds the patient's blood. [NIH] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Diarrhoea: Abnormal frequency and liquidity of faecal discharges. [EU] Diastole: Period of relaxation of the heart, especially the ventricles. [NIH] Diastolic: Of or pertaining to the diastole. [EU] Diastolic pressure: The lowest pressure to which blood pressure falls between contractions of the ventricles. [NIH] Diencephalon: The paired caudal parts of the prosencephalon from which the thalamus, hypothalamus, epithalamus, and subthalamus are derived. [NIH] Diffusion: The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space; a major mechanism of biological transport. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive system: The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] Digestive tract: The organs through which food passes when food is eaten. These organs are the mouth, esophagus, stomach, small and large intestines, and rectum. [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] Dilution: A diluted or attenuated medicine; in homeopathy, the diffusion of a given quantity of a medicinal agent in ten or one hundred times the same quantity of water. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Disease Susceptibility: A constitution or condition of the body which makes the tissues react in special ways to certain extrinsic stimuli and thus tends to make the individual more than usually susceptible to certain diseases. [NIH] Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [EU] Diskectomy: Excision, in part or whole, of an intervertebral disk. The most common indication is disk displacement or herniation. In addition to standard surgical removal, it
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can be performed by percutaneous diskectomy or by laparoscopic diskectomy, the former being the more common. [NIH] Disorientation: The loss of proper bearings, or a state of mental confusion as to time, place, or identity. [EU] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Dissociative Disorders: Sudden temporary alterations in the normally integrative functions of consciousness. [NIH] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Disulphide: A covalent bridge formed by the oxidation of two cysteine residues to a cystine residue. The-S-S-bond is very strong and its presence confers additional stability. [NIH] Diuresis: Increased excretion of urine. [EU] Diuretic: A drug that increases the production of urine. [NIH] Dizziness: An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. [NIH] Domesticated: Species in which the evolutionary process has been influenced by humans to meet their needs. [NIH] Dominance: In genetics, the full phenotypic expression of a gene in both heterozygotes and homozygotes. [EU] Dopa: The racemic or DL form of DOPA, an amino acid found in various legumes. The dextro form has little physiologic activity but the levo form (levodopa) is a very important physiologic mediator and precursor and pharmacological agent. [NIH] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] Dorsal: 1. Pertaining to the back or to any dorsum. 2. Denoting a position more toward the back surface than some other object of reference; same as posterior in human anatomy; superior in the anatomy of quadrupeds. [EU] Dorsum: A plate of bone which forms the posterior boundary of the sella turcica. [NIH] Dose-dependent: Refers to the effects of treatment with a drug. If the effects change when the dose of the drug is changed, the effects are said to be dose dependent. [NIH] Dose-limiting: Describes side effects of a drug or other treatment that are serious enough to prevent an increase in dose or level of that treatment. [NIH] Doxazosin: A selective alpha-1-adrenergic blocker that lowers serum cholesterol. It is also
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effective in the treatment of hypertension. [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 Design: The molecular designing of drugs for specific purposes (such as DNAbinding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include pharmacokinetics, dosage analysis, or drug administration analysis. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] Duct: A tube through which body fluids pass. [NIH] Duodenum: The first part of the small intestine. [NIH] Dura mater: The outermost, toughest, and most fibrous of the three membranes (meninges) covering the brain and spinal cord; called also pachymeninx. [EU] Dyes: Chemical substances that are used to stain and color other materials. The coloring may or may not be permanent. Dyes can also be used as therapeutic agents and test reagents in medicine and scientific research. [NIH] Dynorphins: A class of opioid peptides including dynorphin A, dynorphin B, and smaller fragments of these peptides. Dynorphins prefer kappa-opioid receptors (receptors, opioid, kappa) and have been shown to play a role as central nervous system transmitters. [NIH] Dyskinesia: Impairment of the power of voluntary movement, resulting in fragmentary or incomplete movements. [EU] Dyslipidemia: Disorders in the lipoprotein metabolism; classified as hypercholesterolemia, hypertriglyceridemia, combined hyperlipidemia, and low levels of high-density lipoprotein (HDL) cholesterol. All of the dyslipidemias can be primary or secondary. Both elevated levels of low-density lipoprotein (LDL) cholesterol and low levels of HDL cholesterol predispose to premature atherosclerosis. [NIH] Dyspepsia: Impaired digestion, especially after eating. [NIH] Dysphoria: Disquiet; restlessness; malaise. [EU] Dysphoric: A feeling of unpleasantness and discomfort. [NIH] Dysplasia: Cells that look abnormal under a microscope but are not cancer. [NIH] Dyspnea: Difficult or labored breathing. [NIH] Dyspnoea: Difficult or laboured breathing. [EU] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] Eating Disorders: A group of disorders characterized by physiological and psychological disturbances in appetite or food intake. [NIH] Eclampsia: Onset of convulsions or coma in a previously diagnosed pre-eclamptic patient.
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[NIH]
Eczema: A pruritic papulovesicular dermatitis occurring as a reaction to many endogenous and exogenous agents (Dorland, 27th ed). [NIH] Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] 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] Ehrlichiosis: A tick-borne disease characterized by fever, headache, myalgias, anorexia, and occasionally rash. In humans the disease is caused by Ehrlichia chaffeensis, in dogs it is caused by E. canis, and in horses, E. equi. [NIH] Eicosanoids: A class of oxygenated, endogenous, unsaturated fatty acids derived from arachidonic acid. They include prostaglandins, leukotrienes, thromboxanes, and hydroxyeicosatetraenoic acid compounds (HETE). They are hormone-like substances that act near the site of synthesis without altering functions throughout the body. [NIH] Elasticity: Resistance and recovery from distortion of shape. [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] Electric shock: A dangerous patho-physiological effect resulting from an electric current passing through the body of a human or animal. [NIH] Electrochemistry: The study of chemical changes resulting from electrical action and electrical activity resulting from chemical changes. [NIH] Electrocoagulation: Electrosurgical procedures used to treat hemorrhage (e.g., bleeding ulcers) and to ablate tumors, mucosal lesions, and refractory arrhythmias. [NIH] Electrode: Component of the pacing system which is at the distal end of the lead. It is the interface with living cardiac tissue across which the stimulus is transmitted. [NIH] Electrolysis: Destruction by passage of a galvanic electric current, as in disintegration of a chemical compound in solution. [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] Electronystagmography: Recording of nystagmus based on changes in the electrical field surrounding the eye produced by the difference in potential between the cornea and the retina. [NIH] Electrophoresis: An electrochemical process in which macromolecules or colloidal particles with a net electric charge migrate in a solution under the influence of an electric current. [NIH]
Electrophysiological: Pertaining to electrophysiology, that is a branch of physiology that is
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concerned with the electric phenomena associated with living bodies and involved in their functional activity. [EU] Electroplating: Coating with a metal or alloy by electrolysis. [NIH] Emboli: Bit of foreign matter which enters the blood stream at one point and is carried until it is lodged or impacted in an artery and obstructs it. It may be a blood clot, an air bubble, fat or other tissue, or clumps of bacteria. [NIH] Embolism: Blocking of a blood vessel by a blood clot or foreign matter that has been transported from a distant site by the blood stream. [NIH] Embolization: The blocking of an artery by a clot or foreign material. Embolization can be done as treatment to block the flow of blood to a tumor. [NIH] Embolus: Bit of foreign matter which enters the blood stream at one point and is carried until it is lodged or impacted in an artery and obstructs it. It may be a blood clot, an air bubble, fat or other tissue, or clumps of bacteria. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Embryo Transfer: Removal of a mammalian embryo from one environment and replacement in the same or a new environment. The embryo is usually in the pre-nidation phase, i.e., a blastocyst. The process includes embryo or blastocyst transplantation or transfer after in vitro fertilization and transfer of the inner cell mass of the blastocyst. It is not used for transfer of differentiated embryonic tissue, e.g., germ layer cells. [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] Emulsion: A preparation of one liquid distributed in small globules throughout the body of a second liquid. The dispersed liquid is the discontinuous phase, and the dispersion medium is the continuous phase. When oil is the dispersed liquid and an aqueous solution is the continuous phase, it is known as an oil-in-water emulsion, whereas when water or aqueous solution is the dispersed phase and oil or oleaginous substance is the continuous phase, it is known as a water-in-oil emulsion. Pharmaceutical emulsions for which official standards have been promulgated include cod liver oil emulsion, cod liver oil emulsion with malt, liquid petrolatum emulsion, and phenolphthalein in liquid petrolatum emulsion. [EU] Encephalitis: Inflammation of the brain due to infection, autoimmune processes, toxins, and other conditions. Viral infections (see encephalitis, viral) are a relatively frequent cause of this condition. [NIH] Encephalitis, Viral: Inflammation of brain parenchymal tissue as a result of viral infection. Encephalitis may occur as primary or secondary manifestation of Togaviridae infections; Herpesviridae infections; Adenoviridae infections; Flaviviridae infections; Bunyaviridae infections; Picornaviridae infections; Paramyxoviridae infections; Orthomyxoviridae infections; Retroviridae infections; and Arenaviridae infections. [NIH] Encephalopathy: A disorder of the brain that can be caused by disease, injury, drugs, or chemicals. [NIH] Endarterectomy: Surgical excision, performed under general anesthesia, of the atheromatous tunica intima of an artery. When reconstruction of an artery is performed as an endovascular procedure through a catheter, it is called atherectomy. [NIH] Endemic: Present or usually prevalent in a population or geographical area at all times; said of a disease or agent. Called also endemial. [EU]
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Endocarditis: Exudative and proliferative inflammatory alterations of the endocardium, characterized by the presence of vegetations on the surface of the endocardium or in the endocardium itself, and most commonly involving a heart valve, but sometimes affecting the inner lining of the cardiac chambers or the endocardium elsewhere. It may occur as a primary disorder or as a complication of or in association with another disease. [EU] Endocardium: The innermost layer of the heart, comprised of endothelial cells. [NIH] Endocrine Glands: Ductless glands that secrete substances which are released directly into the circulation and which influence metabolism and other body functions. [NIH] Endocrine System: The system of glands that release their secretions (hormones) directly into the circulatory system. In addition to the endocrine glands, included are the chromaffin system and the neurosecretory systems. [NIH] Endocrinology: A subspecialty of internal medicine concerned with the metabolism, physiology, and disorders of the endocrine system. [NIH] Endonucleases: Enzymes that catalyze the hydrolysis of the internal bonds and thereby the formation of polynucleotides or oligonucleotides from ribo- or deoxyribonucleotide chains. EC 3.1.-. [NIH] Endorphins: One of the three major groups of endogenous opioid peptides. They are large peptides derived from the pro-opiomelanocortin precursor. The known members of this group are alpha-, beta-, and gamma-endorphin. The term endorphin is also sometimes used to refer to all opioid peptides, but the narrower sense is used here; opioid peptides is used for the broader group. [NIH] Endoscope: A thin, lighted tube used to look at tissues inside the body. [NIH] Endoscopic: A technique where a lateral-view endoscope is passed orally to the duodenum for visualization of the ampulla of Vater. [NIH] Endoscopy: Endoscopic examination, therapy or surgery performed on interior parts of the body. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium, 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] Endotoxemia: A condition characterized by the presence of endotoxins in the blood. If endotoxemia is the result of gram-negative rod-shaped bacteria, shock may occur. [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]
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End-stage renal: Total chronic kidney failure. When the kidneys fail, the body retains fluid and harmful wastes build up. A person with ESRD needs treatment to replace the work of the failed kidneys. [NIH] Energetic: Exhibiting energy : strenuous; operating with force, vigour, or effect. [EU] Energy balance: Energy is the capacity of a body or a physical system for doing work. Energy balance is the state in which the total energy intake equals total energy needs. [NIH] Energy Intake: Total number of calories taken in daily whether ingested or by parenteral routes. [NIH] Enhancer: Transcriptional element in the virus genome. [NIH] Enkephalins: One of the three major families of endogenous opioid peptides. The enkephalins are pentapeptides that are widespread in the central and peripheral nervous systems and in the adrenal medulla. [NIH] Enterocolitis: Inflammation of the intestinal mucosa of the small and large bowel. [NIH] Enterotoxins: Substances that are toxic to the intestinal tract causing vomiting, diarrhea, etc.; most common enterotoxins are produced by bacteria. [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] Eosinophilia: Abnormal increase in eosinophils in the blood, tissues or organs. [NIH] Eosinophilic: A condition found primarily in grinding workers caused by a reaction of the pulmonary tissue, in particular the eosinophilic cells, to dust that has entered the lung. [NIH] Eosinophilic Gastroenteritis: Infection and swelling of the lining of the stomach, small intestine, or large intestine. The infection is caused by white blood cells (eosinophils). [NIH] Eosinophils: Granular leukocytes with a nucleus that usually has two lobes connected by a slender thread of chromatin, and cytoplasm containing coarse, round granules that are uniform in size and stainable by eosin. [NIH] Ephedrine: An alpha- and beta-adrenergic agonist that may also enhance release of norepinephrine. It has been used in the treatment of several disorders including asthma, heart failure, rhinitis, and urinary incontinence, and for its central nervous system stimulatory effects in the treatment of narcolepsy and depression. It has become less extensively used with the advent of more selective agonists. [NIH] Epidemic: Occurring suddenly in numbers clearly in excess of normal expectancy; said especially of infectious diseases but applied also to any disease, injury, or other healthrelated event occurring in such outbreaks. [EU] Epidemiological: Relating to, or involving epidemiology. [EU] Epidermal: Pertaining to or resembling epidermis. Called also epidermic or epidermoid. [EU] 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
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epidermidis); 3) granular layer (stratum granulosum epidermidis); 4) clear layer (stratum lucidum epidermidis); and 5) horny layer (stratum corneum epidermidis). [NIH] Epidural: The space between the wall of the spinal canal and the covering of the spinal cord. An epidural injection is given into this space. [NIH] Epidural Space: Space between the dura mater and the walls of the vertebral canal. [NIH] Epigastric: Having to do with the upper middle area of the abdomen. [NIH] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Epitopes: Sites on an antigen that interact with specific antibodies. [NIH] Equipment and Supplies: Expendable and nonexpendable equipment, supplies, apparatus, and instruments that are used in diagnostic, surgical, therapeutic, scientific, and experimental procedures. [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] Erythema: Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of causes. [NIH] Erythrocyte Volume: Volume of circulating erythrocytes. It is usually measured by radioisotope dilution technique. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Erythropoietin: Glycoprotein hormone, secreted chiefly by the kidney in the adult and the liver in the fetus, that acts on erythroid stem cells of the bone marrow to stimulate proliferation and differentiation. [NIH] Esophagitis: Inflammation, acute or chronic, of the esophagus caused by bacteria, chemicals, or trauma. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]
Essential Tremor: A rhythmic, involuntary, purposeless, oscillating movement resulting from the alternate contraction and relaxation of opposing groups of muscles. [NIH] Estradiol: The most potent mammalian estrogenic hormone. It is produced in the ovary, placenta, testis, and possibly the adrenal cortex. [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]
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Ethanolamine: A viscous, hygroscopic amino alcohol with an ammoniacal odor. It is widely distributed in biological tissue and is a component of lecithin. It is used as a surfactant, fluorimetric reagent, and to remove CO2 and H2S from natural gas and other gases. [NIH] Ether: One of a class of organic compounds in which any two organic radicals are attached directly to a single oxygen atom. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Evacuation: An emptying, as of the bowels. [EU] Evoke: The electric response recorded from the cerebral cortex after stimulation of a peripheral sense organ. [NIH] Evoked Potentials: The electric response evoked in the central nervous system by stimulation of sensory receptors or some point on the sensory pathway leading from the receptor to the cortex. The evoked stimulus can be auditory, somatosensory, or visual, although other modalities have been reported. Event-related potentials is sometimes used synonymously with evoked potentials but is often associated with the execution of a motor, cognitive, or psychophysiological task, as well as with the response to a stimulus. [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] 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] Exons: Coding regions of messenger RNA included in the genetic transcript which survive the processing of RNA in cell nuclei to become part of a spliced messenger of structural RNA in the cytoplasm. They include joining and diversity exons of immunoglobulin genes. [NIH]
Exotoxin: Toxic substance excreted by living bacterial cells. [NIH] Expander: Any of several colloidal substances of high molecular weight. used as a blood or plasma substitute in transfusion for increasing the volume of the circulating blood. called also extender. [NIH] Expiration: The act of breathing out, or expelling air from the lungs. [EU] Extender: Any of several colloidal substances of high molecular weight, used as a blood or plasma substitute in transfusion for increasing the volume of the circulating blood. [NIH] Extensor: A muscle whose contraction tends to straighten a limb; the antagonist of a flexor. [NIH]
External-beam radiation: Radiation therapy that uses a machine to aim high-energy rays at
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the cancer. Also called external radiation. [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 Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] Extracorporeal: Situated or occurring outside the body. [EU] Extracorporeal Circulation: Diversion of blood flow through a circuit located outside the body but continuous with the bodily circulation. [NIH] Extraction: The process or act of pulling or drawing out. [EU] Extrapyramidal: Outside of the pyramidal tracts. [EU] Extravascular: Situated or occurring outside a vessel or the vessels. [EU] Extremity: A limb; an arm or leg (membrum); sometimes applied specifically to a hand or foot. [EU] Facial: Of or pertaining to the face. [EU] Facial Pain: Pain in the facial region including orofacial pain and craniofacial pain. Associated conditions include local inflammatory and neoplastic disorders and neuralgic syndromes involving the trigeminal, facial, and glossopharyngeal nerves. Conditions which feature recurrent or persistent facial pain as the primary manifestation of disease are referred to as facial pain syndromes. [NIH] Facial Paralysis: Severe or complete loss of facial muscle motor function. This condition may result from central or peripheral lesions. Damage to CNS motor pathways from the cerebral cortex to the facial nuclei in the pons leads to facial weakness that generally spares the forehead muscles. Facial nerve diseases generally results in generalized hemifacial weakness. Neuromuscular junction diseases and muscular diseases may also cause facial paralysis or paresis. [NIH] Faecal: Pertaining to or of the nature of feces. [EU] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fasciitis: Inflammation of the fascia. There are three major types: 1) Eosinophilic fasciitis, an inflammatory reaction with eosinophilia, producing hard thickened skin with an orangepeel configuration suggestive of scleroderma and considered by some a variant of scleroderma; 2) Necrotizing fasciitis, a serious fulminating infection (usually by a beta hemolytic Streptococcus) causing extensive necrosis of superficial fascia; 3) Nodular/Pseudosarcomatous/Proliferative fasciitis, characterized by a rapid growth of fibroblasts with mononuclear inflammatory cells and proliferating capillaries in soft tissue, often the forearm; it is not malignant but is sometimes mistaken for fibrosarcoma. [NIH] Fat: Total lipids including phospholipids. [NIH] Fatal Outcome: Death resulting from the presence of a disease in an individual, as shown by a single case report or a limited number of patients. This should be differentiated from death, the physiological cessation of life and from mortality, an epidemiological or statistical concept. [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.
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[NIH]
Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH] Febrile: Pertaining to or characterized by fever. [EU] Feces: The excrement discharged from the intestines, consisting of bacteria, cells exfoliated from the intestines, secretions, chiefly of the liver, and a small amount of food residue. [EU] Femoral: Pertaining to the femur, or to the thigh. [EU] Femoral Artery: The main artery of the thigh, a continuation of the external iliac artery. [NIH] Fenoldopam: A dopamine D1 receptor agonist that is used as an antihypertensive agent. It lowers blood pressure through arteriolar vasodilation. [NIH] Fertilization in Vitro: Fertilization of an egg outside the body when the egg is normally fertilized in the body. [NIH] Fertilizers: Substances or mixtures that are added to the soil to supply nutrients or to make available nutrients already present in the soil, in order to increase plant growth and productivity. [NIH] Fetal Blood: Blood of the fetus. Exchange of nutrients and waste between the fetal and maternal blood occurs via the placenta. The cord blood is blood contained in the umbilical vessels at the time of delivery. [NIH] Fetal Distress: Adverse or threatening condition of the fetus identified by fetal bradycardia or tachycardia and passage of meconium in vertex presentation. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibrillation: A small, local, involuntary contraction of muscle, invisible under the skin, resulting from spontaneous activation of single muscle cells or muscle fibres. [EU] Fibrin: A protein derived from fibrinogen in the presence of thrombin, which forms part of the blood clot. [NIH] Fibrinogen: Plasma glycoprotein clotted by thrombin, composed of a dimer of three nonidentical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products. [NIH] Fibrinolysis: The natural enzymatic dissolution of fibrin. [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibrosarcoma: A type of soft tissue sarcoma that begins in fibrous tissue, which holds bones, muscles, and other organs in place. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Fibula: The bone of the lower leg lateral to and smaller than the tibia. In proportion to its length, it is the most slender of the long bones. [NIH] Filtration: The passage of a liquid through a filter, accomplished by gravity, pressure, or vacuum (suction). [EU] Fistula: Abnormal communication most commonly seen between two internal organs, or between an internal organ and the surface of the body. [NIH] Flatus: Gas passed through the rectum. [NIH]
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Fludrocortisone: A synthetic mineralocorticoid with anti-inflammatory activity. [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] Fluorophotometry: Measurement of light given off by fluorescein in order to assess the integrity of various ocular barriers. The method is used to investigate the blood-aqueous barrier, blood-retinal barrier, aqueous flow measurements, corneal endothelial permeability, and tear flow dynamics. [NIH] Flushing: A transient reddening of the face that may be due to fever, certain drugs, exertion, stress, or a disease process. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Food Hypersensitivity: Gastrointestinal disturbances, skin eruptions, or shock due to allergic reactions to allergens ingested in food. [NIH] Foot Care: Taking special steps to avoid foot problems such as sores, cuts, bunions, and calluses. Good care includes daily examination of the feet, toes, and toenails and choosing shoes and socks or stockings that fit well. People with diabetes have to take special care of their feet because nerve damage and reduced blood flow sometimes mean they will have less feeling in their feet than normal. They may not notice cuts and other problems as soon as they should. [NIH] Foot Ulcer: Lesion on the surface of the skin of the foot, usually accompanied by inflammation. The lesion may become infected or necrotic and is frequently associated with diabetes or leprosy. [NIH] Foramen: A natural hole of perforation, especially one in a bone. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Fossa: A cavity, depression, or pit. [NIH] Fourth Ventricle: An irregularly shaped cavity in the rhombencephalon, between the medulla oblongata, the pons, and the isthmus in front, and the cerebellum behind. It is continuous with the central canal of the cord below and with the cerebral aqueduct above, and through its lateral and median apertures it communicates with the subarachnoid space. [NIH]
Frostbite: Damage to tissues as the result of low environmental temperatures. [NIH] Fungi: A kingdom of eukaryotic, heterotrophic organisms that live as saprobes or parasites, including mushrooms, yeasts, smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi refer to those that grow as multicelluar colonies (mushrooms and molds). [NIH] Gadolinium: An element of the rare earth family of metals. It has the atomic symbol Gd, atomic number 64, and atomic weight 157.25. Its oxide is used in the control rods of some nuclear reactors. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gamma Rays: Very powerful and penetrating, high-energy electromagnetic radiation of shorter wavelength than that of x-rays. They are emitted by a decaying nucleus, usually between 0.01 and 10 MeV. They are also called nuclear x-rays. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Ganglion: 1. A knot, or knotlike mass. 2. A general term for a group of nerve cell bodies located outside the central nervous system; occasionally applied to certain nuclear groups
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within the brain or spinal cord, e.g. basal ganglia. 3. A benign cystic tumour occurring on a aponeurosis or tendon, as in the wrist or dorsum of the foot; it consists of a thin fibrous capsule enclosing a clear mucinous fluid. [EU] Gangrene: Death and putrefaction of tissue usually due to a loss of blood supply. [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 Emptying: The evacuation of food from the stomach into the duodenum. [NIH] Gastric Juices: Liquids produced in the stomach to help break down food and kill bacteria. [NIH]
Gastric Mucosa: Surface epithelium in the stomach that invaginates into the lamina propria, forming gastric pits. Tubular glands, characteristic of each region of the stomach (cardiac, gastric, and pyloric), empty into the gastric pits. The gastric mucosa is made up of several different kinds of cells. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]
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] Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gastroparesis: Nerve or muscle damage in the stomach. Causes slow digestion and emptying, vomiting, nausea, or bloating. Also called delayed gastric emptying. [NIH] Gelatin: A product formed from skin, white connective tissue, or bone collagen. It is used as a protein food adjuvant, plasma substitute, hemostatic, suspending agent in pharmaceutical preparations, and in the manufacturing of capsules and suppositories. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]
Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [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 testing: Analyzing DNA to look for a genetic alteration that may indicate an increased risk for developing a specific disease or disorder. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genital: Pertaining to the genitalia. [EU]
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Genitourinary: Pertaining to the genital and urinary organs; urogenital; urinosexual. [EU] Genomics: The systematic study of the complete DNA sequences (genome) of organisms. [NIH]
Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Geriatric: Pertaining to the treatment of the aged. [EU] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] Gestational: Psychosis attributable to or occurring during pregnancy. [NIH] Gestational Age: Age of the conceptus. In humans, this may be assessed by medical history, physical examination, early immunologic pregnancy tests, radiography, ultrasonography, and amniotic fluid analysis. [NIH] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus. [EU]
Glomerular Filtration Rate: The volume of water filtered out of plasma through glomerular capillary walls into Bowman's capsules per unit of time. It is considered to be equivalent to inulin clearance. [NIH] Glomeruli: Plural of glomerulus. [NIH] Glomerulonephritis: Glomerular disease characterized by an inflammatory reaction, with leukocyte infiltration and cellular proliferation of the glomeruli, or that appears to be the result of immune glomerular injury. [NIH] Glomerulus: A tiny set of looping blood vessels in the nephron where blood is filtered in the kidney. [NIH] Glossopharyngeal Nerve: The 9th cranial nerve. The glossopharyngeal nerve is a mixed motor and sensory nerve; it conveys somatic and autonomic efferents as well as general, special, and visceral afferents. Among the connections are motor fibers to the stylopharyngeus muscle, parasympathetic fibers to the parotid glands, general and taste afferents from the posterior third of the tongue, the nasopharynx, and the palate, and afferents from baroreceptors and chemoreceptors of the carotid sinus. [NIH] Glottis: The vocal apparatus of the larynx, consisting of the true vocal cords (plica vocalis) and the opening between them (rima glottidis). [NIH] Glucocorticoid: A compound that belongs to the family of compounds called corticosteroids (steroids). Glucocorticoids affect metabolism and have anti-inflammatory and immunosuppressive effects. They may be naturally produced (hormones) or synthetic (drugs). [NIH] Gluconeogenesis: The process by which glucose is formed from a non-carbohydrate source. [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]
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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] Glutamate: Excitatory neurotransmitter of the brain. [NIH] Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. [NIH] Glycogen: A sugar stored in the liver and muscles. It releases glucose into the blood when cells need it for energy. Glycogen is the chief source of stored fuel in the body. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Gonadal: Pertaining to a gonad. [EU] Goniotomy: A surgical procedure for congenital glaucoma in which a sweeping incision is made in the neshwork at the filtration angle by means of a knife-needle inserted through the opposite limbus and carried across the anterior chamber parallel to the iris. [NIH] Gout: Hereditary metabolic disorder characterized by recurrent acute arthritis, hyperuricemia and deposition of sodium urate in and around the joints, sometimes with formation of uric acid calculi. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Gp120: 120-kD HIV envelope glycoprotein which is involved in the binding of the virus to its membrane receptor, the CD4 molecule, found on the surface of certain cells in the body. [NIH]
Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Grafting: The operation of transfer of tissue from one site to another. [NIH] Gram-negative: Losing the stain or decolorized by alcohol in Gram's method of staining, a primary characteristic of bacteria having a cell wall composed of a thin layer of peptidoglycan covered by an outer membrane of lipoprotein and lipopolysaccharide. [EU] Gram-Negative Bacteria: Bacteria which lose crystal violet stain but are stained pink when treated by Gram's method. [NIH] Gram-positive: Retaining the stain or resisting decolorization by alcohol in Gram's method of staining, a primary characteristic of bacteria whose cell wall is composed of a thick layer of peptidologlycan with attached teichoic acids. [EU] Gram-Positive Bacteria: Bacteria which retain the crystal violet stain when treated by Gram's method. [NIH] Granulocyte Colony-Stimulating Factor: A glycoprotein of MW 25 kDa containing internal disulfide bonds. It induces the survival, proliferation, and differentiation of neutrophilic granulocyte precursor cells and functionally activates mature blood neutrophils. Among the family of colony-stimulating factors, G-CSF is the most potent inducer of terminal differentiation to granulocytes and macrophages of leukemic myeloid cell lines. [NIH] Granulocyte-Macrophage Colony-Stimulating Factor: An acidic glycoprotein of MW 23 kDa with internal disulfide bonds. The protein is produced in response to a number of inflammatory mediators by mesenchymal cells present in the hemopoietic environment and at peripheral sites of inflammation. GM-CSF is able to stimulate the production of
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neutrophilic granulocytes, macrophages, and mixed granulocyte-macrophage colonies from bone marrow cells and can stimulate the formation of eosinophil colonies from fetal liver progenitor cells. GM-CSF can also stimulate some functional activities in mature granulocytes and macrophages. [NIH] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Granulocytopenia: A deficiency in the number of granulocytes, a type of white blood cell. [NIH]
Granuloma: A relatively small nodular inflammatory lesion containing grouped mononuclear phagocytes, caused by infectious and noninfectious agents. [NIH] Granulomatous Disease, Chronic: A recessive X-linked defect of leukocyte function in which phagocytic cells ingest but fail to digest bacteria, resulting in recurring bacterial infections with granuloma formation. [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] Guanethidine: An antihypertensive agent that acts by inhibiting selectively transmission in post-ganglionic adrenergic nerves. It is believed to act mainly by preventing the release of norepinephrine at nerve endings and causes depletion of norepinephrine in peripheral sympathetic nerve terminals as well as in tissues. [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] Guinea Pigs: A common name used for the family Caviidae. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research. [NIH]
Habitual: Of the nature of a habit; according to habit; established by or repeated by force of habit, customary. [EU] Haematoma: A localized collection of blood, usually clotted, in an organ, space, or tissue, due to a break in the wall of a blood vessel. [EU] Haemodialysis: The removal of certain elements from the blood by virtue of the difference in the rates of their diffusion through a semipermeable membrane, e.g., by means of a haemodialyzer. [EU] Half-Life: The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. [NIH] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH] Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH]
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Headache Disorders: Common conditions characterized by persistent or recurrent headaches. Headache syndrome classification systems may be based on etiology (e.g., vascular headache, post-traumatic headaches, etc.), temporal pattern (e.g., cluster headache, paroxysmal hemicrania, etc.), and precipitating factors (e.g., cough headache). [NIH] Head-Down Tilt: Posture while lying with the head lower than the rest of the body. Extended time in this position is associated with temporary physiologic disturbances. [NIH] Health Care Costs: The actual costs of providing services related to the delivery of health care, including the costs of procedures, therapies, and medications. It is differentiated from health expenditures, which refers to the amount of money paid for the services, and from fees, which refers to the amount charged, regardless of cost. [NIH] Health Expenditures: The amounts spent by individuals, groups, nations, or private or public organizations for total health care and/or its various components. These amounts may or may not be equivalent to the actual costs (health care costs) and may or may not be shared among the patient, insurers, and/or employers. [NIH] Health Status: The level of health of the individual, group, or population as subjectively assessed by the individual or by more objective measures. [NIH] Heart Arrest: Sudden and usually momentary cessation of the heart beat. This sudden cessation may, but not usually, lead to death, sudden, cardiac. [NIH] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Heartbeat: One complete contraction of the heart. [NIH] Hematemesis: Vomiting of blood. [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] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemicrania: An ache or a pain in one side of the head, as in migraine. [NIH] Hemin: Chloro(7,12-diethenyl-3,8,13,17-tetramethyl-21H,23H-porphine-2,18dipropanoato(4-)-N(21),N(22),N(23),N(24)) ferrate(2-) dihydrogen. [NIH] Hemiplegia: Severe or complete loss of motor function on one side of the body. This condition is usually caused by BRAIN DISEASES that are localized to the cerebral hemisphere opposite to the side of weakness. Less frequently, BRAIN STEM lesions; cervical spinal cord diseases; peripheral nervous system diseases; and other conditions may manifest as hemiplegia. The term hemiparesis (see paresis) refers to mild to moderate weakness involving one side of the body. [NIH] 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] Hemodialyzer: Apparatus for hemodialysis performing the functions of human kidneys in
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place of the damaged organs; highly specialized medical equipment used for treating kidney failure by passing the body's toxic substances through an external artificial kidney. [NIH] Hemodilution: Reduction of blood viscosity usually by the addition of cell free solutions. Used clinically l) in states of impaired microcirculation, 2) for replacement of intraoperative blood loss without homologous blood transfusion, and 3) in cardiopulmonary bypass and hypothermia. [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] Hemoglobin A: Normal adult human hemoglobin. The globin moiety consists of two alpha and two beta chains. [NIH] Hemoglobinuria: The presence of free hemoglobin in the urine. [NIH] Hemolysins: Substances, usually of biological origin, that destroy blood cells; they may be antibodies or other immunologic factors, toxins, enzymes, etc.; hemotoxins are toxic to blood in general, including the clotting mechanism; hematotoxins may refer to the hematopoietic system. [NIH] Hemolysis: The destruction of erythrocytes by many different causal agents such as antibodies, bacteria, chemicals, temperature, and changes in tonicity. [NIH] Hemolytic: A disease that affects the blood and blood vessels. It destroys red blood cells, cells that cause the blood to clot, and the lining of blood vessels. HUS is often caused by the Escherichia coli bacterium in contaminated food. People with HUS may develop acute renal failure. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemostasis: The process which spontaneously arrests the flow of blood from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation. [NIH]
Hepatic: Refers to the liver. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatocytes: The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. [NIH] 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]
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Heritability: The proportion of observed variation in a particular trait that can be attributed to inherited genetic factors in contrast to environmental ones. [NIH] Heterodimers: Zippered pair of nonidentical proteins. [NIH] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]
Histamine: 1H-Imidazole-4-ethanamine. A depressor amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. [NIH] Histidine: An essential amino acid important in a number of metabolic processes. It is required for the production of histamine. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Homogeneous: Consisting of or composed of similar elements or ingredients; of a uniform quality throughout. [EU] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] 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] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hybridomas: Cells artificially created by fusion of activated lymphocytes with neoplastic cells. The resulting hybrid cells are cloned and produce pure or "monoclonal" antibodies or T-cell products, identical to those produced by the immunologically competent parent, and continually grow and divide as the neoplastic parent. [NIH] Hydralazine: A direct-acting vasodilator that is used as an antihypertensive agent. [NIH] Hydration: Combining with water. [NIH] Hydrocortisone: The main glucocorticoid secreted by the adrenal cortex. Its synthetic counterpart is used, either as an injection or topically, in the treatment of inflammation, allergy, collagen diseases, asthma, adrenocortical deficiency, shock, and some neoplastic 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 Cyanide: HCN. A toxic liquid or colorless gas. It is found in the smoke of various tobacco products and released by combustion of nitrogen-containing organic materials. [NIH]
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Hydrogen Peroxide: A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydrophilic: Readily absorbing moisture; hygroscopic; having strongly polar groups that readily interact with water. [EU] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU] Hydroxyzine: A histamine H1 receptor antagonist that is effective in the treatment of chronic urticaria, dermatitis, and histamine-mediated pruritus. Unlike its major metabolite cetirizine, it does cause drowsiness. It is also effective as an antiemetic, for relief of anxiety and tension, and as a sedative. [NIH] Hyperalgesia: Excessive sensitiveness or sensibility to pain. [EU] Hyperbilirubinemia: Pathologic process consisting of an abnormal increase in the amount of bilirubin in the circulating blood, which may result in jaundice. [NIH] Hypercalcemia: Abnormally high level of calcium in the blood. [NIH] Hypercapnia: A clinical manifestation of abnormal increase in the amount of carbon dioxide in arterial blood. [NIH] Hypercarbia: Excess of carbon dioxide in the blood. [NIH] Hypercholesterolemia: Abnormally high levels of cholesterol in the blood. [NIH] Hyperglycemia: Abnormally high blood sugar. [NIH] Hyperhomocysteinemia: An inborn error of methionone metabolism which produces an excess of homocysteine in the blood. It is often caused by a deficiency of cystathionine betasynthase and is a risk factor for coronary vascular disease. [NIH] Hyperlipidemia: An excess of lipids in the blood. [NIH] 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] Hypersensitivity, Immediate: Hypersensitivity reactions which occur within minutes of exposure to challenging antigen due to the release of histamine which follows the antigenantibody reaction and causes smooth muscle contraction and increased vascular permeability. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hyperthermia: A type of treatment in which body tissue is exposed to high temperatures to damage and kill cancer cells or to make cancer cells more sensitive to the effects of radiation and certain anticancer drugs. [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] 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]
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Hyperuricemia: A buildup of uric acid (a byproduct of metabolism) in the blood; a side effect of some anticancer drugs. [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] Hypesthesia: Absent or reduced sensitivity to cutaneous stimulation. [NIH] Hypnotic: A drug that acts to induce sleep. [EU] Hypoglycaemia: An abnormally diminished concentration of glucose in the blood, which may lead to tremulousness, cold sweat, piloerection, hypothermia, and headache, accompanied by irritability, confusion, hallucinations, bizarre behaviour, and ultimately, 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] Hypokinesia: Slow or diminished movement of body musculature. It may be associated with basal ganglia diseases; mental disorders; prolonged inactivity due to illness; experimental protocols used to evaluate the physiologic effects of immobility; and other conditions. [NIH] Hypophysis: A remnant of the entodermal pouch of Rathke beneath the mucous membrane of the pharynx, which shows pituitary tissue. [NIH] Hypotension: Abnormally low blood pressure. [NIH] Hypotensive: Characterized by or causing diminished tension or pressure, as abnormally low blood pressure. [EU] 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] Hypovolaemia: Abnormally decreased volume of circulating fluid (plasma) in the body. [EU] Hypovolemia: An abnormally low volume of blood circulating through the body. It may result in hypovolemic shock. [NIH] Hypoxemia: Deficient oxygenation of the blood; hypoxia. [EU] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU] Hysterotomy: An incision in the uterus, performed through either the abdomen or the vagina. [NIH] 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] Illusion: A false interpretation of a genuine percept. [NIH] Imaging procedures: Methods of producing pictures of areas inside the body. [NIH]
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Imidazole: C3H4N2. The ring is present in polybenzimidazoles. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]
Immune Sera: Serum that contains antibodies. It is obtained from an animal that has been immunized either by antigen injection or infection with microorganisms containing the antigen. [NIH] Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunity: Nonsusceptibility to the invasive or pathogenic microorganisms or to the toxic effect of antigenic substances. [NIH]
effects
of
foreign
Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunoassay: Immunochemical assay or detection of a substance by serologic or immunologic methods. Usually the substance being studied serves as antigen both in antibody production and in measurement of antibody by the test substance. [NIH] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunogenic: Producing immunity; evoking an immune response. [EU] Immunoglobulin: A protein that acts as an antibody. [NIH] Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunologic Factors: Biologically active substances whose activities affect or play a role in the functioning of the immune system. [NIH] Immunology: The study of the body's immune system. [NIH] Immunophilin: A drug for the treatment of Parkinson's disease. [NIH] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Implant radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called [NIH] Implantation: The insertion or grafting into the body of biological, living, inert, or radioactive material. [EU] Impotence: The inability to perform sexual intercourse. [NIH] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes. [NIH] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH]
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In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH] Incontinence: Inability to control the flow of urine from the bladder (urinary incontinence) or the escape of stool from the rectum (fecal incontinence). [NIH] Incubation: The development of an infectious disease from the entrance of the pathogen to the appearance of clinical symptoms. [EU] Incubation period: The period of time likely to elapse between exposure to the agent of the disease and the onset of clinical symptoms. [NIH] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infancy: The period of complete dependency prior to the acquisition of competence in walking, talking, and self-feeding. [NIH] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]
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] Inhalation: The drawing of air or other substances into the lungs. [EU] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Inlay: In dentistry, a filling first made to correspond with the form of a dental cavity and then cemented into the cavity. [NIH] Inner ear: The labyrinth, comprising the vestibule, cochlea, and semicircular canals. [NIH]
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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] Inoculum: The spores or tissues of a pathogen that serve to initiate disease in a plant. [NIH] Inoperable: Not suitable to be operated upon. [EU] Inorganic: Pertaining to substances not of organic origin. [EU] 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, genetic, and environmental factors are involved in the development of type I diabetes. [NIH] Integrins: A family of transmembrane glycoproteins consisting of noncovalent heterodimers. They interact with a wide variety of ligands including extracellular matrix glycoproteins, complement, and other cells, while their intracellular domains interact with the cytoskeleton. The integrins consist of at least three identified families: the cytoadhesin receptors, the leukocyte adhesion receptors, and the very-late-antigen receptors. Each family contains a common beta-subunit combined with one or more distinct alpha-subunits. These receptors participate in cell-matrix and cell-cell adhesion in many physiologically important processes, including embryological development, hemostasis, thrombosis, wound healing, immune and nonimmune defense mechanisms, and oncogenic transformation. [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] Interferon: A biological response modifier (a substance that can improve the body's natural response to disease). Interferons interfere with the division of cancer cells and can slow tumor growth. There are several types of interferons, including interferon-alpha, -beta, and gamma. These substances are normally produced by the body. They are also made in the laboratory for use in treating cancer and other diseases. [NIH] Interferon-alpha: One of the type I interferons produced by peripheral blood leukocytes or lymphoblastoid cells when exposed to live or inactivated virus, double-stranded RNA, or bacterial products. It is the major interferon produced by virus-induced leukocyte cultures and, in addition to its pronounced antiviral activity, it causes activation of NK cells. [NIH] Interindividual: Occurring between two or more individuals. [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
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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-3: A multilineage cell growth factor secreted by lymphocytes, epithelial cells, and astrocytes which stimulates clonal proliferation and differentiation of various types of blood and tissue cells. Also called multi-CSF, it is considered one of the hematopoietic colony stimulating factors. [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] Interleukin-8: A cytokine that activates neutrophils and attracts neutrophils and Tlymphocytes. It is released by several cell types including monocytes, macrophages, Tlymphocytes, fibroblasts, endothelial cells, and keratinocytes by an inflammatory stimulus. IL-8 is a member of the beta-thromboglobulin superfamily and structurally related to platelet factor 4. [NIH] Interleukins: Soluble factors which stimulate growth-related activities of leukocytes as well as other cell types. They enhance cell proliferation and differentiation, DNA synthesis, secretion of other biologically active molecules and responses to immune and inflammatory stimuli. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Internal Medicine: A medical specialty concerned with the diagnosis and treatment of diseases of the internal organ systems of adults. [NIH] Internal radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called brachytherapy, implant radiation, or interstitial radiation therapy. [NIH] Interpersonal Relations: The reciprocal interaction of two or more persons. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intervertebral: Situated between two contiguous vertebrae. [EU] Intervertebral Disk Displacement: An intervertebral disk in which the nucleus pulposus has protruded through surrounding fibrocartilage. This occurs most frequently in the lower lumbar region. [NIH] Intestinal: Having to do with the intestines. [NIH] Intestines: The section of the alimentary canal from the stomach to the anus. It includes the large intestine and small intestine. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intracellular Membranes: Membranes of subcellular structures. [NIH] Intracranial Aneurysm: A saclike dilatation of the walls of a blood vessel, usually an artery. [NIH]
Intracranial Arteriosclerosis: Vascular diseases characterized by thickening, hardening, and remodeling of the walls of intracranial arteries. There are three subtypes: (1) atherosclerosis,
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marked by fatty depositions in the innermost layer of the arterial walls, (2) Monckeberg's sclerosis, which features calcium deposition in the media and (3) arteriolosclerosis, which refers to sclerosis of small caliber arteries. Clinically, this process may be associated with transient ischemic attack, brain infarction, intracranial embolism and thrombosis, or intracranial aneurysm. [NIH] Intracranial Hypertension: Increased pressure within the cranial vault. This may result from several conditions, including hydrocephalus; brain edema; intracranial masses; severe systemic hypertension; pseudotumor cerebri; and other disorders. [NIH] Intracranial Hypotension: A condition in which there is a diminution or loss of muscular tonicity, in consequence of which the muscles may be stretched beyond their normal limits. [NIH]
Intracranial Pressure: Pressure within the cranial cavity. It is influenced by brain mass, the circulatory system, CSF dynamics, and skull rigidity. [NIH] Intramuscular: IM. Within or into muscle. [NIH] Intraocular: Within the eye. [EU] Intraocular pressure: Pressure of the fluid inside the eye; normal IOP varies among individuals. [NIH] Intrathecal: Describes the fluid-filled space between the thin layers of tissue that cover the brain and spinal cord. Drugs can be injected into the fluid or a sample of the fluid can be removed for testing. [NIH] Intravascular: Within a vessel or vessels. [EU] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Intubation: Introduction of a tube into a hollow organ to restore or maintain patency if obstructed. It is differentiated from catheterization in that the insertion of a catheter is usually performed for the introducing or withdrawing of fluids from the body. [NIH] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]
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] Ionizing: Radiation comprising charged particles, e. g. electrons, protons, alpha-particles, etc., having sufficient kinetic energy to produce ionization by collision. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Irinotecan: An anticancer drug that belongs to a family of anticancer drugs called topoisomerase inhibitors. It is a camptothecin analogue. Also called CPT 11. [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
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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] Isoflurane: A stable, non-explosive inhalation anesthetic, relatively free from significant side effects. [NIH] Isolated limb perfusion: A technique that may be used to deliver anticancer drugs directly to an arm or leg. The flow of blood to and from the limb is temporarily stopped with a tourniquet, and anticancer drugs are put directly into the blood of the limb. This allows the person to receive a high dose of drugs in the area where the cancer occurred. [NIH] Isoproterenol: Isopropyl analog of epinephrine; beta-sympathomimetic that acts on the heart, bronchi, skeletal muscle, alimentary tract, etc. It is used mainly as bronchodilator and heart stimulant. [NIH] Ixodes: A large, widely distributed genus of ticks consisting of approximately 245 species. Many infest man and other mammals and several are vectors of diseases such as Lyme disease, tick-borne encephalitis (encephalitis, tick-borne), and Kyasanur forest disease. [NIH] Jaundice: A clinical manifestation of hyperbilirubinemia, consisting of deposition of bile pigments in the skin, resulting in a yellowish staining of the skin and mucous membranes. [NIH]
Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [NIH] Kallidin: A decapeptide bradykinin homolog produced by the action of tissue and glandular kallikreins on low-molecular-weight kininogen. It is a smooth-muscle stimulant and hypotensive agent that functions through vasodilatation. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Keratinocytes: Epidermal cells which synthesize keratin and undergo characteristic changes as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. Successive stages of differentiation of the keratinocytes forming the epidermal layers are basal cell, spinous or prickle cell, and the granular cell. [NIH] Ketamine: A cyclohexanone derivative used for induction of anesthesia. Its mechanism of action is not well understood, but ketamine can block NMDA receptors (receptors, NMethyl-D-Aspartate) and may interact with sigma receptors. [NIH] Ketone Bodies: Chemicals that the body makes when there is not enough insulin in the blood and it must break down fat for its energy. Ketone bodies can poison and even kill body cells. When the body does not have the help of insulin, the ketones build up in the blood and then "spill" over into the urine so that the body can get rid of them. The body can also rid itself of one type of ketone, called acetone, through the lungs. This gives the breath a fruity odor. Ketones that build up in the body for a long time lead to serious illness and coma. [NIH] Ketorolac: A drug that belongs to a family of drugs called nonsteroidal anti-inflammatory agents. It is being studied in cancer prevention. [NIH] Ketosis: A condition of having ketone bodies build up in body tissues and fluids. The signs
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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] Labyrinth: The internal ear; the essential part of the organ of hearing. It consists of an osseous and a membranous portion. [NIH] Labyrinthine: A vestibular nystagmus resulting from stimulation, injury, or disease of the labyrinth. [NIH] Labyrinthitis: Inflammation of the inner ear. [NIH] Laceration: 1. The act of tearing. 2. A torn, ragged, mangled wound. [EU] Lactation: The period of the secretion of milk. [EU] Lactose Intolerance: The disease state resulting from the absence of lactase enzyme in the musocal cells of the gastrointestinal tract, and therefore an inability to break down the disaccharide lactose in milk for absorption from the gastrointestinal tract. It is manifested by indigestion of a mild nature to severe diarrhea. It may be due to inborn defect genetically conditioned or may be acquired. [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] Latency: The period of apparent inactivity between the time when a stimulus is presented and the moment a response occurs. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Laterality: Behavioral manifestations of cerebral dominance in which there is preferential use and superior functioning of either the left or the right side, as in the preferred use of the
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right hand or right foot. [NIH] Lavage: A cleaning of the stomach and colon. Uses a special drink and enemas. [NIH] Lectin: A complex molecule that has both protein and sugars. Lectins are able to bind to the outside of a cell and cause biochemical changes in it. Lectins are made by both animals and plants. [NIH] Lens: The transparent, double convex (outward curve on both sides) structure suspended between the aqueous and vitreous; helps to focus light on the retina. [NIH] Leprosy: A chronic granulomatous infection caused by Mycobacterium leprae. The granulomatous lesions are manifested in the skin, the mucous membranes, and the peripheral nerves. Two polar or principal types are lepromatous and tuberculoid. [NIH] Leptin: A 16-kD peptide hormone secreted from white adipocytes and implicated in the regulation of food intake and energy balance. Leptin provides the key afferent signal from fat cells in the feedback system that controls body fat stores. [NIH] Leptospirosis: Infections with bacteria of the genus Leptospira. [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]
Leukemia: Cancer of blood-forming tissue. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Leukopenia: A condition in which the number of leukocytes (white blood cells) in the blood is reduced. [NIH] Leukotrienes: A family of biologically active compounds derived from arachidonic acid by oxidative metabolism through the 5-lipoxygenase pathway. They participate in host defense reactions and pathophysiological conditions such as immediate hypersensitivity and inflammation. They have potent actions on many essential organs and systems, including the cardiovascular, pulmonary, and central nervous system as well as the gastrointestinal tract and the immune system. [NIH] Levodopa: The naturally occurring form of dopa and the immediate precursor of dopamine. Unlike dopamine itself, it can be taken orally and crosses the blood-brain barrier. It is rapidly taken up by dopaminergic neurons and converted to dopamine. It is used for the treatment of parkinsonism and is usually given with agents that inhibit its conversion to dopamine outside of the central nervous 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] Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] Ligands: A RNA simulation method developed by the MIT. [NIH] Ligation: Application of a ligature to tie a vessel or strangulate a part. [NIH] Limb perfusion: A technique that may be used to deliver anticancer drugs directly to an
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arm or leg. The flow of blood to and from the limb is temporarily stopped with a tourniquet, and anticancer drugs are put directly into the blood of the limb. This allows the person to receive a high dose of drugs in the area where the cancer occurred. [NIH] Lincomycin: (2S-trans)-Methyl 6,8-dideoxy-6-(((1-methyl-4-propyl-2pyrrolidinyl)carbonyl)amino)-1-thio-D-erythro-alpha-D-galacto-octopyranoside. An antibiotic produced by Streptomyces lincolnensis var. lincolnensis. It has been used in the treatment of staphylococcal, streptococcal, and Bacteroides fragilis infections. [NIH] Linkages: 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 Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] Lipopolysaccharide: 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] Lipoxygenase: An enzyme of the oxidoreductase class that catalyzes reactions between linoleate and other fatty acids and oxygen to form hydroperoxy-fatty acid derivatives. Related enzymes in this class include the arachidonate lipoxygenases, arachidonate 5lipoxygenase, arachidonate 12-lipoxygenase, and arachidonate 15-lipoxygenase. EC 1.13.11.12. [NIH] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [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] Locus Coeruleus: Bluish region in the superior angle of the fourth ventricle floor, corresponding to melanin-like pigmented nerve cells which lie lateral to the pontomesencephalic central gray (griseum centrale). It is also known as nucleus pigmentosus pontis. [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] Lordosis: The anterior concavity in the curvature of the lumbar and cervical spine as viewed from the side. The term usually refers to abnormally increased curvature (hollow back, saddle back, swayback). It does not include lordosis as normal mating posture in certain animals ( = posture + sex behavior, animal). [NIH] Low Back Pain: Acute or chronic pain in the lumbar or sacral regions, which may be associated with musculo-ligamentous sprains and strains; intervertebral disk displacement; and other conditions. [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]
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Lumbar: Pertaining to the loins, the part of the back between the thorax and the pelvis. [EU] Lumen: The cavity or channel within a tube or tubular organ. [EU] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]
Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lymphokines: Soluble protein factors generated by activated lymphocytes that affect other cells, primarily those involved in cellular immunity. [NIH] Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [NIH] Lytic: 1. Pertaining to lysis or to a lysin. 2. Producing lysis. [EU] 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] Macrophage Colony-Stimulating Factor: A mononuclear phagocyte colony-stimulating factor synthesized by mesenchymal cells. The compound stimulates the survival, proliferation, and differentiation of hematopoietic cells of the monocyte-macrophage series. M-CSF is a disulfide-bonded glycoprotein dimer with a MW of 70 kDa. It binds to a specific high affinity receptor (receptor, macrophage colony-stimulating factor). [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] 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] Malabsorption: Impaired intestinal absorption of nutrients. [EU] Malaise: A vague feeling of bodily discomfort. [EU] Malignancy: A cancerous tumor that can invade and destroy nearby tissue and spread to other parts of the body. [NIH]
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Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]
Mammary: Pertaining to the mamma, or breast. [EU] Mammogram: An x-ray of the breast. [NIH] Mania: Excitement of psychotic proportions manifested by mental and physical hyperactivity, disorganization of behaviour, and elevation of mood. [EU] Manic: Affected with mania. [EU] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] Mannitol: A diuretic and renal diagnostic aid related to sorbitol. It has little significant energy value as it is largely eliminated from the body before any metabolism can take place. It can be used to treat oliguria associated with kidney failure or other manifestations of inadequate renal function and has been used for determination of glomerular filtration rate. Mannitol is also commonly used as a research tool in cell biological studies, usually to control osmolarity. [NIH] Mastication: The act and process of chewing and grinding food in the mouth. [NIH] Mastocytosis: A group of diseases resulting from proliferation of mast cells. [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]
Meconium: The thick green-to-black mucilaginous material found in the intestines of a fullterm fetus. It consists of secretions of the intestinal glands, bile pigments, fatty acids, amniotic fluid, and intrauterine debris. It constitutes the first stools passed by a newborn. [NIH]
Meconium Aspiration: Syndrome caused by sucking of thick meconium into the lungs, usually by term or post-term infants (often small for gestational age) either in utero or with first breath. The resultant small airway obstruction may produce respiratory distress, tachypnea, cyanosis, pneumothorax, and/or pneumomediastinum. [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] 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] Meiosis: A special method of cell division, occurring in maturation of the germ cells, by
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means of which each daughter nucleus receives half the number of chromosomes characteristic of the somatic cells of the species. [NIH] Melanin: The substance that gives the skin its color. [NIH] Melanocytes: Epidermal dendritic pigment cells which control long-term morphological color changes by alteration in their number or in the amount of pigment they produce and store in the pigment containing organelles called melanosomes. Melanophores are larger cells which do not exist in mammals. [NIH] Melanoma: A form of skin cancer that arises in melanocytes, the cells that produce pigment. Melanoma usually begins in a mole. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells. [NIH] Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Meningeal: Refers to the meninges, the tissue covering the brain and spinal cord. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Menstrual Cycle: The period of the regularly recurring physiologic changes in the endometrium occurring during the reproductive period in human females and some primates and culminating in partial sloughing of the endometrium (menstruation). [NIH] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH] Mental 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]
Mentors: Senior professionals who provide guidance, direction and support to those persons desirous of improvement in academic positions, administrative positions or other career development situations. [NIH] Mesencephalic: Ipsilateral oculomotor paralysis and contralateral tremor, spasm. or choreic movements of the face and limbs. [NIH] Mesenteric: Pertaining to the mesentery : a membranous fold attaching various organs to the body wall. [EU] Mesentery: A layer of the peritoneum which attaches the abdominal viscera to the abdominal wall and conveys their blood vessels and nerves. [NIH] Meta-Analysis: A quantitative method of combining the results of independent studies (usually drawn from the published literature) and synthesizing summaries and conclusions which may be used to evaluate therapeutic effectiveness, plan new studies, etc., with application chiefly in the areas of research and medicine. [NIH] Metabolic disorder: A condition in which normal metabolic processes are disrupted,
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usually because of a missing enzyme. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors" and contain cells that are like those in the original (primary) tumor. The plural is metastases. [NIH] Metastatic: Having to do with metastasis, which is the spread of cancer from one part of the body to another. [NIH] Methionine: A sulfur containing essential amino acid that is important in many body functions. It is a chelating agent for heavy metals. [NIH] Methyltransferase: A drug-metabolizing enzyme. [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microcalcifications: Tiny deposits of calcium in the breast that cannot be felt but can be detected on a mammogram. A cluster of these very small specks of calcium may indicate that cancer is present. [NIH] Microcirculation: The vascular network lying between the arterioles and venules; includes capillaries, metarterioles and arteriovenous anastomoses. Also, the flow of blood through this network. [NIH] Microdialysis: A technique for measuring extracellular concentrations of substances in tissues, usually in vivo, by means of a small probe equipped with a semipermeable membrane. Substances may also be introduced into the extracellular space through the membrane. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Microtubules: Slender, cylindrical filaments found in the cytoskeleton of plant and animal cells. They are composed of the protein tubulin. [NIH] Midodrine: An ethanolamine derivative that is an adrenergic alpha agonist. It is used as a vasoconstrictor agent in the treatment of hypotension. [NIH] Milk Hypersensitivity: Allergic reaction to milk (usually cow's milk) or milk products. In infants the hypersensitivity is manifested by colic, vomiting, diarrhea, rhinitis, wheezing, etc. Milk hypersensitivity should be differentiated from lactose intolerance, an intolerance to milk as a result of congenital deficiency of lactase. [NIH] Mineralocorticoid: 1. Any of the group of C21 corticosteroids, principally aldosterone, predominantly involved in the regulation of electrolyte and water balance through their effect on ion transport in epithelial cells of the renal tubules, resulting in retention of sodium and loss of potassium; some also possess varying degrees of glucocorticoid activity. Their secretion is regulated principally by plasma volume, serum potassium concentration and angiotensin II, and to a lesser extent by anterior pituitary ACTH. 2. Of, pertaining to, having
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the properties of, or resembling a mineralocorticoid. [EU] 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] 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] 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] 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] Monokines: Soluble mediators of the immune response that are neither antibodies nor complement. They are produced largely, but not exclusively, by monocytes and macrophages. [NIH] Mononeuropathies: Disease or trauma involving a single peripheral nerve in isolation, or out of proportion to evidence of diffuse peripheral nerve dysfunction. Mononeuropathy multiplex refers to a condition characterized by multiple isolated nerve injuries. Mononeuropathies may result from a wide variety of causes, includingischemia; traumatic injury; compression; connective tissue diseases; cumulative trauma disorders; and other conditions. [NIH] Mononuclear: A cell with one nucleus. [NIH] Monophosphate: So called second messenger for neurotransmitters and hormones. [NIH] Morphine: The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle. [NIH] Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Motility: The ability to move spontaneously. [EU] Motion Sickness: Sickness caused by motion, as sea sickness, train sickness, car sickness, and air sickness. [NIH] Motor nerve: An efferent nerve conveying an impulse that excites muscular contraction. [NIH]
Movement Disorders: Syndromes which feature dyskinesias as a cardinal manifestation of the disease process. Included in this category are degenerative, hereditary, post-infectious,
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medication-induced, post-inflammatory, and post-traumatic conditions. [NIH] Mucilaginous: Pertaining to or secreting mucus. [NIH] Mucinous: Containing or resembling mucin, the main compound in mucus. [NIH] Mucins: A secretion containing mucopolysaccharides and protein that is the chief constituent of mucus. [NIH] Mucosa: A mucous membrane, or tunica mucosa. [EU] Multiple Organ Failure: A progressive condition usually characterized by combined failure of several organs such as the lungs, liver, kidney, along with some clotting mechanisms, usually postinjury or postoperative. [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] Multiple Trauma: Physical insults or injuries occurring simultaneously in several parts of the body. [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 relaxant: An agent that specifically aids in reducing muscle tension, as those acting at the polysynaptic neurons of motor nerves (e.g. meprobamate) or at the myoneural junction (curare and related compounds). [EU] Muscle Relaxation: That phase of a muscle twitch during which a muscle returns to a resting position. [NIH] Muscular Atrophy: Derangement in size and number of muscle fibers occurring with aging, reduction in blood supply, or following immobilization, prolonged weightlessness, malnutrition, and particularly in denervation. [NIH] Muscular Dystrophies: A general term for a group of inherited disorders which are characterized by progressive degeneration of skeletal muscles. [NIH] Mutagenesis: Process of generating genetic mutations. It may occur spontaneously or be induced by mutagens. [NIH] Mutagenic: Inducing genetic mutation. [EU] Mutagens: Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. [NIH] Myalgia: Pain in a muscle or muscles. [EU] Myasthenia: Muscular debility; any constitutional anomaly of muscle. [EU] Mydriatic: 1. Dilating the pupil. 2. Any drug that dilates the pupil. [EU] Myelin: The fatty substance that covers and protects nerves. [NIH] Myelography: X-ray visualization of the spinal cord following injection of contrast medium into the spinal arachnoid space. [NIH] Myelosuppression: A condition in which bone marrow activity is decreased, resulting in
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fewer red blood cells, white blood cells, and platelets. Myelosuppression is a side effect of some cancer treatments. [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] Myosin: Chief protein in muscle and the main constituent of the thick filaments of muscle fibers. In conjunction with actin, it is responsible for the contraction and relaxation of muscles. [NIH] Myotonic Dystrophy: A condition presenting muscle weakness and wasting which may be progressive. [NIH] Narcolepsy: A condition of unknown cause characterized by a periodic uncontrollable tendency to fall asleep. [NIH] Narcosis: A general and nonspecific reversible depression of neuronal excitability, produced by a number of physical and chemical aspects, usually resulting in stupor. [NIH] Narcotic: 1. Pertaining to or producing narcosis. 2. An agent that produces insensibility or stupor, applied especially to the opioids, i.e. to any natural or synthetic drug that has morphine-like actions. [EU] Nasal Mucosa: The mucous membrane lining the nasal cavity. [NIH] Nasogastric: The process of passing a small, flexible plastic tube through the nose or mouth into the stomach or small intestine. [NIH] Natriuresis: The excretion of abnormal amounts of sodium in the urine. [EU]
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Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU] Neoplasia: Abnormal and uncontrolled cell growth. [NIH] Neoplasms: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms. [NIH] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] Neostigmine: A cholinesterase inhibitor used in the treatment of myasthenia gravis and to reverse the effects of muscle relaxants such as gallamine and tubocurarine. Neostigmine, unlike physostigmine, does not cross the blood-brain barrier. [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] 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] Nephropathy: Disease of the kidneys. [EU] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nerve Endings: Specialized terminations of peripheral neurons. Nerve endings include neuroeffector junction(s) by which neurons activate target organs and sensory receptors which transduce information from the various sensory modalities and send it centrally in the nervous system. Presynaptic nerve endings are presynaptic terminals. [NIH] Nerve Fibers: Slender processes of neurons, especially the prolonged axons that conduct nerve impulses. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Networks: Pertaining to a nerve or to the nerves, a meshlike structure of interlocking fibers or strands. [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] Neural Pathways: Neural tracts connecting one part of the nervous system with another. [NIH]
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Neuralgia: Intense or aching pain that occurs along the course or distribution of a peripheral or cranial nerve. [NIH] Neuritis: A general term indicating inflammation of a peripheral or cranial nerve. Clinical manifestation may include pain; paresthesias; paresis; or hypesthesia. [NIH] Neuroanatomy: Study of the anatomy of the nervous system as a specialty or discipline. [NIH]
Neurodegenerative Diseases: Hereditary and sporadic conditions which are characterized by progressive nervous system dysfunction. These disorders are often associated with atrophy of the affected central or peripheral nervous system structures. [NIH] Neuroeffector Junction: The synapse between a neuron (presynaptic) and an effector cell other than another neuron (postsynaptic). Neuroeffector junctions include synapses onto muscles and onto secretory cells. [NIH] Neuroendocrine: Having to do with the interactions between the nervous system and the endocrine system. Describes certain cells that release hormones into the blood in response to stimulation of the nervous system. [NIH] Neuroendocrinology: The study of the anatomical and functional relationships between the nervous system and the endocrine system. [NIH] Neurogenic: Loss of bladder control caused by damage to the nerves controlling the bladder. [NIH] Neurologic: Having to do with nerves or the nervous system. [NIH] Neurologist: A doctor who specializes in the diagnosis and treatment of disorders of the nervous system. [NIH] Neuroma: A tumor that arises in nerve cells. [NIH] Neuromuscular: Pertaining to muscles and nerves. [EU] Neuromuscular Blockade: The intentional interruption of transmission at the neuromuscular junction by external agents, usually neuromuscular blocking agents. It is distinguished from nerve block in which nerve conduction is interrupted rather than neuromuscular transmission. Neuromuscular blockade is commonly used to produce muscle relaxation as an adjunct to anesthesia during surgery and other medical procedures. It is also often used as an experimental manipulation in basic research. It is not strictly speaking anesthesia but is grouped here with anesthetic techniques. The failure of neuromuscular transmission as a result of pathological processes is not included here. [NIH] 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] Neurophysiology: The scientific discipline concerned with the physiology of the nervous system. [NIH] Neurosis: Functional derangement due to disorders of the nervous system which does not affect the psychic personality of the patient. [NIH] Neurosurgeon: A doctor who specializes in surgery on the brain, spine, and other parts of the nervous system. [NIH]
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Neurotoxic: Poisonous or destructive to nerve tissue. [EU] Neurotoxicity: The tendency of some treatments to cause damage to 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] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] Neutropenia: An abnormal decrease in the number of neutrophils, a type of white blood cell. [NIH] Neutrophil: A type of white blood cell. [NIH] Nimodipine: A calcium channel blockader with preferential cerebrovascular activity. It has marked cerebrovascular dilating effects and lowers blood pressure. [NIH] Nitrates: Inorganic or organic salts and esters of nitric acid. These compounds contain the NO3- radical. [NIH] Nitric acid: A toxic, corrosive, colorless liquid used to make fertilizers, dyes, explosives, and other chemicals. [NIH] Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells. It is synthesized from arginine by a complex reaction, catalyzed by nitric oxide synthase. Nitric oxide is endothelium-derived relaxing factor. It is released by the vascular endothelium and mediates the relaxation induced by some vasodilators such as acetylcholine and bradykinin. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic GMP. [NIH]
Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] Nitrogen Oxides: Inorganic oxides that contain nitrogen. [NIH] Nitroglycerin: A highly volatile organic nitrate that acts as a dilator of arterial and venous smooth muscle and is used in the treatment of angina. It provides relief through improvement of the balance between myocardial oxygen supply and demand. Although total coronary blood flow is not increased, there is redistribution of blood flow in the heart when partial occlusion of coronary circulation is effected. [NIH] Nitroprusside: (OC-6-22)-Pentakis(cyano-C)nitrosoferrate(2-). A powerful vasodilator used in emergencies to lower blood pressure or to improve cardiac function. It is also an indicator for free sulfhydryl groups in proteins. [NIH] Nitrosamines: A class of compounds that contain a -NH2 and a -NO radical. Many members of this group have carcinogenic and mutagenic properties. [NIH] Non-small cell lung cancer: A group of lung cancers that includes squamous cell carcinoma, adenocarcinoma, and large cell carcinoma. [NIH]
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Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] Normotensive: 1. Characterized by normal tone, tension, or pressure, as by normal blood pressure. 2. A person with normal blood pressure. [EU] Nortriptyline: A metabolite of amitryptyline that is also used as an antidepressive agent. Nortriptyline is used in major depression, dysthymia, and atypical depressions. [NIH] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nursing Care: Care given to patients by nursing service personnel. [NIH] Nutritional Status: State of the body in relation to the consumption and utilization of nutrients. [NIH] Nystagmus: Rhythmical oscillation of the eyeballs, either pendular or jerky. [NIH] Obtundation: A dulled or reduced level of alertness or consciousness. [NIH] Octanes: Eight-carbon saturated hydrocarbon group of the methane series. Include isomers and derivatives. [NIH] Ocular: 1. Of, pertaining to, or affecting the eye. 2. Eyepiece. [EU] Ocular Hypotension: Abnormally low intraocular pressure often related to chronic inflammation (uveitis). [NIH] Odour: A volatile emanation that is perceived by the sense of smell. [EU] Oliguria: Clinical manifestation of the urinary system consisting of a decrease in the amount of urine secreted. [NIH] Omentum: A fold of the peritoneum (the thin tissue that lines the abdomen) that surrounds the stomach and other organs in the abdomen. [NIH] Oncogene: A gene that normally directs cell growth. If altered, an oncogene can promote or allow the uncontrolled growth of cancer. Alterations can be inherited or caused by an environmental exposure to carcinogens. [NIH] Oncogenic: Chemical, viral, radioactive or other agent that causes cancer; carcinogenic. [NIH] On-line: A sexually-reproducing population derived from a common parentage. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Ophthalmic: Pertaining to the eye. [EU] Opioid Peptides: The endogenous peptides with opiate-like activity. The three major classes currently recognized are the enkephalins, the dynorphins, and the endorphins. Each of these families derives from different precursors, proenkephalin, prodynorphin, and pro-
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opiomelanocortin, respectively. There are also at least three classes of opioid receptors, but the peptide families do not map to the receptors in a simple way. [NIH] Opium: The air-dried exudate from the unripe seed capsule of the opium poppy, Papaver somniferum, or its variant, P. album. It contains a number of alkaloids, but only a few morphine, codeine, and papaverine - have clinical significance. Opium has been used as an analgesic, antitussive, antidiarrheal, and antispasmodic. [NIH] Opportunistic Infections: An infection caused by an organism which becomes pathogenic under certain conditions, e.g., during immunosuppression. [NIH] Opsin: A protein formed, together with retinene, by the chemical breakdown of metarhodopsin. [NIH] Optic Chiasm: The X-shaped structure formed by the meeting of the two optic nerves. At the optic chiasm the fibers from the medial part of each retina cross to project to the other side of the brain while the lateral retinal fibers continue on the same side. As a result each half of the brain receives information about the contralateral visual field from both eyes. [NIH]
Optic Disk: The portion of the optic nerve seen in the fundus with the ophthalmoscope. It is formed by the meeting of all the retinal ganglion cell axons as they enter the optic nerve. [NIH]
Optic Nerve: The 2nd cranial nerve. The optic nerve conveys visual information from the retina to the brain. The nerve carries the axons of the retinal ganglion cells which sort at the optic chiasm and continue via the optic tracts to the brain. The largest projection is to the lateral geniculate nuclei; other important targets include the superior colliculi and the suprachiasmatic nuclei. Though known as the second cranial nerve, it is considered part of the central nervous system. [NIH] Oral Health: The optimal state of the mouth and normal functioning of the organs of the mouth without evidence of disease. [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] Orofacial: Of or relating to the mouth and face. [EU] Orthostatic: Pertaining to or caused by standing erect. [EU] Osmolarity: The concentration of osmotically active particles expressed in terms of osmoles of solute per litre of solution. [EU] Osmosis: Tendency of fluids (e.g., water) to move from the less concentrated to the more concentrated side of a semipermeable membrane. [NIH] Osmotic: Pertaining to or of the nature of osmosis (= the passage of pure solvent from a solution of lesser to one of greater solute concentration when the two solutions are separated by a membrane which selectively prevents the passage of solute molecules, but is permeable to the solvent). [EU] 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
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in a clinic or dispensary connected with the hospital. [NIH] Ovary: Either of the paired glands in the female that produce the female germ cells and secrete some of the female sex hormones. [NIH] Overactive bladder: A condition in which the patient experiences two or all three of the following conditions: [NIH] Overdose: An accidental or deliberate dose of a medication or street drug that is in excess of what is normally used. [NIH] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]
Oxidative metabolism: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as aerobic respiration, cell respiration, or aerobic metabolism. [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] Oxides: Binary compounds of oxygen containing the anion O(2-). The anion combines with metals to form alkaline oxides and non-metals to form acidic oxides. [NIH] Oximetry: The determination of oxygen-hemoglobin saturation of blood either by withdrawing a sample and passing it through a classical photoelectric oximeter or by electrodes attached to some translucent part of the body like finger, earlobe, or skin fold. It includes non-invasive oxygen monitoring by pulse oximetry. [NIH] Oxygen Consumption: The oxygen consumption is determined by calculating the difference between the amount of oxygen inhaled and exhaled. [NIH] Oxygenase: Enzyme which breaks down heme, the iron-containing oxygen-carrying constituent of the red blood cells. [NIH] Oxygenation: The process of supplying, treating, or mixing with oxygen. No:1245 oxygenation the process of supplying, treating, or mixing with oxygen. [EU] Oxygenator: An apparatus by which oxygen is introduced into the blood during circulation outside the body, as during open heart surgery. [NIH] Oxytocin: A nonapeptide posterior pituitary hormone that causes uterine contractions and stimulates lactation. [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] Paediatric: Of or relating to the care and medical treatment of children; belonging to or concerned with paediatrics. [EU]
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Pain, Postoperative: Pain during the period after surgery. [NIH] Palate: The structure that forms the roof of the mouth. It consists of the anterior hard palate and the posterior soft palate. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Palsy: Disease of the peripheral nervous system occurring usually after many years of increased lead absorption. [NIH] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreas Transplant: A surgical procedure that involves replacing the pancreas of a person who has diabetes with a healthy pancreas that can make insulin. The healthy pancreas comes from a donor who has just died or from a living relative. A person can donate half a pancreas and still live normally. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Pancreatic cancer: Cancer of the pancreas, a salivary gland of the abdomen. [NIH] Pancreatitis: Acute or chronic inflammation of the pancreas, which may be asymptomatic or symptomatic, and which is due to autodigestion of a pancreatic tissue by its own enzymes. It is caused most often by alcoholism or biliary tract disease; less commonly it may be associated with hyperlipaemia, hyperparathyroidism, abdominal trauma (accidental or operative injury), vasculitis, or uraemia. [EU] Panic: A state of extreme acute, intense anxiety and unreasoning fear accompanied by disorganization of personality function. [NIH] Panic Disorder: A type of anxiety disorder characterized by unexpected panic attacks that last minutes or, rarely, hours. Panic attacks begin with intense apprehension, fear or terror and, often, a feeling of impending doom. Symptoms experienced during a panic attack include dyspnea or sensations of being smothered; dizziness, loss of balance or faintness; choking sensations; palpitations or accelerated heart rate; shakiness; sweating; nausea or other form of abdominal distress; depersonalization or derealization; paresthesias; hot flashes or chills; chest discomfort or pain; fear of dying and fear of not being in control of oneself or going crazy. Agoraphobia may also develop. Similar to other anxiety disorders, it may be inherited as an autosomal dominant trait. [NIH] Paralysis: Loss of ability to move all or part of the body. [NIH] Parenchyma: The essential elements of an organ; used in anatomical nomenclature as a general term to designate the functional elements of an organ, as distinguished from its framework, or stroma. [EU] Parenteral: Not through the alimentary canal but rather by injection through some other route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intravenous, etc. [EU] Paresis: A general term referring to a mild to moderate degree of muscular weakness, occasionally used as a synonym for paralysis (severe or complete loss of motor function). In the older literature, paresis often referred specifically to paretic neurosyphilis. "General paresis" and "general paralysis" may still carry that connotation. Bilateral lower extremity paresis is referred to as paraparesis. [NIH] Paresthesias: Abnormal touch sensations, such as burning or prickling, that occur without an outside stimulus. [NIH]
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Parkinsonism: A group of neurological disorders characterized by hypokinesia, tremor, and muscular rigidity. [EU] Paroxetine: A serotonin uptake inhibitor that is effective in the treatment of depression. [NIH]
Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Particle: A tiny mass of material. [EU] Patch: A piece of material used to cover or protect a wound, an injured part, etc.: a patch over the eye. [NIH] Pathogen: Any disease-producing microorganism. [EU] 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 Education: The teaching or training of patients concerning their own health needs. [NIH]
Pediatric Nursing: The nursing care of children from birth to adolescence. It includes the clinical and psychological aspects of nursing care. [NIH] Pelvic: Pertaining to the pelvis. [EU] Penicillin: An antibiotic drug used to treat infection. [NIH] Penile Erection: The state of the penis when the erectile tissue becomes filled with blood and causes the penis to become rigid and elevated. [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] Peptic: Pertaining to pepsin or to digestion; related to the action of gastric juices. [EU] Peptic Ulcer: An ulceration of the mucous membrane of the esophagus, stomach or duodenum, caused by the action of the acid gastric juice. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Peptide T: N-(N-(N(2)-(N-(N-(N-(N-D-Alanyl L-seryl)-L-threonyl)-L-threonyl) L-threonyl)L-asparaginyl)-L-tyrosyl) L-threonine. Octapeptide sharing sequence homology with HIV envelope protein gp120. It is potentially useful as antiviral agent in AIDS therapy. The core pentapeptide sequence, TTNYT, consisting of amino acids 4-8 in peptide T, is the HIV envelope sequence required for attachment to the CD4 receptor. [NIH] Perception: The ability quickly and accurately to recognize similarities and differences among presented objects, whether these be pairs of words, pairs of number series, or multiple sets of these or other symbols such as geometric figures. [NIH] Percutaneous: Performed through the skin, as injection of radiopacque material in
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radiological examination, or the removal of tissue for biopsy accomplished by a needle. [EU] Perforation: 1. The act of boring or piercing through a part. 2. A hole made through a part or substance. [EU] Perfusion: Bathing an organ or tissue with a fluid. In regional perfusion, a specific area of the body (usually an arm or a leg) receives high doses of anticancer drugs through a blood vessel. Such a procedure is performed to treat cancer that has not spread. [NIH] Periaqueductal Gray: Central gray matter surrounding the cerebral aqueduct in the mesencephalon. Physiologically it is probably involved in rage reactions, the lordosis reflex, feeding responses, bladder tonus, and pain. [NIH] Pericarditis: Inflammation of the pericardium. [EU] Pericardium: The fibroserous sac surrounding the heart and the roots of the great vessels. [NIH]
Perilymph: The fluid contained within the space separating the membranous from the osseous labyrinth of the ear. [NIH] Perineal: Pertaining to the perineum. [EU] 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 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 Neuropathy: Nerve damage, usually affecting the feet and legs; causing pain, numbness, or a tingling feeling. Also called "somatic neuropathy" or "distal sensory polyneuropathy." [NIH] Peripheral Vascular Disease: Disease in the large blood vessels of the arms, legs, and feet. People who have had diabetes for a long time may get this because major blood vessels in their arms, legs, and feet are blocked and these limbs do not receive enough blood. The signs of PVD are aching pains in the arms, legs, and feet (especially when walking) and foot sores that heal slowly. Although people with diabetes cannot always avoid PVD, doctors say they have a better chance of avoiding it if they take good care of their feet, do not smoke, and keep both their blood pressure and diabetes under good control. [NIH] Peritoneal: Having to do with the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Peritoneal Cavity: The space enclosed by the peritoneum. It is divided into two portions, the greater sac and the lesser sac or omental bursa, which lies behind the stomach. The two sacs are connected by the foramen of Winslow, or epiploic foramen. [NIH] Peritoneal Dialysis: Dialysis fluid being introduced into and removed from the peritoneal cavity as either a continuous or an intermittent procedure. [NIH] Peritoneum: Endothelial lining of the abdominal cavity, the parietal peritoneum covering the inside of the abdominal wall and the visceral peritoneum covering the bowel, the mesentery, and certain of the organs. The portion that covers the bowel becomes the serosal layer of the bowel wall. [NIH] Peritonitis: Inflammation of the peritoneum; a condition marked by exudations in the
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peritoneum of serum, fibrin, cells, and pus. It is attended by abdominal pain and tenderness, constipation, vomiting, and moderate fever. [EU] Perivascular: Situated around a vessel. [EU] Peroneal Nerve: The lateral of the two terminal branches of the sciatic nerve. The peroneal (or fibular) nerve provides motor and sensory innervation to parts of the leg and foot. [NIH] Pertussis: An acute, highly contagious infection of the respiratory tract, most frequently affecting young children, usually caused by Bordetella pertussis; a similar illness has been associated with infection by B. parapertussis and B. bronchiseptica. It is characterized by a catarrhal stage, beginning after an incubation period of about two weeks, with slight fever, sneezing, running at the nose, and a dry cough. In a week or two the paroxysmal stage begins, with the characteristic paroxysmal cough, consisting of a deep inspiration, followed by a series of quick, short coughs, continuing until the air is expelled from the lungs; the close of the paroxysm is marked by a long-drawn, shrill, whooping inspiration, due to spasmodic closure of the glottis. This stage lasts three to four weeks, after which the convalescent stage begins, in which paroxysms grow less frequent and less violent, and finally cease. Called also whooping cough. [EU] PH: The symbol relating the hydrogen ion (H+) concentration or activity of a solution to that of a given standard solution. Numerically the pH is approximately equal to the negative logarithm of H+ concentration expressed in molarity. pH 7 is neutral; above it alkalinity increases and below it acidity increases. [EU] Phagocytosis: The engulfing of microorganisms, other cells, and foreign particles by phagocytic cells. [NIH] Pharmacodynamic: Is concerned with the response of living tissues to chemical stimuli, that is, the action of drugs on the living organism in the absence of disease. [NIH] Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] 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] Pharyngitis: Inflammation of the throat. [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] Phenoxybenzamine: An alpha-adrenergic anatagonist with long duration of action. It has been used to treat hypertension and as a peripheral vasodilator. [NIH] Phentolamine: A nonselective alpha-adrenergic antagonist. It is used in the treatment of hypertension and hypertensive emergencies, pheochromocytoma, vasospasm of Raynaud's disease and frostbite, clonidine withdrawal syndrome, impotence, and peripheral vascular disease. [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]
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Phenylephrine: An alpha-adrenergic agonist used as a mydriatic, nasal decongestant, and cardiotonic agent. [NIH] Phobia: A persistent, irrational, intense fear of a specific object, activity, or situation (the phobic stimulus), fear that is recognized as being excessive or unreasonable by the individual himself. When a phobia is a significant source of distress or interferes with social functioning, it is considered a mental disorder; phobic disorder (or neurosis). In DSM III phobic disorders are subclassified as agoraphobia, social phobias, and simple phobias. Used as a word termination denoting irrational fear of or aversion to the subject indicated by the stem to which it is affixed. [EU] Phobic Disorders: Anxiety disorders in which the essential feature is persistent and irrational fear of a specific object, activity, or situation that the individual feels compelled to avoid. The individual recognizes the fear as excessive or unreasonable. [NIH] Phosphodiesterase: Effector enzyme that regulates the levels of a second messenger, the cyclic GMP. [NIH] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] 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] Photocoagulation: Using a special strong beam of light (laser) to seal off bleeding blood vessels such as in the eye. The laser can also burn away blood vessels that should not have grown in the eye. This is the main treatment for diabetic retinopathy. [NIH] 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] Physostigmine: A cholinesterase inhibitor that is rapidly absorbed through membranes. It can be applied topically to the conjunctiva. It also can cross the blood-brain barrier and is used when central nervous system effects are desired, as in the treatment of severe anticholinergic toxicity. [NIH] Pigment: A substance that gives color to tissue. Pigments are responsible for the color of skin, eyes, and hair. [NIH] Piloerection: Involuntary erection or bristling of hairs. [NIH] Pilot study: The initial study examining a new method or treatment. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected
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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 expander: Artificial plasma extender. [EU] Plasma protein: One of the hundreds of different proteins present in blood plasma, including carrier proteins ( such albumin, transferrin, and haptoglobin), fibrinogen and other coagulation factors, complement components, immunoglobulins, enzyme inhibitors, precursors of substances such as angiotension and bradykinin, and many other types of proteins. [EU] Plasma Volume: Volume of plasma in the circulation. It is usually measured by indicator dilution techniques. [NIH] 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] Platelet Factor 4: A high-molecular-weight proteoglycan-platelet factor complex which is released from blood platelets by thrombin. It acts as a mediator in the heparin-neutralizing capacity of the blood and plays a role in platelet aggregation. At high ionic strength (I=0.75), the complex dissociates into the active component (molecular weight 29,000) and the proteoglycan carrier (chondroitin 4-sulfate, molecular weight 350,000). The molecule exists in the form of a dimer consisting of 8 moles of platelet factor 4 and 2 moles of proteoglycan. [NIH]
Platelet-Derived Growth Factor: Mitogenic peptide growth hormone carried in the alphagranules of platelets. It is released when platelets adhere to traumatized tissues. Connective tissue cells near the traumatized region respond by initiating the process of replication. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] 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
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for laboratory and industrial use. It occurs as a black powder (platinum black) and as a spongy substance (spongy platinum) and may have been known in Pliny's time as "alutiae". [NIH]
Plethysmograph: An instrument for measuring swelling or expansion of the body or part of it, such as a limb or digit, commonly used for the indirect measurement of blood flow or other displacement of internal fluids. [NIH] Plethysmography: Recording of change in the size of a part as modified by the circulation in it. [NIH] Plexus: A network or tangle; a general term for a network of lymphatic vessels, nerves, or veins. [EU] Pneumothorax: Accumulation of air or gas in the space between the lung and chest wall, resulting in partial or complete collapse of the lung. [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] Polyethylene: A vinyl polymer made from ethylene. It can be branched or linear. Branched or low-density polyethylene is tough and pliable but not to the same degree as linear polyethylene. Linear or high-density polyethylene has a greater hardness and tensile strength. Polyethylene is used in a variety of products, including implants and prostheses. [NIH]
Polymerase: An enzyme which catalyses the synthesis of DNA using a single DNA strand as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH] Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships. [NIH] Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] Polyradiculopathy: Disease or injury involving multiple spinal nerve roots. Polyradiculitis refers to inflammation of multiple spinal nerve roots. [NIH] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Polyuria: Urination of a large volume of urine with an increase in urinary frequency, commonly seen in diabetes. [NIH] Pons: The part of the central nervous system lying between the medulla oblongata and the mesencephalon, ventral to the cerebellum, and consisting of a pars dorsalis and a pars
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ventralis. [NIH] Popliteal: Compression of the nerve at the neck of the fibula. [NIH] Portal Vein: A short thick vein formed by union of the superior mesenteric vein and the splenic vein. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postmenopausal: Refers to the time after menopause. Menopause is the time in a woman's life when menstrual periods stop permanently; also called "change of life." [NIH] Postnatal: Occurring after birth, with reference to the newborn. [EU] Postoperative: After surgery. [NIH] Postprandial: Occurring after dinner, or after a meal; postcibal. [EU] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Post-synaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Post-translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Post-traumatic: Occurring as a result of or after injury. [EU] Postural: Pertaining to posture or position. [EU] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Potassium Channels: Cell membrane glycoproteins selective for potassium ions. [NIH] Potentiate: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Precipitating Factors: Factors associated with the definitive onset of a disease, illness, accident, behavioral response, or course of action. Usually one factor is more important or more obviously recognizable than others, if several are involved, and one may often be regarded as "necessary". Examples include exposure to specific disease; amount or level of an infectious organism, drug, or noxious agent, etc. [NIH] Preclinical: Before a disease becomes clinically recognizable. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Predisposition: A latent susceptibility to disease which may be activated under certain conditions, as by stress. [EU] Prednisolone: A glucocorticoid with the general properties of the corticosteroids. It is the drug of choice for all conditions in which routine systemic corticosteroid therapy is
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indicated, except adrenal deficiency states. [NIH] Prednisone: A synthetic anti-inflammatory glucocorticoid derived from cortisone. It is biologically inert and converted to prednisolone in the liver. [NIH] Preeclampsia: A toxaemia of late pregnancy characterized by hypertension, edema, and proteinuria, when convulsions and coma are associated, it is called eclampsia. [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] Pregnancy Outcome: Results of conception and ensuing pregnancy, including live birth, stillbirth, spontaneous abortion, induced abortion. The outcome may follow natural or artificial insemination or any of the various reproduction techniques, such as embryo transfer or fertilization in vitro. [NIH] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Pressoreceptors: Receptors in the vascular system, particularly the aorta and carotid sinus, which are sensitive to stretch of the vessel walls. [NIH] Presynaptic: Situated proximal to a synapse, or occurring before the synapse is crossed. [EU] Presynaptic Terminals: The distal terminations of axons which are specialized for the release of neurotransmitters. Also included are varicosities along the course of axons which have similar specializations and also release transmitters. Presynaptic terminals in both the central and peripheral nervous systems are included. [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] Priapism: Persistent abnormal erection of the penis, usually without sexual desire, and accompanied by pain and tenderness. It is seen in diseases and injuries of the spinal cord, and may be caused by vesical calculus and certain injuries to the penis. [EU] 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] Proctocolitis: Inflammation of the rectum and colon. [NIH] Progesterone: Pregn-4-ene-3,20-dione. The principal progestational hormone of the body, secreted by the corpus luteum, adrenal cortex, and placenta. Its chief function is to prepare the uterus for the reception and development of the fertilized ovum. It acts as an antiovulatory agent when administered on days 5-25 of the menstrual cycle. [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Prone: Having the front portion of the body downwards. [NIH] Prone Position: The posture of an individual lying face down. [NIH] Pro-Opiomelanocortin: A precursor protein, MW 30,000, synthesized mainly in the anterior pituitary gland but also found in the hypothalamus, brain, and several peripheral tissues. It incorporates the amino acid sequences of ACTH and beta-lipotropin. These two hormones,
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in turn, contain the biologically active peptides MSH, corticotropin-like intermediate lobe peptide, alpha-lipotropin, endorphins, and methionine enkephalin. [NIH] Prophase: The first phase of cell division, in which the chromosomes become visible, the nucleus starts to lose its identity, the spindle appears, and the centrioles migrate toward opposite poles. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Proportional: Being in proportion : corresponding in size, degree, or intensity, having the same or a constant ratio; of, relating to, or used in determining proportions. [EU] Prospective Studies: Observation of a population for a sufficient number of persons over a sufficient number of years to generate incidence or mortality rates subsequent to the selection of the study group. [NIH] Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] Prostaglandin: Any of a group of components derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway that are extremely potent mediators of a diverse group of physiologic processes. The abbreviation for prostaglandin is PG; specific compounds are designated by adding one of the letters A through I to indicate the type of substituents found on the hydrocarbon skeleton and a subscript (1, 2 or 3) to indicate the number of double bonds in the hydrocarbon skeleton e.g., PGE2. The predominant naturally occurring prostaglandins all have two double bonds and are synthesized from arachidonic acid (5,8,11,14-eicosatetraenoic acid) by the pathway shown in 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] Prostaglandin-Endoperoxide Synthase: An enzyme complex that catalyzes the formation of prostaglandins from the appropriate unsaturated fatty acid, molecular oxygen, and a reduced acceptor. EC 1.14.99.1. [NIH] Prostaglandins A: (13E,15S)-15-Hydroxy-9-oxoprosta-10,13-dien-1-oic acid (PGA(1)); (5Z,13E,15S)-15-hydroxy-9-oxoprosta-5,10,13-trien-1-oic acid (PGA(2)); (5Z,13E,15S,17Z)-15hydroxy-9-oxoprosta-5,10,13,17-tetraen-1-oic acid (PGA(3)). A group of naturally occurring secondary prostaglandins derived from PGE. PGA(1) and PGA(2) as well as their 19hydroxy derivatives are found in many organs and tissues. [NIH] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Prostate gland: A gland in the male reproductive system just below the bladder. It surrounds part of the urethra, the canal that empties the bladder, and produces a fluid that forms part of semen. [NIH]
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Prostatectomy: Complete or partial surgical removal of the prostate. Three primary approaches are commonly employed: suprapubic - removal through an incision above the pubis and through the urinary bladder; retropubic - as for suprapubic but without entering the urinary bladder; and transurethral (transurethral resection of prostate). [NIH] Prostatic Hyperplasia: Enlargement or overgrowth of the prostate gland as a result of an increase in the number of its constituent cells. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protective Agents: Synthetic or natural substances which are given to prevent a disease or disorder or are used in the process of treating a disease or injury due to a poisonous agent. [NIH]
Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific proteinbinding measures are often used as assays in diagnostic assessments. [NIH] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein 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 Kinases: A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein. EC 2.7.1.37. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Proteinuria: The presence of protein in the urine, indicating that the kidneys are not working properly. [NIH] Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Prothrombin: A plasma protein that is the inactive precursor of thrombin. It is converted to thrombin by a prothrombin activator complex consisting of factor Xa, factor V, phospholipid, and calcium ions. Deficiency of prothrombin leads to hypoprothrombinemia. [NIH]
Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Proto-Oncogene Proteins: Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity. [NIH] Proto-Oncogene Proteins c-mos: Cellular proteins encoded by the c-mos genes. They
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function in the cell cycle to maintain maturation promoting factor in the active state and have protein-serine/threonine kinase activity. Oncogenic transformation can take place when c-mos proteins are expressed at the wrong time. [NIH] Protozoa: A subkingdom consisting of unicellular organisms that are the simplest in the animal kingdom. Most are free living. They range in size from submicroscopic to macroscopic. Protozoa are divided into seven phyla: Sarcomastigophora, Labyrinthomorpha, Apicomplexa, Microspora, Ascetospora, Myxozoa, and Ciliophora. [NIH] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Pruritic: Pertaining to or characterized by pruritus. [EU] Pruritus: An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. [NIH] Psoriasis: A common genetically determined, chronic, inflammatory skin disease characterized by rounded erythematous, dry, scaling patches. The lesions have a predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region. Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in psoriasis. [NIH] Psychiatric: Pertaining to or within the purview of psychiatry. [EU] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Psychogenic: Produced or caused by psychic or mental factors rather than organic factors. [EU]
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] Ptosis: 1. Prolapse of an organ or part. 2. Drooping of the upper eyelid from paralysis of the third nerve or from sympathetic innervation. [EU] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]
Pulmonary: Relating to the lungs. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] Pulmonary Edema: An accumulation of an excessive amount of watery fluid in the lungs, may be caused by acute exposure to dangerous concentrations of irritant gasses. [NIH] Pulmonary Embolism: Embolism in the pulmonary artery or one of its branches. [NIH] Pulmonary hypertension: Abnormally high blood pressure in the arteries of the lungs. [NIH] Pulmonary Ventilation: The total volume of gas per minute inspired or expired measured in liters per minute. [NIH]
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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] Purifying: Respiratory equipment whose function is to remove contaminants from otherwise wholesome air. [NIH] Purines: A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include adenine and guanine, constituents of nucleic acids, as well as many alkaloids such as caffeine and theophylline. Uric acid is the metabolic end product of purine metabolism. [NIH] Putrefaction: The process of decomposition of animal and vegetable matter by living organisms. [NIH] Pyrogenic: Inducing fever. [EU] Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] Radial Artery: The direct continuation of the brachial trunk, originating at the bifurcation of the brachial artery opposite the neck of the radius. Its branches may be divided into three groups corresponding to the three regions in which the vessel is situated, the forearm, wrist, and hand. [NIH] Radial Nerve: A major nerve of the upper extremity. In humans the fibers of the radial nerve originate in the lower cervical and upper thoracic spinal cord (usually C5 to T1), travel via the posterior cord of the brachial plexus, and supply motor innervation to extensor muscles of the arm and cutaneous sensory fibers to extensor regions of the arm and hand. [NIH]
Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH] Radical prostatectomy: Surgery to remove the entire prostate. The two types of radical prostatectomy are retropubic prostatectomy and perineal prostatectomy. [NIH] Radicular: Having the character of or relating to a radicle or root. [NIH] Radiculopathy: Disease involving a spinal nerve root (see spinal nerve roots) which may result from compression related to intervertebral disk displacement; spinal cord injuries; spinal diseases; and other conditions. Clinical manifestations include radicular pain, weakness, and sensory loss referable to structures innervated by the involved nerve root. [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
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proteins (e.g., bovine gamma-globulin or human serum albumin) capable of inducing antibody formation. [NIH] Radioimmunotherapy: Radiotherapy where cytotoxic radionuclides are linked to antibodies in order to deliver toxins directly to tumor targets. Therapy with targeted radiation rather than antibody-targeted toxins (immunotoxins) has the advantage that adjacent tumor cells, which lack the appropriate antigenic determinants, can be destroyed by radiation cross-fire. Radioimmunotherapy is sometimes called targeted radiotherapy, but this latter term can also refer to radionuclides linked to non-immune molecules (radiotherapy). [NIH] Radioisotope: An unstable element that releases radiation as it breaks down. Radioisotopes can be used in imaging tests or as a treatment for cancer. [NIH] Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH] Radiological: Pertaining to radiodiagnostic and radiotherapeutic procedures, and interventional radiology or other planning and guiding medical radiology. [NIH] Radiopharmaceuticals: Drugs containing a radioactive substance that are used in the diagnosis and treatment of cancer and in pain management of bone metastases. Also called radioactive drugs. [NIH] Radiotherapy: The use of ionizing radiation to treat malignant neoplasms and other benign conditions. The most common forms of ionizing radiation used as therapy are x-rays, gamma rays, and electrons. A special form of radiotherapy, targeted radiotherapy, links a cytotoxic radionuclide to a molecule that targets the tumor. When this molecule is an antibody or other immunologic molecule, the technique is called radioimmunotherapy. [NIH] Radius: The lateral bone of the forearm. [NIH] Rage: Fury; violent, intense anger. [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] 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] 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] Rectal: By or having to do with the rectum. The rectum is the last 8 to 10 inches of the large intestine and ends at the anus. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Red blood cells: RBCs. Cells that carry oxygen to all parts of the body. Also called erythrocytes. [NIH] Red Nucleus: A pinkish-yellow portion of the midbrain situated in the rostral
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mesencephalic tegmentum. It receives a large projection from the contralateral half of the cerebellum via the superior cerebellar peduncle and a projection from the ipsilateral motor cortex. [NIH] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] 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] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Refractory: Not readily yielding to treatment. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Relapse: The return of signs and symptoms of cancer after a period of improvement. [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 Dialysis: Removal of certain elements from the blood based on the difference in their rates of diffusion through a semipermeable membrane. [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] 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] Renovascular: Of or pertaining to the blood vessels of the kidneys. [EU] 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] Reproduction Techniques: Methods pertaining to the generation of new individuals. [NIH] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into
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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] Respiratory Burst: A large increase in oxygen uptake by neutrophils and most types of tissue macrophages through activation of an NADPH-cytochrome b-dependent oxidase that reduces oxygen to a superoxide. Individuals with an inherited defect in which the oxidase that reduces oxygen to superoxide is decreased or absent (granulomatous disease, chronic) often die as a result of recurrent bacterial infections. [NIH] Respiratory System: The tubular and cavernous organs and structures, by means of which pulmonary ventilation and gas exchange between ambient air and the blood are brought about. [NIH] Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [NIH] Resuscitation: The restoration to life or consciousness of one apparently dead; it includes such measures as artificial respiration and cardiac massage. [EU] Reticular: Coarse-fibered, netlike dermis layer. [NIH] Reticular Formation: A region extending from the pons & medulla oblongata through the mesencephalon, characterized by a diversity of neurons of various sizes and shapes, arranged in different aggregations and enmeshed in a complicated fiber network. [NIH] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] Retinal: 1. Pertaining to the retina. 2. The aldehyde of retinol, derived by the oxidative enzymatic splitting of absorbed dietary carotene, and having vitamin A activity. In the retina, retinal combines with opsins to form visual pigments. One isomer, 11-cis retinal combines with opsin in the rods (scotopsin) to form rhodopsin, or visual purple. Another, all-trans retinal (trans-r.); visual yellow; xanthopsin) results from the bleaching of rhodopsin by light, in which the 11-cis form is converted to the all-trans form. Retinal also combines with opsins in the cones (photopsins) to form the three pigments responsible for colour vision. Called also retinal, and retinene1. [EU] Retinal Ganglion Cells: Cells of the innermost nuclear layer of the retina, the ganglion cell layer, which project axons through the optic nerve to the brain. They are quite variable in size and in the shapes of their dendritic arbors, which are generally confined to the inner plexiform layer. [NIH] Retinoblastoma: An eye cancer that most often occurs in children younger than 5 years. It occurs in hereditary and nonhereditary (sporadic) forms. [NIH] Retinol: Vitamin A. It is essential for proper vision and healthy skin and mucous membranes. Retinol is being studied for cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Retinopathy: 1. Retinitis (= inflammation of the retina). 2. Retinosis (= degenerative, noninflammatory condition of the retina). [EU] Retrograde: 1. Moving backward or against the usual direction of flow. 2. Degenerating, deteriorating, or catabolic. [EU] Retropubic: A potential space between the urinary bladder and the symphisis and body of the pubis. [NIH]
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Retropubic prostatectomy: Surgery to remove the prostate through an incision made in the abdominal wall. [NIH] Rheology: The study of the deformation and flow of matter, usually liquids or fluids, and of the plastic flow of solids. The concept covers consistency, dilatancy, liquefaction, resistance to flow, shearing, thixotrophy, and viscosity. [NIH] Rheumatism: A group of disorders marked by inflammation or pain in the connective tissue structures of the body. These structures include bone, cartilage, and fat. [NIH] Rheumatoid: Resembling rheumatism. [EU] Rheumatoid arthritis: A form of arthritis, the cause of which is unknown, although infection, hypersensitivity, hormone imbalance and psychologic stress have been suggested as possible causes. [NIH] Rhinitis: Inflammation of the mucous membrane of the nose. [NIH] Rhombencephalon: That part of the brain stem constituting the medulla oblongata (myelencephalon) and pons (metencephalon). [NIH] Ribonuclease: RNA-digesting enzyme. [NIH] Ribose: A pentose active in biological systems usually in its D-form. [NIH] Rickettsiae: One of a group of obligate intracellular parasitic microorganisms, once regarded as intermediate in their properties between bacteria and viruses but now classified as bacteria in the order Rickettsiales, which includes 17 genera and 3 families: Rickettsiace. [NIH]
Rigidity: Stiffness or inflexibility, chiefly that which is abnormal or morbid; rigor. [EU] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Rod: A reception for vision, located in the retina. [NIH] Saline: A solution of salt and water. [NIH] Saliva: The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptylin. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Salvage Therapy: A therapeutic approach, involving chemotherapy, radiation therapy, or surgery, after initial regimens have failed to lead to improvement in a patient's condition. Salvage therapy is most often used for neoplastic diseases. [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] Saponins: Sapogenin glycosides. A type of glycoside widely distributed in plants. Each consists of a sapogenin as the aglycon moiety, and a sugar. The sapogenin may be a steroid or a triterpene and the sugar may be glucose, galactose, a pentose, or a methylpentose. Sapogenins are poisonous towards the lower forms of life and are powerful hemolytics when injected into the blood stream able to dissolve red blood cells at even extreme dilutions. [NIH] Scarlet Fever: Infection with group A streptococci that is characterized by tonsillitis and pharyngitis. An erythematous rash is commonly present. [NIH] Schizoid: Having qualities resembling those found in greater degree in schizophrenics; a person of schizoid personality. [NIH]
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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] Sciatic Nerve: A nerve which originates in the lumbar and sacral spinal cord (L4 to S3) and supplies motor and sensory innervation to the lower extremity. The sciatic nerve, which is the main continuation of the sacral plexus, is the largest nerve in the body. It has two major branches, the tibial nerve and the peroneal nerve. [NIH] Scleroderma: A chronic disorder marked by hardening and thickening of the skin. Scleroderma can be localized or it can affect the entire body (systemic). [NIH] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Scoliosis: A lateral curvature of the spine. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Second Messenger Systems: Systems in which an intracellular signal is generated in response to an intercellular primary messenger such as a hormone or neurotransmitter. They are intermediate signals in cellular processes such as metabolism, secretion, contraction, phototransduction, and cell growth. Examples of second messenger systems are the adenyl cyclase-cyclic AMP system, the phosphatidylinositol diphosphate-inositol triphosphate system, and the cyclic GMP system. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Sedative: 1. Allaying activity and excitement. 2. An agent that allays excitement. [EU] Sedentary: 1. Sitting habitually; of inactive habits. 2. Pertaining to a sitting posture. [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] Selection Bias: The introduction of error due to systematic differences in the characteristics between those selected and those not selected for a given study. In sampling bias, error is the result of failure to ensure that all members of the reference population have a known chance of selection in the sample. [NIH] Sella: A deep depression in the shape of a Turkish saddle in the upper surface of the body of the sphenoid bone in the deepest part of which is lodged the hypophysis cerebri. [NIH] Semen: The thick, yellowish-white, viscid fluid secretion of male reproductive organs discharged upon ejaculation. In addition to reproductive organ secretions, it contains spermatozoa and their nutrient plasma. [NIH] Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU]
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Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [NIH] Sensibility: The ability to receive, feel and appreciate sensations and impressions; the quality of being sensitive; the extend to which a method gives results that are free from false negatives. [NIH] 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] Sensory loss: A disease of the nerves whereby the myelin or insulating sheath of myelin on the nerves does not stay intact and the messages from the brain to the muscles through the nerves are not carried properly. [NIH] Sepsis: The presence of bacteria in the bloodstream. [NIH] Septic: Produced by or due to decomposition by microorganisms; putrefactive. [EU] Septicemia: Systemic disease associated with the presence and persistence of pathogenic microorganisms or their toxins in the blood. Called also blood poisoning. [EU] Sequence Analysis: A multistage process that includes the determination of a sequence (protein, carbohydrate, etc.), its fragmentation and analysis, and the interpretation of the resulting sequence information. [NIH] Sequence Homology: The degree of similarity between sequences. Studies of amino acid and nucleotide sequences provide useful information about the genetic relatedness of certain species. [NIH] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from glycine or threonine. It is involved in the biosynthesis of purines, pyrimidines, and other amino acids. [NIH] Serologic: Analysis of a person's serum, especially specific immune or lytic serums. [NIH] 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] Serotonin Uptake Inhibitors: Compounds that specifically inhibit the reuptake of serotonin in the brain. This increases the serotonin concentration in the synaptic cleft which then activates serotonin receptors to a greater extent. These agents have been used in treatment of depression, panic disorder, obsessive-compulsive behavior, and alcoholism, as analgesics, and to treat obesity and bulimia. Many of the adrenergic uptake inhibitors also inhibit serotonin uptake; they are not included here. [NIH] Serous: Having to do with serum, the clear liquid part of blood. [NIH] Serrata: The serrated anterior border of the retina located approximately 8.5 mm from the limbus and adjacent to the pars plana of the ciliary body. [NIH] Sertraline: A selective serotonin uptake inhibitor that is used in the treatment of depression. [NIH]
Sertraline Hydrochloride: Selective serotonin uptake inhibitor. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH]
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Serum Albumin: A major plasma protein that serves in maintaining the plasma colloidal osmotic pressure and transporting large organic anions. [NIH] Sex Characteristics: Those characteristics that distinguish one sex from the other. The primary sex characteristics are the ovaries and testes and their related hormones. Secondary sex characteristics are those which are masculine or feminine but not directly related to reproduction. [NIH] Sex Determination: The biological characteristics which distinguish human beings as female or male. [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] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Sleep apnea: A serious, potentially life-threatening breathing disorder characterized by repeated cessation of breathing due to either collapse of the upper airway during sleep or absence of respiratory effort. [NIH] Small cell lung cancer: A type of lung cancer in which the cells appear small and round when viewed under the microscope. Also called oat cell lung cancer. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]
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Sneezing: Sudden, forceful, involuntary expulsion of air from the nose and mouth caused by irritation to the mucous membranes of the upper respiratory tract. [NIH] Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Social Isolation: The separation of individuals or groups resulting in the lack of or minimizing of social contact and/or communication. This separation may be accomplished by physical separation, by social barriers and by psychological mechanisms. In the latter, there may be interaction but no real communication. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Sodium Nitrite: Nitrous acid sodium salt. Used in many industrial processes, in meat curing, coloring, and preserving, and as a reagent in analytical chemistry. It is used therapeutically as an antidote in cyanide poisoning. The compound is toxic and mutagenic and will react in vivo with secondary or tertiary amines thereby producing highly carcinogenic nitrosamines. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solid tumor: Cancer of body tissues other than blood, bone marrow, or the lymphatic system. [NIH] Solitary Nucleus: Gray matter located in the dorsomedial part of the medulla oblongata associated with the solitary tract. The solitary nucleus receives inputs from most organ systems including the terminations of the facial, glossopharyngeal, and vagus nerves. It is a major coordinator of autonomic nervous system regulation of cardiovascular, respiratory, gustatory, gastrointestinal, and chemoreceptive aspects of homeostasis. The solitary nucleus is also notable for the large number of neurotransmitters which are found therein. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] Soma: The body as distinct from the mind; all the body tissue except the germ cells; all the axial body. [NIH] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Somatic cells: All the body cells except the reproductive (germ) cells. [NIH] 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 alterations. [NIH] Space Flight: Travel beyond the earth's atmosphere. [NIH] Spasm: An involuntary contraction of a muscle or group of muscles. Spasms may involve skeletal muscle or smooth muscle. [NIH]
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Spasmodic: Of the nature of a spasm. [EU] Spasmogenic: Capable of producing convulsions. [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] Spasticity: A state of hypertonicity, or increase over the normal tone of a muscle, with heightened deep tendon reflexes. [EU] Spatial disorientation: Loss of orientation in space where person does not know which way is up. [NIH] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] 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] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spinal Cord Injuries: Penetrating and non-penetrating injuries to the spinal cord resulting from traumatic external forces (e.g., wounds, gunshot; whiplash injuries; etc.). [NIH] Spinal Nerve Roots: The paired bundles of nerve fibers entering and leaving the spinal cord at each segment. The dorsal and ventral nerve roots join to form the mixed segmental spinal nerves. The dorsal roots are generally afferent, formed by the central projections of the spinal (dorsal root) ganglia sensory cells, and the ventral roots efferent, comprising the axons of spinal motor and autonomic preganglionic neurons. There are, however, some exceptions to this afferent/efferent rule. [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] Splenic Vein: Vein formed by the union (at the hilus of the spleen) of several small veins from the stomach, pancreas, spleen and mesentery. [NIH] Spontaneous Abortion: The non-induced birth of an embryo or of fetus prior to the stage of viability at about 20 weeks of gestation. [NIH] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU]
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Spores: The reproductive elements of lower organisms, such as protozoa, fungi, and cryptogamic plants. [NIH] Sprains and Strains: A collective term for muscle and ligament injuries without dislocation or fracture. A sprain is a joint injury in which some of the fibers of a supporting ligament are ruptured but the continuity of the ligament remains intact. A strain is an overstretching or overexertion of some part of the musculature. [NIH] Squamous: Scaly, or platelike. [EU] Squamous cell carcinoma: Cancer that begins in squamous cells, which are thin, flat cells resembling fish scales. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. Also called epidermoid carcinoma. [NIH] Squamous cell carcinoma: Cancer that begins in squamous cells, which are thin, flat cells resembling fish scales. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. Also called epidermoid carcinoma. [NIH] Stabilization: The creation of a stable state. [EU] 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] Steady state: Dynamic equilibrium. [EU] Steel: A tough, malleable, iron-based alloy containing up to, but no more than, two percent carbon and often other metals. It is used in medicine and dentistry in implants and instrumentation. [NIH] Stellate: Star shaped. [NIH] Stellate Ganglion: A paravertebral sympathetic ganglion formed by the fusion of the inferior cervical and first thoracic ganglia. [NIH] Stem Cells: Relatively undifferentiated cells of the same lineage (family type) that retain the ability to divide and cycle throughout postnatal life to provide cells that can become specialized and take the place of those that die or are lost. [NIH] Stent: A device placed in a body structure (such as a blood vessel or the gastrointestinal tract) to provide support and keep the structure open. [NIH] 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] Stillbirth: The birth of a dead fetus or baby. [NIH] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]
Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH]
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Stomach Ulcer: An open sore in the lining of the stomach. Also called gastric ulcer. [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] Streptococcal: Caused by infection due to any species of streptococcus. [NIH] Streptococci: A genus of spherical Gram-positive bacteria occurring in chains or pairs. They are widely distributed in nature, being important pathogens but often found as normal commensals in the mouth, skin, and intestine of humans and other animals. [NIH] Streptococcus: A genus of gram-positive, coccoid bacteria whose organisms occur in pairs or chains. No endospores are produced. Many species exist as commensals or parasites on man or animals with some being highly pathogenic. A few species are saprophytes and occur in the natural environment. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Stroke Volume: The amount of blood pumped out of the heart per beat not to be confused with cardiac output (volume/time). [NIH] Stroma: The middle, thickest layer of tissue in the cornea. [NIH] Stupor: Partial or nearly complete unconsciousness, manifested by the subject's responding only to vigorous stimulation. Also, in psychiatry, a disorder marked by reduced responsiveness. [EU] Subacute: Somewhat acute; between acute and chronic. [EU] Subarachnoid: Situated or occurring between the arachnoid and the pia mater. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subcutaneous: Beneath the skin. [NIH] Subdural Effusion: Leakage and accumulation of cerebrospinal fluid in the subdural space which may be associated with an infectious process; craniocerebral trauma; brain neoplasms; intracranial hypotension; and other conditions. [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] Suction: The removal of secretions, gas or fluid from hollow or tubular organs or cavities by means of a tube and a device that acts on negative pressure. [NIH] Sudden cardiac death: Cardiac arrest caused by an irregular heartbeat. [NIH] Sudden death: Cardiac arrest caused by an irregular heartbeat. The term "death" is somewhat misleading, because some patients survive. [NIH]
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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] Sulfuric acid: A strong acid that, when concentrated is extemely corrosive to the skin and mucous membranes. It is used in making fertilizers, dyes, electroplating, and industrial explosives. [NIH] Superantigens: Microbial antigens that have in common an extremely potent activating effect on T-cells that bear a specific variable region. Superantigens cross-link the variable region with class II MHC proteins regardless of the peptide binding in the T-cell receptor's pocket. The result is a transient expansion and subsequent death and anergy of the T-cells with the appropriate variable regions. [NIH] Superoxide: Derivative of molecular oxygen that can damage cells. [NIH] Superoxide Dismutase: An oxidoreductase that catalyzes the reaction between superoxide anions and hydrogen to yield molecular oxygen and hydrogen peroxide. The enzyme protects the cell against dangerous levels of superoxide. EC 1.15.1.1. [NIH] Supine: Having the front portion of the body upwards. [NIH] Supine Position: The posture of an individual lying face up. [NIH] Supplementation: Adding nutrients to the diet. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Supraspinal: Above the spinal column or any spine. [NIH] 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] Suspensions: Colloids with liquid continuous phase and solid dispersed phase; the term is used loosely also for solid-in-gas (aerosol) and other colloidal systems; water-insoluble drugs may be given as suspensions. [NIH] Sweat: The fluid excreted by the sweat glands. It consists of water containing sodium chloride, phosphate, urea, ammonia, and other waste products. [NIH] Sweat Glands: Sweat-producing structures that are embedded in the dermis. Each gland consists of a single tube, a coiled body, and a superficial duct. [NIH] Sympathetic Nervous System: The thoracolumbar division of the autonomic nervous system. Sympathetic preganglionic fibers originate in neurons of the intermediolateral column of the spinal cord and project to the paravertebral and prevertebral ganglia, which in turn project to target organs. The sympathetic nervous system mediates the body's response to stressful situations, i.e., the fight or flight reactions. It often acts reciprocally to the parasympathetic system. [NIH] Sympatholytics: Drugs that inhibit the actions of the sympathetic nervous system by any mechanism. The most common of these are the adrenergic antagonists and drugs that deplete norepinephrine or reduce the release of transmitters from adrenergic postganglionic terminals. Drugs that act in the central nervous system to reduce sympathetic activity (e.g., centrally acting alpha-2 adrenergic agonists) are included here. [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
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nervous system. Called also adrenergic. [EU] Symphysis: A secondary cartilaginous joint. [NIH] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Synapses: Specialized junctions at which a neuron communicates with a target cell. At classical synapses, a neuron's presynaptic terminal releases a chemical transmitter stored in synaptic vesicles which diffuses across a narrow synaptic cleft and activates receptors on the postsynaptic membrane of the target cell. The target may be a dendrite, cell body, or axon of another neuron, or a specialized region of a muscle or secretory cell. Neurons may also communicate through direct electrical connections which are sometimes called electrical synapses; these are not included here but rather in gap junctions. [NIH] Synapsis: The pairing between homologous chromosomes of maternal and paternal origin during the prophase of meiosis, leading to the formation of gametes. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Syncope: A temporary suspension of consciousness due to generalized cerebral schemia, a faint or swoon. [EU] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Systemic: Affecting the entire body. [NIH] Systemic lupus erythematosus: SLE. A chronic inflammatory connective tissue disease marked by skin rashes, joint pain and swelling, inflammation of the kidneys, inflammation of the fibrous tissue surrounding the heart (i.e., the pericardium), as well as other problems. Not all affected individuals display all of these problems. May be referred to as lupus. [NIH] 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 contracts and blood begins to flow. [NIH] Tachycardia: Excessive rapidity in the action of the heart, usually with a heart rate above 100 beats per minute. [NIH] Tachypnea: Rapid breathing. [NIH] Tacrine: A cholinesterase inhibitor that crosses the blood-brain barrier. Tacrine has been used to counter the effects of muscle relaxants, as a respiratory stimulant, and in the treatment of Alzheimer's disease and other central nervous system disorders. [NIH] Teichoic Acids: Bacterial polysaccharides that are rich in phosphodiester linkages. They are the major components of the cell walls and membranes of many bacteria. [NIH] Telangiectasia: The permanent enlargement of blood vessels, causing redness in the skin or mucous membranes. [NIH] Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the skull, and containing the organs of hearing. [NIH] Terbutaline: A selective beta-2 adrenergic agonist used as a bronchodilator and tocolytic. [NIH]
Testicular: Pertaining to a testis. [EU] Testis: Either of the paired male reproductive glands that produce the male germ cells and
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the male hormones. [NIH] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] Tetani: Causal agent of tetanus. [NIH] Tetanic: Having the characteristics of, or relating to tetanus. [NIH] Tetanus: A disease caused by tetanospasmin, a powerful protein toxin produced by Clostridium tetani. Tetanus usually occurs after an acute injury, such as a puncture wound or laceration. Generalized tetanus, the most common form, is characterized by tetanic muscular contractions and hyperreflexia. Localized tetanus presents itself as a mild condition with manifestations restricted to muscles near the wound. It may progress to the generalized form. [NIH] Thalamic: Cell that reaches the lateral nucleus of amygdala. [NIH] Thalamic Diseases: Disorders of the centrally located thalamus, which integrates a wide range of cortical and subcortical information. Manifestations include sensory loss, movement disorders; ataxia, pain syndromes, visual disorders, a variety of neuropsychological conditions, and coma. Relatively common etiologies include cerebrovascular disorders; craniocerebral trauma; brain neoplasms; brain hypoxia; intracranial hemorrhages; and infectious processes. [NIH] 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] Third Ventricle: A narrow cleft inferior to the corpus callosum, within the diencephalon, between the paired thalami. Its floor is formed by the hypothalamus, its anterior wall by the lamina terminalis, and its roof by ependyma. It communicates with the fourth ventricle by the cerebral aqueduct, and with the lateral ventricles by the interventricular foramina. [NIH] Thoracic: Having to do with the chest. [NIH] Thoracotomy: Surgical incision into the chest wall. [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] Thrombocytopenia: A decrease in the number of blood platelets. [NIH] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]
Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thromboxanes: Physiologically active compounds found in many organs of the body. They are formed in vivo from the prostaglandin endoperoxides and cause platelet aggregation, contraction of arteries, and other biological effects. Thromboxanes are important mediators of the actions of polyunsaturated fatty acids transformed by cyclooxygenase. [NIH] Thrombus: An aggregation of blood factors, primarily platelets and fibrin with entrapment
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of cellular elements, frequently causing vascular obstruction at the point of its formation. Some authorities thus differentiate thrombus formation from simple coagulation or clot formation. [EU] Thymus: An organ that is part of the lymphatic system, in which T lymphocytes grow and multiply. The thymus is in the chest behind the breastbone. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Thyroid Gland: A highly vascular endocrine gland consisting of two lobes, one on either side of the trachea, joined by a narrow isthmus; it produces the thyroid hormones which are concerned in regulating the metabolic rate of the body. [NIH] Thyroid Hormones: Hormones secreted by the thyroid gland. [NIH] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH] Tibial Nerve: The medial terminal branch of the sciatic nerve. The tibial nerve fibers originate in lumbar and sacral spinal segments (L4 to S2). They supply motor and sensory innervation to parts of the calf and foot. [NIH] Tick-Borne Diseases: Bacterial, viral, or parasitic diseases transmitted to humans and animals by the bite of infected ticks. The families Ixodidae and Argasidae contain many bloodsucking species that are important pests of man and domestic birds and mammals and probably exceed all other arthropods in the number and variety of disease agents they transmit. Many of the tick-borne diseases are zoonotic. [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] Tinnitus: Sounds that are perceived in the absence of any external noise source which may take the form of buzzing, ringing, clicking, pulsations, and other noises. Objective tinnitus refers to noises generated from within the ear or adjacent structures that can be heard by other individuals. The term subjective tinnitus is used when the sound is audible only to the affected individual. Tinnitus may occur as a manifestation of cochlear diseases; vestibulocochlear nerve diseases; intracranial hypertension; craniocerebral trauma; and other conditions. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tissue Distribution: Accumulation of a drug or chemical substance in various organs (including those not relevant to its pharmacologic or therapeutic action). This distribution depends on the blood flow or perfusion rate of the organ, the ability of the drug to penetrate organ membranes, tissue specificity, protein binding. The distribution is usually expressed as tissue to plasma ratios. [NIH] Tissue Survival: The span of viability of a tissue or an organ. [NIH] Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU] Tomography: Imaging methods that result in sharp images of objects located on a chosen plane and blurred images located above or below the plane. [NIH] Tonicity: The normal state of muscular tension. [NIH]
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Tonsillitis: Inflammation of the tonsils, especially the palatine tonsils. It is often caused by a bacterium. Tonsillitis may be acute, chronic, or recurrent. [NIH] Tonus: A state of slight tension usually present in muscles even when they are not undergoing active contraction. [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] Topoisomerase inhibitors: A family of anticancer drugs. The topoisomerase enzymes are responsible for the arrangement and rearrangement of DNA in the cell and for cell growth and replication. Inhibiting these enzymes may kill cancer cells or stop their growth. [NIH] Torsion: A twisting or rotation of a bodily part or member on its axis. [NIH] Tourniquet: A device, band or elastic tube applied temporarily to press upon an artery to stop bleeding; a device to compress a blood vessel in order to stop bleeding. [NIH] Toxaemia: 1. The condition resulting from the spread of bacterial products (toxins) by the bloodstream. 2. A condition resulting from metabolic disturbances, e.g. toxaemia of pregnancy. [EU] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicokinetics: Study of the absorption, distribution, metabolism, and excretion of test substances. [NIH] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [NIH] Toxoid: The material resulting from the treatment of toxin in such a way that the toxic properties are inactivated whilst the antigenic potency remains intact. [NIH] Trabecular Meshwork: A porelike structure surrounding the entire circumference of the anterior chamber through which aqueous humor circulates to the canal of Schlemm. [NIH] Trabeculectomy: Any surgical procedure for treatment of glaucoma by means of puncture or reshaping of the trabecular meshwork. It includes goniotomy, trabeculotomy, and laser perforation. [NIH] Trace element: Substance or element essential to plant or animal life, but present in extremely small amounts. [NIH] Tracer: A substance (such as a radioisotope) used in imaging procedures. [NIH] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Traction: The act of pulling. [NIH] Tractus: A part of some structure, usually that part along which something passes. [NIH] Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. [NIH] Transcutaneous: Transdermal. [EU]
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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] Transfer Factor: Factor derived from leukocyte lysates of immune donors which can transfer both local and systemic cellular immunity to nonimmune recipients. [NIH] Transfusion: The infusion of components of blood or whole blood into the bloodstream. The blood may be donated from another person, or it may have been taken from the person earlier and stored until needed. [NIH] 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] Tremor: Cyclical movement of a body part that can represent either a physiologic process or a manifestation of disease. Intention or action tremor, a common manifestation of cerebellar diseases, is aggravated by movement. In contrast, resting tremor is maximal when there is no attempt at voluntary movement, and occurs as a relatively frequent manifestation of Parkinson disease. [NIH] Tricuspid Atresia: Absence of the orifice between the right atrium and ventricle, with the presence of an atrial defect through which all the systemic venous return reaches the left heart. As a result, there is left ventricular hypertrophy because the right ventricle is absent or not functional. [NIH] Trigeminal: Cranial nerve V. It is sensory for the eyeball, the conjunctiva, the eyebrow, the skin of face and scalp, the teeth, the mucous membranes in the mouth and nose, and is motor to the muscles of mastication. [NIH] Trophic: Of or pertaining to nutrition. [EU] 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] Tuberous Sclerosis: A rare congenital disease in which the essential pathology is the appearance of multiple tumors in the cerebrum and in other organs, such as the heart or kidneys. [NIH] Tubocurarine: A neuromuscular blocker and active ingredient in curare; plant based alkaloid of Menispermaceae. [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] Tunica Intima: The innermost coat of blood vessels, consisting of a thin lining of endothelial
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cells longitudinally oriented and continuous with the endothelium of capillaries on the one hand and the endocardium of the heart on the other. [NIH] Type 2 diabetes: Usually characterized by a gradual onset with minimal or no symptoms of metabolic disturbance and no requirement for exogenous insulin. The peak age of onset is 50 to 60 years. Obesity and possibly a genetic factor are usually present. [NIH] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Ulcer: A localized necrotic lesion of the skin or a mucous surface. [NIH] Ulceration: 1. The formation or development of an ulcer. 2. An ulcer. [EU] Ulnar Nerve: A major nerve of the upper extremity. In humans, the fibers of the ulnar nerve originate in the lower cervical and upper thoracic spinal cord (usually C7 to T1), travel via the medial cord of the brachial plexus, and supply sensory and motor innervation to parts of the hand and forearm. [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] Ultrasonography: The visualization of deep structures of the body by recording the reflections of echoes of pulses of ultrasonic waves directed into the tissues. Use of ultrasound for imaging or diagnostic purposes employs frequencies ranging from 1.6 to 10 megahertz. [NIH] Umbilical Arteries: Either of a pair of arteries originating from the internal iliac artery and passing through the umbilical cord to carry blood from the fetus to the placenta. [NIH] Umbilical Cord: The flexible structure, giving passage to the umbilical arteries and vein, which connects the embryo or fetus to the placenta. [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Unresectable: Unable to be surgically removed. [NIH] Uraemia: 1. An excess in the blood of urea, creatinine, and other nitrogenous end products of protein and amino acids metabolism; more correctly referred to as azotemia. 2. In current usage the entire constellation of signs and symptoms of chronic renal failure, including nausea, vomiting anorexia, a metallic taste in the mouth, a uraemic odour of the breath, pruritus, uraemic frost on the skin, neuromuscular disorders, pain and twitching in the muscles, hypertension, edema, mental confusion, and acid-base and electrolyte imbalances. [EU]
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]
Urge urinary incontinence: Urinary leakage when the bladder contracts unexpectedly by itself. [NIH]
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Uric: A kidney stone that may result from a diet high in animal protein. When the body breaks down this protein, uric acid levels rise and can form stones. [NIH] Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urinary Retention: Inability to urinate. The etiology of this disorder includes obstructive, neurogenic, pharmacologic, and psychogenic causes. [NIH] Urinary tract: The organs of the body that produce and discharge urine. These include the kidneys, ureters, bladder, and urethra. [NIH] 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] Uterine Contraction: Contraction of the uterine muscle. [NIH] Uterus: The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called the womb. [NIH] Uveitis: An inflammation of part or all of the uvea, the middle (vascular) tunic of the eye, and commonly involving the other tunics (the sclera and cornea, and the retina). [EU] Uvula: Uvula palatinae; specifically, the tongue-like process which projects from the middle of the posterior edge of the soft palate. [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] Vanadium: Vanadium. A metallic element with the atomic symbol V, atomic number 23, and atomic weight 50.94. It is used in the manufacture of vanadium steel. Prolonged exposure can lead to chronic intoxication caused by absorption usually via the lungs. [NIH] Varicose: The common ulcer in the lower third of the leg or near the ankle. [NIH] Varicose vein: An abnormal swelling and tortuosity especially of the superficial veins of the legs. [EU] 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 Headaches: A group of disorders characterized by recurrent headaches associated
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with abnormal dilation and constriction of cerebral blood vessels. Representative disorders from this category include migraine, cluster headache, and paroxysmal hemicrania. [NIH] Vascular Resistance: An expression of the resistance offered by the systemic arterioles, and to a lesser extent by the capillaries, to the flow of blood. [NIH] Vasculitis: Inflammation of a blood vessel. [NIH] Vasoactive: Exerting an effect upon the calibre of blood vessels. [EU] Vasoactive Intestinal Peptide: A highly basic, single-chain polypeptide isolated from the intestinal mucosa. It has a wide range of biological actions affecting the cardiovascular, gastrointestinal, and respiratory systems. It is also found in several parts of the central and peripheral nervous systems and is a neurotransmitter. [NIH] Vasoconstriction: Narrowing of the blood vessels without anatomic change, for which constriction, pathologic is used. [NIH] Vasodilatation: A state of increased calibre of the blood vessels. [EU] Vasodilation: Physiological dilation of the blood vessels without anatomic change. For dilation with anatomic change, dilatation, pathologic or aneurysm (or specific aneurysm) is used. [NIH] Vasodilator: An agent that widens blood vessels. [NIH] Vasogenic: Acute peripheral circulatory failure due to loss of capillary tone associated with a reduced circulating blood volume. [NIH] Vasomotor: 1. Affecting the calibre of a vessel, especially of a blood vessel. 2. Any element or agent that effects the calibre of a blood vessel. [EU] Vasopressor: 1. Stimulating contraction of the muscular tissue of the capillaries and arteries. 2. An agent that stimulates contraction of the muscular tissue of the capillaries and arteries. [EU]
Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] 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] Ventral: 1. Pertaining to the belly or to any venter. 2. Denoting a position more toward the belly surface than some other object of reference; same as anterior in human anatomy. [EU] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Ventricular: Pertaining to a ventricle. [EU] Ventricular Dysfunction: A condition in which the ventricles of the heart exhibit a
Dictionary 321
decreased functionality. [NIH] Ventricular fibrillation: Rapid, irregular quivering of the heart's ventricles, with no effective heartbeat. [NIH] Ventricular Function: The hemodynamic and electrophysiological action of the ventricles. [NIH]
Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Vertebrae: A bony unit of the segmented spinal column. [NIH] Vertebral: Of or pertaining to a vertebra. [EU] Vertigo: An illusion of movement; a sensation as if the external world were revolving around the patient (objective vertigo) or as if he himself were revolving in space (subjective vertigo). The term is sometimes erroneously used to mean any form of dizziness. [EU] Vestibular: Pertaining to or toward a vestibule. In dental anatomy, used to refer to the tooth surface directed toward the vestibule of the mouth. [EU] Vestibule: A small, oval, bony chamber of the labyrinth. The vestibule contains the utricle and saccule, organs which are part of the balancing apparatus of the ear. [NIH] Vestibulocochlear Nerve: The 8th cranial nerve. The vestibulocochlear nerve has a cochlear part (cochlear nerve) which is concerned with hearing and a vestibular part (vestibular nerve) which mediates the sense of balance and head position. The fibers of the cochlear nerve originate from neurons of the spiral ganglion and project to the cochlear nuclei (cochlear nucleus). The fibers of the vestibular nerve arise from neurons of Scarpa's ganglion and project to the vestibular nuclei. [NIH] Vestibulocochlear Nerve Diseases: Diseases of the vestibular and/or cochlear (acoustic) nerves, which join to form the vestibulocochlear nerve. Vestibular neuritis, cochlear neuritis, and acoustic neuromas are relatively common conditions that affect these nerves. Clinical manifestations vary with which nerve is primarily affected, and include hearing loss, vertigo, and tinnitus. [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] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Viscera: Any of the large interior organs in any one of the three great cavities of the body, especially in the abdomen. [NIH] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] Visceral Afferents: The sensory fibers innervating the viscera. [NIH] Viscosity: A physical property of fluids that determines the internal resistance to shear forces. [EU] Vitreous Body: The transparent, semigelatinous substance that fills the cavity behind the crystalline lens of the eye and in front of the retina. It is contained in a thin hyoid membrane and forms about four fifths of the optic globe. [NIH]
322
Hypotension
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] Weight-Bearing: The physical state of supporting an applied load. This often refers to the weight-bearing bones or joints that support the body's weight, especially those in the spine, hip, knee, and foot. [NIH] Wheezing: Breathing with a rasp or whistling sound; a sign of airway constriction or obstruction. [NIH] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]
Whooping Cough: A respiratory infection caused by Bordetella pertussis and characterized by paroxysmal coughing ending in a prolonged crowing intake of breath. [NIH] Whooping Cough: A respiratory infection caused by Bordetella pertussis and characterized by paroxysmal coughing ending in a prolonged crowing intake of breath. [NIH] Windpipe: A rigid tube, 10 cm long, extending from the cricoid cartilage to the upper border of the fifth thoracic vertebra. [NIH] Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) A substance-specific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] 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] Zoonoses: Diseases of non-human animals that may be transmitted to man or may be transmitted from man to non-human animals. [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]
323
INDEX 1 1-phosphate, 139, 140, 215 A Abdomen, 215, 227, 228, 235, 252, 265, 274, 285, 288, 290, 309, 310, 314, 319, 321 Abdominal, 40, 67, 186, 189, 215, 216, 229, 234, 237, 257, 270, 277, 288, 290, 291, 302, 304 Abdominal Pain, 67, 215, 257, 270, 291 Abducens, 215, 218 Aberrant, 56, 119, 215 Acceptor, 215, 274, 287, 297 Acclimation, 34, 215 Accommodation, 26, 215 Acetylcholine, 120, 124, 133, 137, 140, 215, 284 Acidosis, 64, 148, 161, 215, 244 Acoustic, 185, 215, 321 Actin, 215, 280, 281 Acute renal, 30, 69, 157, 215, 262 Acute tubular, 157, 215 Adaptability, 215, 233 Adaptation, 26, 63, 215, 293 Adenine, 215, 216, 300 Adenocarcinoma, 216, 284 Adenosine, 52, 61, 101, 140, 216, 292 Adenylate Cyclase, 118, 130, 136, 145, 216 Adipocytes, 216, 273 Adjustment, 123, 148, 215, 216 Adolescence, 158, 216, 289 Adrenal Cortex, 216, 217, 240, 241, 252, 263, 296, 302 Adrenal Glands, 216, 219, 302 Adrenal insufficiency, 48, 67, 147, 216 Adrenal Medulla, 42, 114, 216, 232, 251, 252, 285 Adrenaline, 121, 216 Adrenergic Agents, 118, 130, 132, 216 Adrenergic Agonists, 117, 216, 312 Adrenergic Antagonists, 216, 312 Adrenergic Uptake Inhibitors, 216, 306 Adrenoreceptor, 120, 216 Adverse Effect, 48, 49, 216, 307 Aerobic, 31, 44, 216, 253, 287 Aerobic Exercise, 31, 44, 216 Aerosol, 217, 312 Afferent, 10, 19, 23, 32, 35, 46, 56, 217, 273, 309
Affinity, 50, 114, 126, 127, 136, 144, 217, 275, 308 Agar, 217, 237, 293 Age of Onset, 217, 229, 318 Agonist, 14, 27, 30, 109, 113, 136, 164, 217, 229, 246, 251, 255, 278, 292, 313 Agoraphobia, 217, 288, 292 Air Embolism, 158, 217 Air Sacs, 217 Airway, 147, 217, 229, 276, 307, 322 Airway Obstruction, 148, 217, 276 Albumin, 90, 217, 293 Aldosterone, 30, 60, 90, 150, 217, 278 Alertness, 217, 285 Algorithms, 218, 227 Alimentary, 218, 269, 271, 288 Alkaline, 215, 218, 219, 230, 287 Alkaloid, 218, 224, 230, 279, 317 Alleles, 61, 218 Allergens, 36, 218, 256 Alopecia, 25, 218 Alpha Particles, 218, 300 Alpha-1, 14, 218, 239, 246 Alternans, 8, 218 Alternative medicine, 164, 218 Alveolitis, 33, 218 Amaurosis, 75, 218 Amaurosis Fugax, 75, 218 Ameliorating, 126, 127, 140, 218 Amenorrhea, 218, 221 Amifostine, 203, 218 Amine, 218, 263 Amino Acid Sequence, 144, 218, 221, 296 Amino Acid Substitution, 33, 218 Amino Acids, 127, 140, 218, 219, 220, 289, 294, 298, 306, 312, 318 Ammonia, 218, 219, 312, 318 Amnesia, 126, 219 Amniotic Fluid, 219, 258, 276 Amplification, 18, 219 Ampulla, 219, 250 Amputation, 186, 219 Amyloid, 219, 234 Amyloidosis, 97, 151, 219 Anaemia, 86, 219 Anaesthesia, 68, 70, 71, 74, 77, 78, 80, 90, 91, 92, 95, 96, 101, 219, 267 Anal, 24, 219
324
Hypotension
Analgesic, 59, 126, 127, 133, 219, 279, 286 Analog, 25, 61, 219, 236, 271 Analogous, 219, 247, 317 Anaphylatoxins, 219, 238 Anaphylaxis, 129, 219 Anatomical, 46, 56, 220, 223, 228, 239, 245, 266, 283, 288, 305 Androgens, 216, 220, 241 Anemia, 3, 50, 54, 78, 134, 151, 152, 158, 181, 197, 220, 227, 236, 261 Anergy, 220, 312 Anesthetics, 220, 225, 252 Aneurysm, 187, 220, 320 Angina, 7, 23, 112, 119, 130, 134, 139, 140, 142, 148, 154, 188, 190, 220, 284 Angina Pectoris, 7, 112, 119, 130, 134, 139, 140, 142, 148, 154, 220 Angiogenesis, 139, 220 Angiography, 4, 78, 220 Angiopathy, 220, 234 Angioplasty, 4, 84, 91, 139, 220, 223, 281 Angiotensin-Converting Enzyme Inhibitors, 81, 220 Angiotensinogen, 220, 302 Animal model, 4, 20, 26, 43, 61, 63, 132, 220 Anions, 217, 221, 270, 307, 312 Ankle, 122, 221, 319 Annealing, 221, 294 Anomalies, 157, 221 Anorexia, 86, 112, 119, 130, 134, 137, 139, 140, 221, 248, 257, 318 Anorexia Nervosa, 86, 130, 221 Anoxia, 113, 221 Antagonism, 126, 127, 221 Antiallergic, 221, 241 Antiarrhythmic, 7, 221 Antibacterial, 221, 236, 309 Antibiotic, 221, 274, 289, 309 Antibodies, 36, 39, 117, 221, 252, 260, 262, 263, 266, 275, 279, 293, 301 Antibody, 39, 132, 217, 221, 222, 237, 260, 263, 264, 266, 267, 276, 279, 300, 301, 309 Anticholinergic, 45, 141, 221, 234, 292 Anticoagulant, 221, 298 Antidepressant, 60, 127, 221 Antidote, 50, 221, 308 Antiemetic, 221, 264 Antigen, 36, 217, 218, 219, 221, 222, 238, 252, 263, 264, 266, 267, 268, 276, 300 Antigen-Antibody Complex, 222, 238
Antihypertensive, 10, 43, 120, 148, 222, 255, 260, 263 Anti-infective, 222, 230, 264 Anti-inflammatory, 32, 55, 86, 222, 241, 244, 256, 258, 271, 296 Anti-Inflammatory Agents, 222, 241, 271 Antineoplastic, 222, 241, 287 Antioxidant, 34, 55, 222, 223, 287 Antipruritic, 222, 230 Antiviral, 222, 268, 289 Anuria, 222, 272 Anus, 219, 222, 228, 269, 301 Anxiety, 61, 112, 119, 124, 130, 135, 137, 139, 149, 196, 222, 264, 288, 292 Anxiety Disorders, 222, 288 Anxiolytic, 123, 124, 143, 222, 229 Aorta, 60, 222, 231, 240, 296, 302, 320 Apathy, 150, 222 Apnea, 3, 59, 191, 222 Apolipoproteins, 222, 274 Aponeurosis, 222, 257 Apoptosis, 19, 28, 55, 64, 222 Applicability, 49, 222 Aqueous, 27, 50, 222, 225, 227, 236, 242, 249, 256, 264, 273, 316 Aqueous humor, 27, 222, 227, 236, 316 Arachidonic Acid, 222, 241, 248, 273, 297 Arginine, 29, 32, 65, 100, 116, 120, 219, 223, 284 Aromatic, 121, 223, 291 Arrhythmia, 21, 141, 187, 221, 223 Arterial, 6, 9, 12, 17, 19, 21, 23, 28, 30, 31, 35, 46, 49, 54, 68, 69, 72, 75, 80, 81, 85, 95, 96, 120, 121, 149, 223, 234, 235, 240, 264, 270, 284, 298, 313 Arteries, 29, 125, 187, 220, 222, 223, 227, 228, 240, 269, 271, 274, 278, 281, 299, 314, 318, 320 Arteriolar, 21, 42, 223, 228, 255, 302 Arterioles, 41, 54, 223, 227, 230, 278, 281, 320 Arteriosus, 223, 299 Arteriovenous, 152, 223, 234, 278 Arteriovenous Fistula, 152, 223 Articular, 223, 286 Ascites, 150, 151, 223 Ascorbic Acid, 129, 223 Aspartate, 11, 223, 271 Assay, 223, 266, 300 Asymptomatic, 81, 154, 166, 223, 288 Ataxia, 180, 181, 223, 314 Atherectomy, 223, 249
Index 325
Atrial, 128, 189, 223, 240, 317 Atrial Fibrillation, 189, 223 Atrioventricular, 223, 240 Atrium, 223, 231, 240, 317, 320 Atrophy, 12, 100, 107, 108, 180, 184, 224, 283 Atropine, 45, 224, 225 Attenuated, 6, 7, 224, 245 Attenuation, 43, 224 Atypical, 38, 167, 224, 285 Auditory, 10, 185, 224, 253, 319 Autodigestion, 224, 288 Autoimmune disease, 224, 280 Autoimmunity, 119, 134, 224 Autonomic Denervation, 153, 224 Autonomic Dysreflexia, 189, 224 Autonomic Nervous System, 4, 6, 24, 63, 184, 224, 225, 290, 308, 312 Autonomic Neuropathy, 4, 26, 39, 81, 90, 96, 152, 166, 186, 224 Autoradiography, 32, 224 Axillary, 62, 224, 228 Axons, 224, 282, 286, 296, 303, 309 B Babesiosis, 84, 224 Bacterial Infections, 224, 233, 260, 303 Bacterial Physiology, 215, 225 Bactericidal, 38, 225, 252 Bacteriophage, 225, 293, 317 Bacterium, 13, 38, 225, 262, 316 Barbiturate, 154, 225 Baroreflex, 7, 9, 10, 12, 17, 21, 31, 43, 225 Basal Ganglia, 223, 225, 228, 234, 235, 257, 265 Basal Ganglia Diseases, 223, 225, 235, 265 Base, 41, 77, 138, 155, 162, 215, 225, 243, 271, 272, 313, 318 Bed Rest, 58, 88, 225 Belladonna, 224, 225 Benign prostatic hyperplasia, 114, 115, 116, 153, 191, 202, 225 Benzene, 225, 232 Benzodiazepines, 124, 225, 229 Beta 2-Microglobulin, 156, 225 Beta blocker, 167, 226 Beta-Thromboglobulin, 226, 269 Bewilderment, 226, 238 Bilateral, 10, 28, 67, 70, 226, 288 Bile, 226, 256, 263, 271, 274, 276, 310 Bile Pigments, 226, 271, 276 Biliary, 226, 230, 288 Biliary Tract, 226, 230, 288
Bilirubin, 55, 217, 226, 264 Binding Sites, 20, 33, 226 Bioassays, 15, 226 Biochemical, 16, 24, 45, 48, 54, 218, 226, 272, 273, 286, 306 Biological response modifier, 119, 226, 268 Biological therapy, 226, 260 Biological Transport, 226, 245 Biopsy, 186, 226, 290 Biopterin, 22, 226 Biosynthesis, 44, 48, 223, 226, 242, 306 Biotechnology, 64, 66, 164, 177, 179, 180, 181, 226 Biotransformation, 227 Biphasic, 17, 227 Bipolar Disorder, 198, 227 Bladder, 92, 148, 154, 224, 225, 227, 242, 267, 280, 283, 290, 297, 298, 303, 318, 319 Blastocyst, 227, 238, 249, 293 Bloating, 227, 257, 270 Blood Cell Count, 227, 261 Blood Coagulation, 227, 230, 314 Blood Flow Velocity, 21, 227 Blood Glucose, 35, 148, 154, 159, 227, 262, 265, 268 Blood Platelets, 227, 293, 306, 314 Blood transfusion, 46, 71, 151, 227, 262 Blood Viscosity, 227, 262 Blood Volume, 12, 30, 31, 49, 72, 96, 117, 120, 227, 231, 320 Blood-Aqueous Barrier, 227, 256 Blood-Brain Barrier, 113, 227, 273, 282, 292, 313 Blood-Retinal Barrier, 228, 256 Body Composition, 24, 228 Body Fluids, 228, 247, 308 Body Regions, 228, 237 Bolus, 136, 228 Bolus infusion, 228 Bolus injection, 136, 228 Bone Marrow, 49, 55, 225, 228, 237, 252, 260, 266, 275, 279, 280, 308 Bone metastases, 228, 301 Bowel, 118, 134, 219, 228, 245, 251, 267, 290, 311 Bowel Movement, 228, 245, 311 Brachial, 228, 276, 300, 318 Brachial Artery, 228, 300 Brachial Plexus, 228, 276, 300, 318 Brachytherapy, 228, 269, 300 Bradycardia, 15, 19, 21, 24, 56, 65, 72, 74, 79, 85, 121, 228, 255
326
Hypotension
Bradykinin, 10, 32, 120, 228, 271, 284, 293 Brain Hypoxia, 27, 228, 314 Brain Neoplasms, 228, 311, 314 Brain Stem, 47, 59, 228, 229, 233, 304 Branch, 54, 79, 101, 211, 229, 248, 275, 289, 299, 302, 309, 314, 315 Breakdown, 11, 158, 229, 244, 245, 257, 286 Breast Feeding, 36, 229 Bronchi, 229, 252, 271, 316 Bronchial, 229, 263 Bronchiseptica, 229, 291 Bronchitis, 229, 235 Bronchodilator, 229, 271, 313 Bronchospasm, 89, 229 Buffers, 225, 229 Bulimia, 112, 119, 130, 134, 139, 140, 229, 306 Buspirone, 124, 229 C Cachexia, 119, 130, 134, 144, 229 Caesarean section, 77, 80, 95, 229 Calcification, 39, 229 Calcineurin, 12, 229 Calcium channel blocker, 89, 230 Calcium Channel Blockers, 89, 230 Calcium Channels, 24, 64, 145, 230 Calculi, 230, 259 Calmodulin, 229, 230 Caloric intake, 8, 230 Camphor, 71, 75, 230 Camptothecin, 230, 270 Capillary, 46, 54, 227, 228, 230, 258, 320, 321 Capillary Permeability, 228, 230 Capsaicin, 133, 230 Carbohydrate, 101, 230, 241, 258, 259, 294, 306 Carbon Dioxide, 49, 230, 231, 232, 243, 257, 264, 265, 293, 303, 320 Carboxy, 142, 231 Carcinogenesis, 153, 231 Carcinogenic, 225, 231, 267, 284, 285, 296, 308, 310 Carcinogens, 231, 235, 285 Carcinoma, 203, 231, 284, 310 Cardiac arrest, 113, 147, 154, 231, 311 Cardiac Output, 21, 29, 120, 225, 231, 311 Cardiogenic, 29, 231 Cardiology, 79, 113, 187, 188, 189, 195, 196, 231 Cardiomyopathy, 61, 152, 231
Cardiopulmonary, 14, 19, 67, 83, 85, 89, 113, 148, 158, 231, 262 Cardiopulmonary Bypass, 14, 67, 83, 85, 89, 231, 262 Cardiopulmonary Resuscitation, 113, 148, 231 Cardiorespiratory, 46, 153, 217, 231 Cardiotonic, 231, 292 Cardiovascular Agents, 24, 231 Cardiovascular disease, 3, 6, 54, 116, 119, 120, 134, 135, 136, 159, 231 Cardiovascular Physiology, 16, 231 Cardiovascular System, 30, 32, 135, 137, 159, 224, 231 Carnitine, 156, 232 Carotene, 232, 303 Carotid Body, 232, 234 Carotid Sinus, 10, 16, 187, 232, 258, 296 Carotid Stenosis, 95, 232 Carpal Tunnel Syndrome, 151, 154, 232 Carrier Proteins, 232, 293, 301 Case report, 73, 79, 83, 93, 94, 232, 236, 254 Case series, 38, 232, 236 Catecholamine, 42, 96, 121, 129, 232, 246, 291 Catechols, 72, 88, 232 Catheterization, 78, 79, 220, 232, 270, 281 Cathode, 232, 248 Cations, 133, 232, 270 Caudal, 100, 232, 245, 265, 295 Causal, 52, 232, 262, 314 Causality, 38, 232 Cause of Death, 11, 41, 113, 120, 152, 233 Cell Adhesion, 233, 268 Cell Aggregation, 54, 233 Cell Cycle, 233, 236, 299 Cell Death, 18, 19, 28, 222, 233, 282 Cell Differentiation, 119, 135, 233, 307 Cell Division, 180, 224, 233, 260, 276, 279, 293, 297 Cell membrane, 226, 230, 232, 233, 244, 292, 295 Cell proliferation, 119, 135, 155, 233, 269, 307 Cell Respiration, 233, 287, 303 Cell Survival, 233, 260 Central Nervous System Diseases, 140, 233 Central Nervous System Infections, 233, 260 Centrifugation, 233, 261 Cerebellar, 63, 223, 233, 302, 317
Index 327
Cerebellum, 63, 228, 233, 256, 294, 302 Cerebral Aqueduct, 233, 256, 290, 314 Cerebral hemispheres, 225, 228, 229, 233, 234 Cerebral Hemorrhage, 142, 234 Cerebral Infarction, 234 Cerebral Palsy, 48, 234, 309 Cerebrospinal, 5, 32, 72, 74, 82, 90, 92, 234, 241, 311 Cerebrospinal fluid, 5, 32, 72, 74, 82, 90, 92, 234, 241, 311 Cerebrovascular, 7, 26, 35, 126, 142, 148, 151, 225, 230, 231, 234, 284, 314 Cerebrum, 233, 234, 317 Cervical, 10, 78, 82, 92, 93, 228, 234, 261, 274, 276, 300, 310, 318 Cervix, 234 Cesarean Section, 40, 92, 234 Cetirizine, 234, 264 Character, 220, 234, 243, 300 Chelating Agents, 143, 234 Chemoreceptor, 31, 234 Chemotactic Factors, 234, 238 Chemotherapy, 187, 191, 203, 234, 235, 304 Chest Pain, 137, 147, 193, 235 Chest wall, 235, 294, 314 Chiropractic, 76, 82, 235 Chlorophyll, 234, 235 Cholesterol, 226, 235, 240, 246, 247, 264, 274, 310 Cholesterol Esters, 235, 274 Chorea, 126, 127, 235 Choreatic Disorders, 235 Choroid, 235, 239, 303 Chromatin, 222, 235, 251 Chromic, 27, 235 Chromium, 235 Chromosomal, 219, 235 Chronic Disease, 7, 119, 134, 229, 235, 237 Chronic Fatigue Syndrome, 50, 62, 235 Chronic Obstructive Pulmonary Disease, 129, 194, 235 Chronic renal, 23, 157, 161, 235, 294, 318 Chronotropic, 113, 235 Chylomicrons, 235, 274 Ciliary, 27, 222, 223, 227, 235, 236, 306 Ciliary Body, 27, 223, 227, 236, 306 Ciliary processes, 222, 236 Circulatory system, 128, 217, 236, 250, 270 CIS, 55, 236, 303 Cisplatin, 25, 236 Citrus, 223, 236
Clamp, 10, 27, 52, 236 Clindamycin, 155, 236 Clinical Medicine, 5, 236, 295 Clinical study, 107, 108, 236 Clinical trial, 5, 17, 25, 37, 41, 58, 61, 73, 107, 108, 109, 166, 177, 236, 239, 298, 301 Clone, 130, 236 Cloning, 112, 140, 226, 236 Coagulation, 155, 227, 236, 262, 293, 315 Cobalt, 51, 236 Cochlear, 236, 237, 315, 321 Cochlear Diseases, 237, 315 Coenzyme, 223, 237 Cofactor, 237, 298, 314 Cognition, 137, 237 Colic, 36, 129, 237, 278 Colitis, 237, 267, 270 Collagen, 237, 255, 257, 263, 293 Collagen disease, 237, 263 Collapse, 22, 46, 220, 229, 237, 294, 307 Colloidal, 217, 237, 248, 253, 307, 312 Colony-Stimulating Factors, 200, 237, 259 Colorectal, 203, 237 Combination Therapy, 25, 148, 237 Comorbidity, 39, 237 Complement, 5, 32, 129, 219, 237, 257, 268, 275, 279, 293 Compress, 238, 316 Compulsive Behavior, 238, 306 Computational Biology, 177, 179, 238 Computed tomography, 200, 238 Computerized axial tomography, 238 Computerized tomography, 238 Conception, 238, 255, 296 Concomitant, 30, 166, 238 Conduction, 52, 149, 238, 283 Cones, 238, 303 Confounding, 20, 57, 101, 238 Confusion, 93, 158, 238, 246, 265, 318 Congestive heart failure, 56, 112, 129, 139, 148, 150, 192, 239 Conjunctiva, 239, 267, 292, 317 Connective Tissue, 223, 228, 237, 239, 255, 256, 257, 275, 279, 304, 313 Connexin 43, 65, 239 Consciousness, 147, 219, 239, 243, 246, 285, 303, 313 Constipation, 151, 239, 270, 291 Constriction, 42, 121, 232, 239, 270, 320, 322 Constriction, Pathologic, 239, 320 Consultation, 134, 239
328
Hypotension
Consumption, 239, 244, 257, 285, 287 Contingent Negative Variation, 76, 239 Continuum, 26, 239 Contractility, 7, 30, 51, 220, 239 Contraindications, ii, 120, 239 Contralateral, 218, 239, 277, 286, 302 Control group, 36, 62, 239 Controlled study, 51, 239 Contusion, 79, 239 Conus, 239, 299 Convulsions, 225, 239, 247, 265, 296, 309 Convulsive, 154, 239 Coordination, 129, 233, 234, 239, 280 Cor, 76, 240, 297 Cornea, 222, 240, 248, 311, 319 Coronary, 4, 7, 14, 20, 23, 39, 120, 139, 142, 190, 196, 201, 220, 231, 240, 264, 278, 281, 284 Coronary Arteriosclerosis, 240, 281 Coronary Artery Bypass, 4, 240 Coronary Circulation, 220, 240, 284 Coronary Disease, 4, 240 Coronary heart disease, 231, 240 Coronary Thrombosis, 240, 278, 281 Coronary Vessels, 7, 240 Corpus, 166, 240, 289, 296, 314 Corpus Luteum, 240, 296 Corrosion, 69, 240 Cortex, 52, 60, 223, 240, 253, 254, 302 Cortical, 10, 154, 239, 240, 253, 305, 314 Corticosteroid, 39, 240, 295 Cortisol, 5, 48, 59, 217, 241 Cortisone, 241, 244, 296 Cranial, 92, 154, 233, 241, 258, 260, 270, 283, 286, 290, 309, 317, 319, 321 Craniocerebral Trauma, 225, 234, 241, 260, 311, 314, 315 Criterion, 51, 241 Critical Care, 29, 58, 113, 156, 192, 241 Critical Illness, 5, 241 Crystallization, 16, 241 CSF, 5, 61, 74, 95, 226, 234, 237, 241, 259, 269, 270, 275 Cues, 63, 241 Cumulative Trauma Disorders, 241, 279 Curative, 116, 241, 314 Cutaneous, 59, 148, 152, 186, 241, 265, 275, 300 Cyanide, 50, 241, 308 Cyanosis, 241, 276 Cyclic, 10, 81, 166, 216, 230, 241, 260, 284, 292, 297, 305
Cyclooxygenase Inhibitors, 48, 241 Cystathionine beta-Synthase, 242, 264 Cysteine, 57, 140, 242, 246, 312 Cystine, 242, 246 Cystitis, 129, 242 Cytochrome, 242, 303 Cytochrome b, 242, 303 Cytokine, 5, 13, 14, 16, 18, 32, 42, 47, 53, 65, 115, 116, 119, 242, 269 Cytomegalovirus, 140, 242 Cytopenia, 119, 134, 242 Cytoplasm, 222, 233, 242, 251, 253, 260, 279 Cytoskeleton, 242, 268, 278 Cytostatic, 116, 242 Cytotoxic, 230, 242, 269, 301, 307 Cytotoxicity, 53, 236, 242 D Data Collection, 24, 96, 242 Databases, Bibliographic, 177, 242 De novo, 42, 87, 243 Decarboxylation, 243, 263 Decidua, 243, 293 Decompensation, 13, 243 Decongestant, 243, 292 Defense Mechanisms, 38, 243, 268 Deferoxamine, 143, 243 Degenerative, 139, 184, 239, 243, 262, 279, 286, 303 Dehydration, 157, 243 Deletion, 222, 243 Delirium, 112, 119, 130, 135, 139, 143, 243 Delivery of Health Care, 243, 261 Dementia, 93, 112, 119, 126, 127, 130, 135, 139, 144, 192, 243 Denaturation, 243, 294 Dendrites, 243, 283 Dendritic, 243, 277, 303 Density, 137, 233, 243, 247, 274, 285, 294, 308 Dental Caries, 243, 256 Depersonalization, 244, 288, 305 Depolarization, 244, 307 Depressive Disorder, 198, 203, 244 Deprivation, 113, 244 Derealization, 244, 288 Dermatitis, 118, 134, 244, 248, 264 Detoxification, 124, 244 Deuterium, 244, 263 Developed Countries, 45, 151, 244 Dexamethasone, 48, 244 Diabetes Insipidus, 126, 127, 244
Index 329
Diabetes Mellitus, 4, 9, 125, 148, 151, 158, 186, 198, 201, 202, 244, 258, 262 Diabetes, Gestational, 148, 244, 296 Diabetic Ketoacidosis, 148, 244 Diabetic Retinopathy, 151, 244, 292 Diagnostic procedure, 111, 165, 244 Dialysate, 62, 70, 245 Dialyzer, 114, 117, 131, 156, 158, 245, 261 Diarrhea, 36, 155, 186, 245, 251, 270, 272, 278 Diarrhoea, 66, 245, 257 Diastole, 245 Diastolic, 39, 121, 152, 245, 264 Diastolic pressure, 121, 245, 264 Diencephalon, 233, 245, 265, 314 Diffusion, 11, 52, 58, 226, 230, 245, 260, 267, 302, 318 Digestion, 6, 218, 226, 228, 245, 247, 257, 274, 289, 310 Digestive system, 110, 245 Digestive tract, 224, 245, 307, 310 Dihydrotestosterone, 245, 302 Dilatation, 101, 220, 245, 269, 296, 320 Dilatation, Pathologic, 245, 320 Dilate, 125, 245 Dilated cardiomyopathy, 54, 245 Dilation, 7, 223, 228, 245, 320 Dilator, 245, 284 Dilution, 21, 41, 245, 252, 293 Direct, iii, 7, 10, 14, 25, 27, 49, 54, 58, 169, 236, 245, 246, 263, 300, 302, 313 Disease Susceptibility, 112, 245 Disinfectant, 89, 245, 252 Diskectomy, 82, 245 Disorientation, 239, 243, 246 Dissociation, 47, 217, 246 Dissociative Disorders, 246 Distal, 62, 240, 246, 248, 290, 296, 299 Disulphide, 118, 246 Diuresis, 12, 15, 127, 144, 246 Diuretic, 200, 246, 276, 308 Dizziness, 4, 7, 107, 108, 123, 124, 137, 143, 185, 186, 187, 246, 288, 321 Domesticated, 246, 260 Dominance, 246, 272 Dopa, 246, 273 Dopamine, 27, 28, 42, 118, 127, 130, 132, 137, 140, 164, 246, 255, 273, 291 Dorsal, 59, 246, 295, 309 Dorsum, 246, 257 Dose-dependent, 71, 109, 246 Dose-limiting, 67, 90, 109, 246
Doxazosin, 153, 246 Drive, ii, vi, 3, 19, 49, 99, 147, 149, 152, 156, 247 Drug Design, 119, 171, 247 Drug Interactions, 149, 153, 170, 247 Drug Tolerance, 247, 315 Duct, 219, 232, 247, 253, 304, 312 Duodenum, 226, 247, 250, 257, 289, 310 Dura mater, 247, 252 Dyes, 219, 247, 284, 312 Dynorphins, 247, 285 Dyskinesia, 247 Dyslipidemia, 4, 148, 159, 247 Dyspepsia, 166, 247 Dysphoria, 39, 247 Dysphoric, 38, 244, 247 Dysplasia, 181, 247 Dyspnea, 243, 247, 288 Dyspnoea, 67, 247 Dystrophy, 180, 247 E Eating Disorders, 198, 247 Eclampsia, 226, 247, 296 Eczema, 36, 248 Edema, 11, 21, 122, 150, 243, 244, 248, 270, 281, 296, 318 Effector, 38, 42, 118, 130, 132, 136, 140, 215, 237, 248, 283, 284, 292 Effector cell, 38, 248, 283, 284 Efficacy, 8, 12, 18, 45, 47, 61, 75, 77, 109, 113, 153, 229, 247, 248 Ehrlichiosis, 38, 248 Eicosanoids, 150, 241, 248 Elasticity, 113, 240, 248 Elective, 66, 88, 92, 101, 248 Electric shock, 113, 231, 248 Electrochemistry, 43, 248 Electrocoagulation, 236, 248 Electrode, 122, 232, 248 Electrolysis, 221, 232, 248, 249 Electrolyte, 117, 131, 155, 158, 217, 241, 243, 248, 262, 272, 278, 295, 308, 318 Electrons, 222, 225, 232, 248, 270, 287, 300, 301 Electronystagmography, 185, 248 Electrophoresis, 51, 248 Electrophysiological, 19, 23, 56, 248, 321 Electroplating, 249, 312 Emboli, 157, 249 Embolism, 122, 187, 249, 270, 299 Embolization, 157, 249 Embolus, 249, 267
330
Hypotension
Embryo, 227, 233, 249, 267, 296, 309, 318 Embryo Transfer, 249, 296 Emphysema, 235, 249 Empirical, 39, 249 Emulsion, 224, 249 Encephalitis, 32, 249, 271 Encephalitis, Viral, 249 Encephalopathy, 150, 249 Endarterectomy, 10, 95, 220, 223, 249 Endemic, 249, 309 Endocarditis, 85, 152, 250 Endocardium, 250, 318 Endocrine Glands, 126, 250 Endocrine System, 250, 283 Endocrinology, 5, 67, 101, 120, 250 Endonucleases, 20, 250 Endorphins, 250, 285, 297 Endoscope, 250 Endoscopic, 68, 156, 250 Endoscopy, 156, 250 Endothelial cell, 29, 32, 65, 116, 120, 227, 228, 250, 269, 314, 318 Endothelium, 22, 29, 52, 54, 116, 120, 250, 284, 318 Endothelium, Lymphatic, 250 Endothelium, Vascular, 250 Endothelium-derived, 22, 116, 250, 284 Endotoxemia, 55, 57, 150, 250 Endotoxic, 55, 57, 143, 250 Endotoxin, 20, 55, 57, 65, 115, 119, 120, 143, 250, 317 End-stage renal, 23, 62, 152, 235, 251, 294 Energetic, 11, 251 Energy balance, 7, 8, 251, 273 Energy Intake, 6, 251 Enhancer, 53, 126, 127, 251 Enkephalins, 251, 285 Enterocolitis, 36, 251 Enterotoxins, 16, 251 Environmental Exposure, 251, 285 Environmental Health, 176, 178, 251 Enzymatic, 51, 157, 230, 232, 238, 243, 251, 255, 263, 294, 303 Enzyme Inhibitors, 251, 293 Eosinophilia, 251, 254 Eosinophilic, 36, 251, 254 Eosinophilic Gastroenteritis, 36, 251 Eosinophils, 251, 260, 273 Ephedrine, 66, 77, 90, 121, 251 Epidemic, 159, 251, 309 Epidemiological, 251, 254 Epidermal, 40, 251, 271, 277
Epidermis, 251, 271 Epidural, 12, 70, 75, 77, 78, 80, 91, 93, 252 Epidural Space, 75, 252 Epigastric, 252, 288 Epinephrine, 17, 78, 114, 116, 136, 216, 246, 252, 271, 285, 318 Epithelial, 16, 36, 216, 226, 236, 243, 252, 262, 269, 278 Epithelial Cells, 36, 252, 262, 269, 278 Epithelium, 16, 227, 250, 252, 257 Epitopes, 36, 252 Equipment and Supplies, 117, 131, 158, 252 Erectile, 121, 125, 141, 145, 148, 157, 166, 202, 252, 289 Erection, 125, 145, 157, 252, 292, 296 Erythema, 252, 319 Erythrocyte Volume, 227, 252 Erythrocytes, 219, 220, 224, 227, 228, 252, 262, 301 Erythropoietin, 78, 94, 151, 156, 252 Esophagitis, 156, 252 Esophagus, 245, 252, 289, 291, 310 Essential Tremor, 180, 252 Estradiol, 60, 252 Estrogen, 30, 59, 252 Ethanol, 25, 43, 252 Ethanolamine, 253, 278 Ether, 142, 253 Eukaryotic Cells, 253, 266, 286 Evacuation, 239, 253, 257 Evoke, 15, 253, 310 Evoked Potentials, 185, 253 Excitation, 41, 234, 253 Excitatory, 23, 35, 253, 259 Excrete, 222, 253, 272 Exercise Test, 188, 253 Exhaustion, 221, 253 Exocrine, 253, 288 Exogenous, 13, 22, 30, 135, 227, 248, 253, 298, 318 Exons, 61, 253 Exotoxin, 155, 253 Expander, 253 Expiration, 253, 303 Extender, 253, 293 Extensor, 253, 299, 300 External-beam radiation, 253, 300 Extracellular, 23, 28, 30, 53, 56, 64, 120, 140, 141, 152, 219, 239, 254, 255, 268, 278, 308 Extracellular Matrix, 239, 254, 255, 268
Index 331
Extracellular Space, 254, 278 Extracorporeal, 14, 117, 131, 158, 254, 262 Extracorporeal Circulation, 14, 254 Extraction, 80, 117, 131, 234, 254 Extrapyramidal, 246, 254 Extravascular, 40, 254 Extremity, 148, 228, 254, 276, 288, 300, 305, 318 F Facial, 167, 218, 254, 308 Facial Pain, 167, 254 Facial Paralysis, 218, 254 Faecal, 245, 254 Family Planning, 177, 254 Fasciitis, 16, 155, 254 Fat, 216, 220, 222, 228, 232, 240, 241, 249, 254, 271, 273, 274, 280, 304, 308 Fatal Outcome, 44, 254 Fatigue, 4, 21, 50, 121, 150, 235, 254, 261 Fatty acids, 217, 244, 248, 255, 274, 276, 297, 314 Febrile, 150, 158, 255 Feces, 239, 254, 255, 311 Femoral, 231, 255 Femoral Artery, 231, 255 Fenoldopam, 30, 255 Fertilization in Vitro, 255, 296 Fertilizers, 255, 284, 312 Fetal Blood, 31, 255 Fetal Distress, 40, 255 Fetus, 12, 25, 32, 60, 234, 252, 255, 276, 293, 296, 309, 310, 318, 319 Fibrillation, 21, 255 Fibrin, 227, 255, 291, 314 Fibrinogen, 255, 293, 314 Fibrinolysis, 32, 255 Fibroblasts, 254, 255, 269 Fibrosarcoma, 254, 255 Fibrosis, 139, 181, 255, 305 Fibula, 255, 295 Filtration, 21, 255, 259, 272 Fistula, 82, 185, 255 Flatus, 255, 257 Fludrocortisone, 26, 62, 170, 256 Fluorine, 126, 127, 256 Fluorophotometry, 27, 256 Flushing, 166, 256 Fold, 16, 256, 277, 285, 287 Food Hypersensitivity, 36, 256 Foot Care, 152, 256 Foot Ulcer, 148, 186, 256 Foramen, 256, 290
Forearm, 41, 227, 254, 256, 276, 300, 301, 318 Fossa, 122, 233, 256 Fourth Ventricle, 13, 234, 256, 274, 314 Frostbite, 256, 291 Fungi, 256, 278, 310, 322 G Gadolinium, 75, 256 Gallbladder, 23, 215, 226, 245, 256 Gamma Rays, 256, 300, 301 Ganglia, 215, 218, 225, 256, 282, 290, 309, 310, 312 Ganglion, 27, 165, 256, 286, 303, 310, 321 Gangrene, 152, 257 Gas exchange, 257, 303, 320 Gastric, 26, 165, 224, 232, 257, 263, 289, 311 Gastric Emptying, 257 Gastric Juices, 257, 289 Gastric Mucosa, 165, 257 Gastrin, 257, 263 Gastroenteritis, 157, 257 Gastrointestinal tract, 138, 252, 257, 272, 273, 306, 310 Gastroparesis, 152, 186, 257 Gelatin, 257, 259, 314 Gene Expression, 18, 22, 42, 53, 61, 65, 181, 257 Genetic Counseling, 148, 257 Genetic Engineering, 226, 236, 257 Genetic testing, 257, 294 Genetics, 112, 246, 257 Genital, 157, 224, 257, 258, 319 Genitourinary, 153, 258, 319 Genomics, 31, 112, 140, 258 Genotype, 28, 258, 291 Geriatric, 6, 83, 87, 89, 95, 100, 101, 148, 197, 258 Gestation, 258, 293, 309 Gestational, 258, 276 Gestational Age, 258, 276 Gland, 5, 216, 241, 258, 275, 288, 292, 297, 305, 310, 312, 315 Glomerular, 258, 272, 276, 302 Glomerular Filtration Rate, 258, 272, 276 Glomeruli, 258 Glomerulonephritis, 158, 161, 258 Glomerulus, 258, 282 Glossopharyngeal Nerve, 254, 258 Glottis, 258, 291 Glucocorticoid, 244, 258, 263, 278, 295, 296 Gluconeogenesis, 258 Glucose Intolerance, 244, 258
332
Hypotension
Glucose tolerance, 244, 258, 259, 296 Glutamate, 25, 27, 28, 52, 64, 133, 259 Glycine, 259, 306 Glycogen, 259 Glycoprotein, 66, 252, 255, 259, 275, 314, 317 Gonadal, 259, 310 Goniotomy, 259, 316 Gout, 126, 128, 259 Governing Board, 259, 295 Gp120, 259, 289 Graft, 81, 259, 263, 281 Grafting, 240, 259, 266 Gram-negative, 229, 250, 259 Gram-Negative Bacteria, 250, 259 Gram-positive, 13, 259, 311 Gram-Positive Bacteria, 13, 259 Granulocyte Colony-Stimulating Factor, 237, 259 Granulocyte-Macrophage ColonyStimulating Factor, 237, 259 Granulocytes, 237, 259, 260, 273, 307, 322 Granulocytopenia, 25, 260 Granuloma, 78, 260 Granulomatous Disease, Chronic, 260, 303 Gravis, 129, 260, 282 Growth factors, 53, 119, 125, 135, 140, 260 Guanethidine, 101, 260 Guanylate Cyclase, 54, 120, 260, 284 Guinea Pigs, 120, 260 H Habitual, 6, 7, 234, 260 Haematoma, 94, 260 Haemodialysis, 71, 72, 155, 260 Half-Life, 47, 260 Haptens, 217, 260, 300 Headache, 73, 86, 89, 92, 93, 94, 134, 150, 166, 167, 218, 248, 260, 261, 265, 267, 320 Headache Disorders, 167, 260, 261 Head-Down Tilt, 58, 261 Health Care Costs, 48, 261 Health Expenditures, 261 Health Status, 39, 62, 185, 261 Heart Arrest, 231, 261 Heart attack, 126, 154, 187, 231, 261 Heartbeat, 261, 311, 321 Hematemesis, 156, 261 Hematocrit, 54, 155, 156, 227, 261 Heme, 55, 57, 226, 242, 261, 287 Hemicrania, 261, 320 Hemin, 143, 261 Hemiplegia, 218, 261
Hemodiafiltration, 261, 318 Hemodialyzer, 117, 131, 261 Hemodilution, 29, 49, 73, 262 Hemodynamics, 5, 34, 35, 44, 262 Hemofiltration, 155, 261, 262, 318 Hemoglobin, 3, 54, 57, 220, 227, 234, 241, 252, 261, 262, 287 Hemoglobin A, 234, 262 Hemoglobinuria, 180, 262 Hemolysins, 16, 262 Hemolysis, 84, 158, 224, 262 Hemolytic, 254, 262 Hemostasis, 154, 156, 262, 268, 306 Hepatic, 55, 150, 217, 243, 259, 262 Hepatitis, 151, 156, 262 Hepatocytes, 53, 262 Hereditary, 158, 235, 259, 262, 279, 283, 303 Heredity, 257, 262 Heritability, 28, 263 Heterodimers, 263, 268 Heterogeneity, 217, 263 Histamine, 120, 124, 136, 140, 186, 219, 234, 263, 264 Histidine, 263 Homeostasis, 11, 26, 46, 56, 121, 263, 308 Homogeneous, 239, 263 Homologous, 144, 218, 262, 263, 313 Hormonal, 5, 30, 224, 241, 263 Host, 6, 38, 41, 118, 132, 224, 225, 263, 266, 273, 319, 321 Humoral, 17, 263 Humour, 263 Hybrid, 157, 236, 263 Hybridomas, 263, 269 Hydralazine, 82, 263 Hydration, 157, 263 Hydrocortisone, 5, 48, 263 Hydrogen Cyanide, 50, 263 Hydrogen Peroxide, 14, 264, 274, 312 Hydrolysis, 118, 130, 227, 236, 250, 264, 292, 294, 298 Hydrophilic, 140, 264 Hydrophobic, 140, 264, 274 Hydroxyzine, 124, 264 Hyperalgesia, 59, 264 Hyperbilirubinemia, 264, 271 Hypercalcemia, 161, 264 Hypercapnia, 46, 105, 264 Hypercarbia, 25, 264 Hypercholesterolemia, 247, 264 Hyperglycemia, 35, 148, 151, 154, 159, 264
Index 333
Hyperhomocysteinemia, 4, 242, 264 Hyperlipidemia, 247, 264 Hyperplasia, 114, 115, 264 Hypersensitivity, 10, 16, 36, 61, 79, 218, 219, 264, 273, 278, 304 Hypersensitivity, Immediate, 218, 264 Hyperthermia, 34, 264 Hypertriglyceridemia, 247, 264 Hypertrophy, 112, 119, 130, 134, 135, 139, 140, 225, 240, 264, 317 Hyperuricemia, 259, 265 Hyperventilation, 97, 148, 185, 265 Hypesthesia, 265, 283 Hypnotic, 225, 265 Hypoglycaemia, 78, 243, 265 Hypoglycemia, 148, 154, 265 Hypoglycemic, 148, 265 Hypoglycemic Agents, 148, 265 Hypokinesia, 265, 289 Hypophysis, 265, 305 Hypotensive, 10, 17, 19, 43, 55, 57, 60, 117, 121, 131, 143, 265, 271 Hypothalamic, 5, 8, 265 Hypothalamus, 8, 224, 228, 245, 265, 293, 296, 314 Hypothermia, 80, 85, 262, 265 Hypovolaemia, 100, 265 Hypovolemia, 21, 28, 35, 74, 265 Hypoxemia, 49, 158, 265 Hypoxia, 11, 25, 28, 29, 52, 54, 58, 114, 115, 243, 265 Hysterotomy, 234, 265 I Idiopathic, 37, 58, 79, 157, 265 Illusion, 265, 321 Imaging procedures, 265, 316 Imidazole, 136, 263, 266 Immune response, 220, 221, 224, 241, 260, 266, 275, 279, 311, 319, 321 Immune Sera, 266 Immune system, 224, 226, 248, 266, 273, 275, 280, 319, 322 Immunity, 266, 269, 275, 317 Immunization, 16, 65, 194, 266 Immunoassay, 52, 266 Immunodeficiency, 119, 134, 180, 266 Immunogenic, 266, 300 Immunoglobulin, 221, 253, 266, 279 Immunohistochemistry, 18, 27, 32, 60, 266 Immunologic, 36, 235, 258, 262, 266, 301 Immunologic Factors, 262, 266 Immunology, 217, 266
Immunophilin, 229, 266 Immunosuppressive, 229, 258, 266 Impairment, 11, 34, 79, 81, 126, 164, 223, 226, 243, 247, 266, 277 Implant radiation, 266, 269, 300 Implantation, 20, 238, 266 Impotence, 125, 137, 145, 252, 266, 291 In situ, 18, 32, 43, 54, 266 In Situ Hybridization, 18, 43, 266 In vitro, 14, 15, 16, 32, 34, 51, 52, 227, 233, 249, 266, 267, 294 In vivo, 14, 15, 28, 32, 33, 34, 42, 43, 51, 52, 53, 56, 118, 266, 267, 278, 308, 314 Incision, 229, 259, 265, 267, 270, 298, 304, 314 Incontinence, 133, 138, 144, 203, 251, 267 Incubation, 267, 291 Incubation period, 267, 291 Indicative, 137, 149, 239, 267, 289, 319 Induction, 13, 22, 36, 42, 53, 65, 69, 96, 116, 220, 267, 269, 271 Infancy, 26, 267 Infarction, 54, 112, 119, 120, 130, 134, 139, 140, 148, 154, 166, 187, 188, 196, 197, 202, 226, 234, 240, 267, 270, 278, 281, 302 Infiltration, 258, 267 Inflammatory bowel disease, 156, 267 Influenza, 155, 267 Infusion, 25, 35, 46, 51, 60, 77, 83, 228, 267, 281, 317 Ingestion, 17, 56, 259, 267, 294 Inhalation, 217, 267, 271, 294 Initiation, 19, 151, 267, 316 Inlay, 267, 303 Inner ear, 237, 267, 272 Innervation, 228, 268, 276, 291, 299, 300, 305, 315, 318 Inoculum, 155, 268 Inoperable, 25, 268 Inorganic, 236, 268, 284 Inotropic, 30, 44, 113, 246, 268 Insight, 7, 54, 268 Insomnia, 137, 151, 268 Insulator, 268, 280 Insulin, 7, 9, 10, 148, 159, 186, 244, 259, 268, 271, 288, 318 Insulin-dependent diabetes mellitus, 268 Integrins, 33, 268 Intensive Care, 5, 22, 41, 44, 58, 69, 77, 96, 149, 162, 268 Intensive Care Units, 22, 41, 268 Interferon, 47, 65, 268
334
Hypotension
Interferon-alpha, 268 Interindividual, 28, 268 Interleukin-1, 18, 65, 268, 269 Interleukin-18, 18, 269 Interleukin-2, 67, 90, 269 Interleukin-3, 237, 269 Interleukin-6, 14, 269 Interleukin-8, 14, 269 Interleukins, 18, 156, 269 Intermittent, 269, 290 Internal Medicine, 38, 58, 83, 87, 100, 156, 250, 269, 282 Internal radiation, 269, 300 Interpersonal Relations, 134, 269 Interstitial, 32, 41, 129, 161, 228, 254, 269, 282, 302 Intervertebral, 245, 269, 274, 300 Intervertebral Disk Displacement, 269, 274, 300 Intestinal, 34, 36, 136, 232, 251, 259, 269, 275, 276, 320 Intestines, 215, 255, 257, 269, 276, 305 Intoxication, 243, 269, 319, 322 Intracellular, 20, 22, 41, 64, 119, 135, 230, 267, 268, 269, 277, 284, 295, 297, 301, 304, 305, 307 Intracellular Membranes, 269, 277 Intracranial Aneurysm, 234, 269, 270 Intracranial Arteriosclerosis, 234, 269 Intracranial Hypertension, 260, 270, 315 Intracranial Hypotension, 68, 70, 71, 72, 73, 74, 75, 76, 78, 83, 85, 86, 88, 89, 90, 92, 93, 94, 134, 270, 311 Intracranial Pressure, 11, 19, 41, 270 Intramuscular, 270, 288 Intraocular, 27, 141, 270, 285 Intraocular pressure, 27, 141, 270, 285 Intrathecal, 61, 83, 270 Intravascular, 11, 40, 77, 121, 128, 270 Intravenous, 30, 35, 50, 66, 77, 83, 155, 228, 267, 270, 288 Intrinsic, 7, 128, 217, 270 Intubation, 232, 270 Invasive, 11, 16, 41, 49, 86, 266, 270, 275, 287 Involuntary, 225, 235, 252, 255, 270, 281, 292, 302, 307, 308 Ion Channels, 52, 270, 284 Ionizing, 218, 251, 270, 301 Ions, 133, 225, 229, 230, 234, 246, 248, 263, 270, 295, 298 Irinotecan, 203, 270
Irritable Bowel Syndrome, 190, 270 Ischemia, 7, 20, 23, 34, 35, 44, 52, 58, 79, 156, 166, 224, 270, 281, 302 Ischemic stroke, 58, 139, 271 Isoflurane, 40, 271 Isolated limb perfusion, 47, 271 Isoproterenol, 51, 114, 271 Ixodes, 224, 271 J Jaundice, 150, 264, 271 Joint, 120, 151, 152, 167, 202, 223, 271, 286, 310, 313 K Kallidin, 228, 271 Kb, 53, 176, 271 Keratinocytes, 269, 271 Ketamine, 157, 271 Ketone Bodies, 244, 271 Ketorolac, 61, 271 Ketosis, 244, 271 Kidney Disease, 3, 96, 110, 148, 158, 176, 181, 197, 272, 302 Kidney Failure, 126, 150, 152, 251, 262, 272, 276 Kidney Failure, Acute, 272 Kidney Failure, Chronic, 272 Kidney stone, 272, 319 Kinetic, 24, 51, 270, 272 L Labile, 237, 272 Labyrinth, 267, 272, 290, 321 Labyrinthine, 63, 94, 272 Labyrinthitis, 185, 272 Laceration, 272, 314 Lactation, 272, 287 Lactose Intolerance, 272, 278 Large Intestine, 245, 251, 269, 272, 301, 307 Latency, 62, 272 Latent, 32, 39, 272, 295 Laterality, 10, 272 Lavage, 156, 157, 273 Lectin, 273, 277 Lens, 222, 273, 321 Leprosy, 256, 273 Leptin, 8, 273 Leptospirosis, 80, 84, 273 Lesion, 156, 218, 240, 256, 260, 273, 274, 318 Lethal, 46, 47, 225, 241, 273 Lethargy, 123, 124, 143, 273 Leucocyte, 218, 273 Leukemia, 180, 273
Index 335
Leukocytes, 227, 228, 235, 251, 260, 268, 269, 273, 279, 317 Leukopenia, 38, 273 Leukotrienes, 81, 120, 223, 248, 273 Levodopa, 100, 246, 273 Library Services, 210, 273 Life cycle, 216, 227, 256, 273 Ligament, 273, 297, 310 Ligands, 15, 119, 135, 137, 142, 143, 268, 273 Ligation, 23, 71, 273 Limb perfusion, 273 Lincomycin, 236, 274 Linkages, 262, 274, 313 Lipid, 222, 230, 268, 274, 280, 287 Lipid Peroxidation, 274, 287 Lipopolysaccharide, 22, 101, 259, 274 Lipoprotein, 65, 247, 259, 274 Lipoxygenase, 273, 274 Localization, 32, 40, 266, 274 Localized, 219, 243, 260, 261, 267, 274, 293, 305, 314, 318, 319 Locus Coeruleus, 42, 274 Loop, 123, 274 Lordosis, 274, 290 Low Back Pain, 133, 274 Low-density lipoprotein, 247, 274 Lumbar, 82, 269, 274, 275, 305, 315 Lumen, 34, 54, 74, 232, 250, 275 Lupus, 39, 275, 313 Lymph, 224, 234, 236, 250, 263, 275 Lymph node, 224, 234, 275 Lymphatic, 250, 267, 275, 294, 308, 309, 315 Lymphatic system, 275, 308, 309, 315 Lymphocyte, 222, 275, 276 Lymphoid, 221, 273, 275 Lymphokines, 155, 275 Lymphoma, 180, 275 Lytic, 275, 306 M Macrophage, 237, 260, 268, 275 Macrophage Colony-Stimulating Factor, 237, 275 Magnetic Resonance Imaging, 5, 49, 93, 94, 275 Major Histocompatibility Complex, 16, 275 Malabsorption, 180, 275 Malaise, 247, 275 Malignancy, 156, 157, 275
Malignant, 100, 180, 216, 222, 229, 254, 276, 282, 301 Malnutrition, 4, 217, 224, 229, 276, 280 Mammary, 240, 276 Mammogram, 229, 276, 278 Mania, 143, 276 Manic, 112, 119, 130, 135, 139, 227, 276 Manifest, 31, 38, 62, 155, 261, 276 Mannitol, 34, 276 Mastication, 276, 317 Mastocytosis, 48, 186, 276 Meat, 276, 308 Meconium, 69, 255, 276 Meconium Aspiration, 69, 276 Medial, 276, 286, 309, 315, 318 Median Nerve, 23, 232, 276 Mediate, 22, 23, 44, 46, 52, 53, 56, 63, 114, 116, 119, 120, 135, 136, 246, 276 Mediator, 48, 57, 119, 135, 246, 269, 276, 293, 306 Medicament, 144, 276 MEDLINE, 177, 179, 181, 276 Medullary, 25, 47, 276 Meiosis, 276, 313 Melanin, 8, 274, 277, 291, 318 Melanocytes, 277 Melanoma, 47, 180, 277 Membrane Glycoproteins, 277 Membrane Proteins, 114, 116, 277 Memory, 127, 134, 219, 221, 243, 277 Meningeal, 134, 277 Meninges, 233, 241, 247, 277 Menstrual Cycle, 277, 296 Mental Disorders, 110, 265, 277, 299 Mental Health, iv, 4, 110, 176, 178, 277, 299 Mental Processes, 246, 277, 299 Mental Retardation, 112, 119, 130, 135, 139, 182, 277 Mentors, 5, 277 Mesencephalic, 274, 277, 302 Mesenteric, 14, 26, 52, 60, 101, 277, 295 Mesentery, 54, 277, 290, 309 Meta-Analysis, 66, 277 Metabolic disorder, 244, 259, 277 Metabolite, 116, 138, 139, 227, 264, 278, 285 Metastasis, 278, 282 Metastatic, 203, 229, 278 Methionine, 51, 278, 297, 312 Methyltransferase, 121, 278 MI, 119, 129, 145, 213, 278
336
Hypotension
Microbe, 278, 316 Microbiology, 15, 215, 224, 278 Microcalcifications, 229, 278 Microcirculation, 27, 52, 262, 278 Microdialysis, 28, 64, 278 Microorganism, 237, 278, 289, 322 Microscopy, 54, 278 Microtubules, 278, 287 Midodrine, 22, 77, 85, 107, 108, 109, 138, 139, 164, 170, 171, 278 Milk Hypersensitivity, 36, 278 Mineralocorticoid, 256, 278 Mitochondrial Swelling, 279, 282 Mitosis, 222, 279 Modeling, 9, 247, 279 Modification, 23, 257, 279, 300 Monitor, 26, 35, 41, 70, 115, 279, 285 Monoclonal, 263, 279, 300 Monocytes, 155, 268, 269, 273, 279 Monokines, 155, 279 Mononeuropathies, 152, 279 Mononuclear, 254, 260, 275, 279, 317 Monophosphate, 10, 166, 279 Morphine, 126, 127, 279, 281, 286 Morphology, 8, 55, 279 Motility, 136, 152, 165, 279, 306 Motion Sickness, 279, 282 Motor nerve, 154, 279, 280 Movement Disorders, 279, 314 Mucilaginous, 276, 280 Mucinous, 257, 280 Mucins, 280, 304 Mucosa, 251, 257, 275, 280, 320 Multiple Organ Failure, 53, 55, 57, 280 Multiple sclerosis, 32, 280 Multiple Trauma, 5, 280 Muscle Contraction, 114, 122, 167, 219, 264, 280 Muscle Fibers, 280, 281 Muscle relaxant, 280, 282, 313 Muscle Relaxation, 230, 280, 283 Muscular Atrophy, 180, 280 Muscular Dystrophies, 247, 280 Mutagenesis, 33, 280 Mutagenic, 280, 284, 308 Mutagens, 280 Myalgia, 155, 267, 280 Myasthenia, 280, 282 Mydriatic, 245, 280, 292 Myelin, 280, 306 Myelography, 72, 280 Myelosuppression, 119, 134, 280
Myocardial Ischemia, 8, 23, 142, 220, 240, 281 Myocardial Reperfusion, 281, 302 Myocardial Reperfusion Injury, 281, 302 Myocarditis, 38, 281 Myocardium, 7, 20, 54, 220, 278, 281 Myosin, 14, 229, 280, 281 Myotonic Dystrophy, 180, 281 N Narcolepsy, 137, 199, 251, 281 Narcosis, 281 Narcotic, 123, 124, 126, 127, 154, 279, 281 Nasal Mucosa, 267, 281 Nasogastric, 156, 281 Natriuresis, 10, 220, 281 Nausea, 25, 69, 150, 158, 186, 190, 191, 218, 221, 257, 272, 282, 288, 318 NCI, 1, 110, 175, 236, 282 Necrosis, 5, 39, 157, 222, 234, 254, 267, 278, 281, 282, 302 Neonatal, 12, 77, 80, 90, 148, 191, 192, 194, 282 Neoplasia, 180, 282 Neoplasms, 222, 228, 231, 282, 301 Neoplastic, 254, 263, 275, 282, 304 Neostigmine, 61, 282 Nephritis, 161, 282 Nephrologist, 151, 282 Nephrology, 24, 70, 72, 77, 115, 156, 157, 161, 162, 282 Nephropathy, 148, 158, 161, 272, 282 Nerve Endings, 23, 27, 114, 260, 282 Nerve Fibers, 154, 228, 282, 309, 315 Nervous System, 17, 18, 24, 27, 56, 105, 108, 123, 133, 136, 143, 150, 154, 180, 215, 217, 224, 225, 228, 229, 230, 233, 247, 251, 253, 256, 273, 276, 279, 280, 282, 283, 284, 286, 290, 292, 294, 306, 312, 313 Networks, 17, 46, 282 Neural, 9, 23, 24, 28, 31, 32, 35, 46, 56, 70, 217, 219, 263, 282 Neural Pathways, 32, 282 Neuralgia, 126, 128, 133, 167, 283 Neuritis, 185, 283, 321 Neuroanatomy, 157, 283 Neurodegenerative Diseases, 126, 127, 135, 139, 225, 283 Neuroeffector Junction, 282, 283 Neuroendocrine, 5, 283 Neuroendocrinology, 5, 283
Index 337
Neurogenic, 56, 67, 72, 73, 86, 88, 100, 107, 108, 109, 157, 283, 319 Neurologic, 58, 64, 89, 134, 158, 283 Neurologist, 93, 283 Neuroma, 185, 283 Neuromuscular, 192, 215, 254, 283, 317, 318 Neuromuscular Blockade, 192, 283 Neuromuscular Junction, 215, 283 Neuronal, 23, 43, 47, 56, 59, 64, 230, 281, 283 Neuropathy, 4, 26, 40, 151, 152, 153, 154, 186, 224, 283, 290 Neurophysiology, 157, 244, 283 Neurosis, 283, 292 Neurosurgeon, 93, 283 Neurotoxic, 64, 284 Neurotoxicity, 25, 61, 284 Neurotransmitters, 29, 137, 140, 279, 284, 296, 308 Neutrons, 218, 284, 300 Neutropenia, 38, 119, 134, 284 Neutrophil, 33, 38, 284 Nimodipine, 64, 284 Nitrates, 60, 166, 284 Nitric acid, 284 Nitric Oxide, 10, 34, 42, 44, 46, 53, 55, 60, 65, 81, 90, 101, 115, 116, 119, 120, 165, 166, 284 Nitrogen, 51, 116, 126, 142, 218, 220, 263, 272, 284, 317 Nitrogen Oxides, 51, 284 Nitroglycerin, 116, 166, 284 Nitroprusside, 77, 80, 284 Nitrosamines, 284, 308 Non-small cell lung cancer, 25, 284 Normotensive, 43, 285 Nortriptyline, 66, 285 Nuclear, 53, 92, 200, 218, 225, 230, 236, 248, 253, 256, 282, 285, 303 Nuclei, 63, 218, 248, 253, 254, 257, 275, 279, 284, 285, 286, 298, 321 Nucleic acid, 266, 280, 284, 285, 300 Nursing Care, 285, 289 Nutritional Status, 24, 285 Nystagmus, 248, 272, 285 O Obtundation, 83, 285 Octanes, 142, 285 Ocular, 27, 63, 142, 143, 148, 256, 285 Ocular Hypotension, 27, 142, 285 Odour, 223, 285, 318
Oliguria, 272, 276, 285 Omentum, 54, 285 Oncogene, 180, 285 Oncogenic, 268, 285, 298, 299 On-line, 41, 213, 285 Opacity, 243, 285 Ophthalmic, 73, 285 Opioid Peptides, 19, 145, 247, 250, 251, 285 Opium, 279, 286 Opportunistic Infections, 38, 286 Opsin, 286, 303 Optic Chiasm, 265, 286 Optic Disk, 239, 244, 286 Optic Nerve, 286, 303 Oral Health, 149, 286 Organelles, 233, 242, 277, 279, 286 Orofacial, 254, 286 Osmolarity, 276, 286 Osmosis, 286 Osmotic, 11, 30, 117, 217, 279, 286, 307 Osteoarthritis, 118, 133, 134, 286 Osteoporosis, 39, 112, 118, 130, 131, 134, 139, 140, 286 Outpatient, 134, 286 Ovary, 240, 252, 287 Overactive bladder, 129, 287 Overdose, 148, 154, 287 Ovum, 240, 243, 258, 273, 287, 296 Oxidation, 51, 215, 222, 227, 242, 244, 246, 274, 287 Oxidative metabolism, 273, 287 Oxidative Stress, 14, 26, 55, 287 Oxides, 284, 287 Oximetry, 49, 287 Oxygen Consumption, 8, 253, 287, 303 Oxygenase, 55, 287 Oxygenation, 40, 100, 157, 265, 287 Oxygenator, 231, 287 Oxytocin, 35, 287 P Pacemaker, 287 Paclitaxel, 25, 287 Paediatric, 74, 203, 287 Pain, Postoperative, 126, 128, 133, 288 Palate, 258, 288, 319 Palliative, 288, 314 Palsy, 92, 218, 288 Pancreas, 38, 215, 245, 268, 288, 309 Pancreas Transplant, 38, 288 Pancreatic, 77, 180, 232, 288 Pancreatic cancer, 180, 288 Pancreatitis, 77, 288
338
Hypotension
Panic, 196, 288, 306 Panic Disorder, 196, 288, 306 Paralysis, 254, 277, 288, 299, 309 Parenchyma, 49, 288 Parenteral, 45, 251, 288 Paresis, 254, 261, 283, 288 Paresthesias, 283, 288 Parkinsonism, 91, 126, 127, 164, 273, 289 Paroxetine, 65, 289 Paroxysmal, 180, 185, 220, 261, 289, 291, 320, 322 Particle, 289, 308, 317 Patch, 27, 52, 70, 78, 93, 239, 289 Pathogen, 267, 268, 289 Pathogenesis, 13, 26, 32, 46, 50, 57, 150, 153, 161, 289 Pathologic, 10, 14, 25, 215, 222, 226, 240, 264, 289, 299 Pathologic Processes, 14, 222, 289 Pathologies, 54, 119, 136, 185, 289 Pathophysiology, 10, 11, 16, 26, 41, 49, 55, 60, 88, 89, 136, 150, 157, 159, 289 Patient Education, 151, 185, 208, 210, 213, 289 Pediatric Nursing, 157, 289 Pelvic, 21, 199, 289, 297 Penicillin, 155, 197, 221, 289 Penile Erection, 125, 145, 289 Penis, 125, 145, 157, 166, 289, 296 Pepsin, 289 Peptic, 151, 156, 289 Peptic Ulcer, 151, 156, 289 Peptide, 15, 33, 118, 126, 127, 144, 239, 273, 286, 289, 293, 294, 297, 298, 312 Peptide T, 15, 289 Perception, 20, 152, 244, 289, 305 Percutaneous, 4, 84, 157, 246, 289 Perforation, 256, 290, 316 Perfusion, 14, 19, 26, 27, 29, 34, 46, 58, 187, 200, 265, 290, 315 Periaqueductal Gray, 17, 23, 290 Pericarditis, 152, 290 Pericardium, 290, 313 Perilymph, 185, 290 Perineal, 290, 300 Periodontal disease, 23, 290 Perioperative, 88, 155, 189, 290 Peripheral Nervous System, 152, 154, 251, 261, 283, 288, 290, 296, 311, 320 Peripheral Neuropathy, 156, 186, 290 Peripheral Vascular Disease, 148, 290, 291
Peritoneal, 4, 69, 80, 151, 155, 158, 223, 245, 290 Peritoneal Cavity, 151, 223, 290 Peritoneal Dialysis, 4, 69, 80, 151, 158, 245, 290 Peritoneum, 277, 285, 290 Peritonitis, 33, 151, 290 Perivascular, 29, 120, 291 Peroneal Nerve, 154, 291, 305 Pertussis, 15, 291, 322 PH, 67, 81, 114, 116, 153, 200, 291 Phagocytosis, 16, 291 Pharmacodynamic, 45, 291 Pharmacokinetic, 291 Pharmacologic, 18, 23, 30, 45, 49, 51, 61, 159, 191, 198, 220, 260, 291, 315, 316, 319 Pharmacotherapy, 22, 51, 291 Pharyngitis, 291, 304 Pharynx, 265, 267, 291, 319 Phenotype, 28, 33, 56, 112, 140, 291 Phenoxybenzamine, 97, 291 Phentolamine, 44, 291 Phenyl, 141, 142, 291 Phenylalanine, 291, 318 Phenylephrine, 14, 51, 60, 121, 292 Phobia, 74, 292 Phobic Disorders, 292 Phosphodiesterase, 55, 118, 130, 132, 140, 166, 292 Phospholipases, 292, 307 Phospholipids, 254, 274, 292 Phosphorus, 121, 151, 230, 292 Phosphorylated, 33, 237, 292 Phosphorylation, 14, 32, 119, 135, 292 Photocoagulation, 236, 292 Physical Examination, 158, 258, 292 Physostigmine, 157, 282, 292 Pigment, 226, 277, 292 Piloerection, 265, 292 Pilot study, 45, 48, 58, 292 Pituitary Gland, 241, 292, 296 Placenta, 25, 31, 252, 255, 293, 296, 318 Plants, 215, 218, 224, 225, 231, 234, 236, 258, 273, 279, 285, 293, 304, 310, 316 Plaque, 220, 223, 293 Plasma cells, 221, 293 Plasma expander, 46, 293 Plasma protein, 30, 117, 131, 217, 250, 293, 298, 307 Plasma Volume, 10, 28, 30, 50, 152, 227, 278, 293 Plasticity, 63, 293
Index 339
Platelet Activation, 293, 307 Platelet Aggregation, 219, 284, 293, 314 Platelet Factor 4, 269, 293 Platelet-Derived Growth Factor, 14, 293 Platelets, 226, 281, 284, 293, 314 Platinum, 236, 274, 293 Plethysmograph, 41, 294 Plethysmography, 21, 41, 294 Plexus, 228, 294, 305 Pneumothorax, 276, 294 Poisoning, 50, 121, 234, 243, 257, 269, 282, 294, 306, 308 Polycystic, 158, 181, 294 Polyethylene, 47, 294 Polymerase, 33, 294 Polymerase Chain Reaction, 33, 294 Polymorphic, 112, 294 Polymorphism, 66, 294 Polypeptide, 118, 119, 131, 132, 135, 139, 218, 237, 255, 294, 298, 320, 322 Polyradiculopathy, 152, 294 Polysaccharide, 221, 294 Polyuria, 126, 127, 294 Pons, 218, 229, 254, 256, 294, 303, 304 Popliteal, 122, 295 Portal Vein, 34, 295 Posterior, 63, 91, 219, 223, 233, 235, 246, 258, 287, 288, 295, 300, 309, 319 Postmenopausal, 286, 295 Postnatal, 59, 295, 310 Postoperative, 19, 61, 69, 83, 155, 191, 280, 295 Postprandial, 6, 12, 83, 89, 95, 100, 101, 295 Postsynaptic, 64, 283, 295, 307, 313 Post-synaptic, 23, 295 Post-translational, 22, 295 Post-traumatic, 5, 261, 280, 295 Potassium, 9, 11, 29, 145, 217, 278, 295 Potassium Channels, 29, 295 Potentiate, 124, 295 Potentiation, 295, 307 Practice Guidelines, 178, 187, 188, 189, 192, 197, 200, 203, 295 Precipitating Factors, 185, 232, 261, 295 Preclinical, 25, 47, 61, 109, 295 Precursor, 86, 120, 220, 223, 246, 248, 250, 251, 259, 273, 285, 291, 295, 296, 298, 317, 318 Predisposition, 73, 295 Prednisolone, 295, 296 Prednisone, 39, 296 Preeclampsia, 88, 296
Pregnancy in Diabetics, 244, 296 Pregnancy Outcome, 83, 296 Prenatal, 25, 249, 296 Pressoreceptors, 225, 296 Presynaptic, 64, 282, 283, 296, 313 Presynaptic Terminals, 282, 296 Prevalence, 23, 89, 125, 145, 151, 296 Priapism, 157, 296 Probe, 24, 49, 278, 296 Proctocolitis, 36, 296 Progesterone, 30, 296, 310 Progression, 221, 296 Progressive, 12, 155, 233, 235, 243, 247, 260, 272, 280, 281, 282, 283, 286, 293, 296, 302, 317 Projection, 57, 243, 285, 286, 296, 302 Promoter, 53, 55, 296 Prone, 70, 71, 72, 84, 91, 147, 296 Prone Position, 91, 147, 296 Pro-Opiomelanocortin, 250, 286, 296 Prophase, 297, 313 Prophylaxis, 48, 119, 297, 319 Proportional, 64, 297 Prospective Studies, 36, 297 Prospective study, 39, 74, 90, 297 Prostaglandin, 11, 48, 100, 101, 186, 220, 241, 297, 314 Prostaglandin-Endoperoxide Synthase, 241, 297 Prostaglandins A, 297 Prostate, 180, 225, 297, 298, 300, 304 Prostate gland, 297, 298 Prostatectomy, 298, 300 Prostatic Hyperplasia, 114, 115, 153, 298 Protease, 16, 237, 298 Protective Agents, 230, 298 Protein Binding, 298, 315 Protein C, 18, 36, 37, 117, 118, 130, 132, 140, 156, 217, 218, 222, 225, 274, 298, 318 Protein Conformation, 218, 298 Protein Kinases, 118, 298 Protein S, 20, 24, 118, 119, 130, 135, 141, 181, 227, 298 Proteinuria, 296, 298 Proteolytic, 218, 238, 255, 298 Prothrombin, 298, 314 Protocol, 9, 39, 298 Protons, 218, 263, 270, 298, 300 Proto-Oncogene Proteins, 287, 298 Proto-Oncogene Proteins c-mos, 287, 298 Protozoa, 278, 299, 310 Proximal, 62, 246, 296, 299
340
Hypotension
Pruritic, 248, 299 Pruritus, 156, 264, 299, 318 Psoriasis, 118, 119, 134, 299 Psychiatric, 33, 35, 137, 198, 277, 299 Psychiatry, 35, 67, 76, 82, 94, 199, 299, 311, 320 Psychic, 157, 283, 299, 305 Psychogenic, 166, 299, 319 Psychology, 50, 56, 246, 299 Psychomotor, 243, 299 Ptosis, 28, 299 Public Health, 17, 23, 37, 84, 158, 178, 299 Public Policy, 177, 299 Publishing, 64, 299 Pulmonary Artery, 55, 227, 299, 320 Pulmonary Edema, 148, 154, 272, 299 Pulmonary Embolism, 84, 122, 195, 299 Pulmonary hypertension, 55, 69, 240, 299 Pulmonary Ventilation, 265, 299, 303 Pulse, 53, 279, 287, 300 Pupil, 240, 245, 280, 300 Purifying, 20, 300 Purines, 300, 306 Putrefaction, 257, 300 Pyrogenic, 16, 155, 300 Q Quality of Life, 62, 109, 153, 156, 300 R Radial Artery, 79, 300 Radial Nerve, 154, 300 Radiation, 25, 105, 157, 191, 218, 220, 224, 251, 253, 256, 264, 269, 270, 300, 301, 304, 322 Radiation therapy, 25, 157, 191, 253, 269, 300, 304 Radical prostatectomy, 77, 300 Radicular, 300 Radiculopathy, 154, 300 Radioactive, 224, 260, 263, 266, 269, 285, 300, 301 Radioimmunoassay, 27, 226, 300 Radioimmunotherapy, 301 Radioisotope, 252, 301, 316 Radiolabeled, 300, 301 Radiological, 290, 301 Radiopharmaceuticals, 200, 301 Radiotherapy, 25, 187, 228, 300, 301 Radius, 300, 301 Rage, 290, 301 Randomized, 5, 44, 48, 50, 62, 67, 71, 90, 248, 301 Reactive Oxygen Species, 34, 301
Reagent, 253, 301, 308 Receptors, Serotonin, 301, 306 Recombinant, 18, 32, 51, 101, 112, 118, 130, 131, 134, 139, 301, 320 Rectal, 157, 301 Rectum, 222, 228, 237, 245, 255, 257, 267, 272, 296, 297, 301 Recurrence, 227, 301 Red blood cells, 57, 156, 158, 252, 262, 281, 287, 301, 304 Red Nucleus, 223, 301 Reductase, 115, 302 Refer, 1, 127, 237, 246, 250, 256, 262, 274, 284, 301, 302, 321 Reflex, 9, 21, 23, 31, 36, 76, 187, 290, 302 Refraction, 302, 309 Refractory, 13, 29, 41, 44, 55, 78, 85, 89, 95, 248, 302 Regimen, 54, 109, 143, 248, 291, 302 Relapse, 124, 302 Remission, 227, 301, 302 Renal Artery, 60, 161, 302 Renal Dialysis, 41, 302 Renal failure, 80, 120, 156, 226, 243, 302 Renal Osteodystrophy, 151, 302 Renin, 17, 30, 36, 90, 95, 150, 220, 302 Renin-Angiotensin System, 95, 220, 302 Renovascular, 84, 302 Reperfusion, 8, 19, 44, 52, 281, 302 Reperfusion Injury, 44, 302 Reproduction Techniques, 296, 302 Respiration, 51, 113, 222, 231, 234, 279, 287, 302, 303 Respiratory Burst, 38, 303 Respiratory System, 217, 303, 320 Restoration, 56, 113, 116, 281, 302, 303, 322 Resuscitation, 44, 46, 77, 83, 113, 156, 231, 303 Reticular, 47, 303 Reticular Formation, 47, 303 Retina, 27, 235, 236, 238, 239, 244, 248, 273, 286, 303, 304, 306, 319, 321 Retinal, 27, 228, 244, 286, 303 Retinal Ganglion Cells, 27, 286, 303 Retinoblastoma, 180, 303 Retinol, 303 Retinopathy, 75, 151, 244, 303 Retrograde, 19, 303 Retropubic, 298, 300, 303, 304 Retropubic prostatectomy, 300, 304 Rheology, 54, 304 Rheumatism, 126, 128, 304
Index 341
Rheumatoid, 118, 119, 133, 134, 237, 304 Rheumatoid arthritis, 118, 119, 134, 237, 304 Rhinitis, 229, 234, 251, 278, 304 Rhombencephalon, 256, 304 Ribonuclease, 64, 304 Ribose, 216, 304 Rickettsiae, 304 Rigidity, 270, 289, 293, 304 Risk factor, 38, 40, 69, 81, 96, 120, 150, 159, 233, 264, 297, 304 Rod, 225, 236, 250, 304 S Saline, 77, 83, 90, 304 Saliva, 50, 304 Salivary, 242, 245, 288, 304 Salivary glands, 242, 245, 304 Salvage Therapy, 25, 304 Saphenous, 240, 304 Saphenous Vein, 240, 304 Saponins, 304, 310 Scarlet Fever, 16, 304 Schizoid, 304, 322 Schizophrenia, 27, 112, 119, 126, 127, 130, 135, 136, 139, 199, 201, 305, 322 Schizotypal Personality Disorder, 244, 305, 322 Sciatic Nerve, 52, 291, 305, 315 Scleroderma, 254, 305 Sclerosis, 139, 180, 237, 270, 280, 305 Scoliosis, 91, 305 Screening, 61, 112, 132, 135, 185, 236, 305 Second Messenger Systems, 284, 305 Secretion, 32, 33, 35, 59, 216, 241, 263, 268, 269, 272, 278, 280, 305 Sedative, 154, 225, 264, 305 Sedentary, 6, 7, 305 Segmental, 47, 305, 309 Segmentation, 305 Seizures, 10, 52, 58, 135, 147, 158, 243, 289, 305 Selection Bias, 26, 305 Sella, 5, 246, 292, 305 Semen, 297, 305 Semisynthetic, 230, 236, 305 Senile, 144, 286, 306 Sensibility, 219, 264, 306 Sensor, 137, 306 Sensory loss, 300, 306, 314 Sepsis, 13, 29, 41, 53, 57, 116, 306 Septicemia, 57, 306 Sequence Analysis, 33, 306
Sequence Homology, 289, 306 Sequencing, 20, 294, 306 Serine, 119, 135, 242, 299, 306 Serologic, 39, 266, 306 Serotonin, 56, 124, 137, 140, 167, 216, 229, 289, 291, 301, 306, 317 Serotonin Uptake Inhibitors, 167, 306 Serous, 250, 306 Serrata, 236, 306 Sertraline, 76, 306 Sertraline Hydrochloride, 76, 306 Serum, 5, 45, 65, 217, 219, 226, 237, 246, 266, 272, 274, 278, 291, 301, 306, 307, 317 Serum Albumin, 301, 307 Sex Characteristics, 216, 220, 307, 314 Sex Determination, 181, 307 Shivering, 58, 307 Signal Transduction, 14, 15, 27, 52, 53, 118, 119, 130, 132, 135, 140, 229, 307 Signs and Symptoms, 150, 155, 302, 307, 318 Skeletal, 7, 9, 14, 60, 133, 220, 236, 271, 280, 307, 308 Skeleton, 215, 271, 297, 307 Skull, 241, 270, 307, 313 Sleep apnea, 4, 307 Small cell lung cancer, 307 Small intestine, 235, 247, 251, 263, 269, 281, 307 Sneezing, 291, 308 Social Environment, 300, 308 Social Isolation, 39, 305, 308 Sodium, 11, 24, 50, 56, 72, 77, 80, 184, 217, 259, 278, 281, 308, 312 Sodium Nitrite, 50, 308 Soft tissue, 155, 228, 254, 255, 307, 308 Solid tumor, 25, 220, 308 Solitary Nucleus, 224, 308 Solvent, 51, 225, 252, 286, 308 Soma, 86, 308 Somatic, 23, 135, 152, 216, 258, 263, 277, 279, 290, 308, 319 Somatic cells, 135, 277, 279, 308 Sorbitol, 276, 308 Sound wave, 238, 308 Space Flight, 41, 58, 308 Spasm, 239, 277, 308, 309 Spasmodic, 229, 291, 309 Spasmogenic, 124, 219, 309 Spastic, 270, 309 Spasticity, 20, 166, 309 Spatial disorientation, 246, 309
342
Hypotension
Specialist, 151, 205, 245, 309 Specificity, 21, 49, 217, 230, 309, 315 Spectrum, 36, 50, 309 Sphenoid, 305, 309 Spinal Cord Injuries, 300, 309 Spinal Nerve Roots, 294, 300, 309 Spinal Nerves, 290, 309 Spleen, 136, 219, 242, 275, 309 Splenic Vein, 295, 309 Spontaneous Abortion, 296, 309 Sporadic, 10, 12, 283, 303, 309 Spores, 268, 310 Sprains and Strains, 274, 310 Squamous, 284, 310 Squamous cell carcinoma, 284, 310 Stabilization, 7, 199, 310 Standard therapy, 30, 120, 310 Statistically significant, 41, 310 Steady state, 49, 310 Steel, 236, 310, 319 Stellate, 24, 310 Stellate Ganglion, 24, 310 Stem Cells, 252, 310 Stent, 81, 310 Steroid, 60, 78, 120, 241, 304, 310 Stillbirth, 26, 296, 310 Stimulant, 123, 143, 263, 271, 310, 313 Stimulus, 35, 55, 115, 239, 247, 248, 253, 268, 269, 270, 272, 288, 292, 302, 310, 314 Stomach Ulcer, 165, 311 Stool, 267, 270, 272, 311 Strand, 294, 311 Streptococcal, 16, 86, 155, 274, 311 Streptococci, 304, 311 Streptococcus, 155, 254, 311 Stroke, 35, 39, 49, 52, 58, 76, 81, 88, 110, 120, 133, 139, 148, 154, 176, 184, 185, 231, 271, 311 Stroke Volume, 58, 231, 311 Stroma, 288, 311 Stupor, 273, 281, 311 Subacute, 267, 311 Subarachnoid, 58, 91, 118, 131, 256, 260, 311 Subclinical, 39, 267, 305, 311 Subcutaneous, 216, 248, 288, 311 Subdural Effusion, 70, 311 Subspecies, 309, 311 Substance P, 278, 305, 311 Substrate, 241, 251, 311 Suction, 255, 311 Sudden cardiac death, 20, 311
Sudden death, 20, 25, 311 Sulfur, 142, 278, 312 Sulfuric acid, 50, 312 Superantigens, 16, 155, 312 Superoxide, 29, 38, 44, 67, 143, 303, 312 Superoxide Dismutase, 67, 143, 312 Supine, 12, 21, 26, 51, 69, 80, 137, 138, 152, 312 Supine Position, 80, 137, 312 Supplementation, 29, 312 Suppression, 8, 53, 241, 312 Supraspinal, 59, 312 Survival Rate, 143, 312 Suspensions, 50, 312 Sweat, 154, 265, 312 Sweat Glands, 312 Sympathetic Nervous System, 6, 7, 28, 33, 114, 116, 136, 150, 220, 224, 312 Sympatholytics, 120, 312 Sympathomimetic, 129, 157, 216, 246, 252, 271, 285, 312 Symphysis, 297, 313 Symptomatic, 17, 107, 108, 153, 154, 244, 288, 296, 313 Synapses, 283, 284, 313 Synapsis, 313 Synaptic, 47, 60, 306, 307, 313 Syncope, 7, 12, 16, 56, 74, 75, 89, 97, 137, 147, 154, 195, 313 Synergistic, 25, 313 Systemic lupus erythematosus, 161, 237, 313 Systolic, 39, 55, 81, 85, 109, 121, 137, 152, 193, 196, 264, 313 Systolic blood pressure, 55, 85, 109, 137, 313 T Tachycardia, 7, 20, 21, 60, 75, 81, 255, 313 Tachypnea, 276, 313 Tacrine, 96, 313 Teichoic Acids, 259, 313 Telangiectasia, 181, 313 Temporal, 185, 261, 313 Terbutaline, 157, 313 Testicular, 119, 134, 313 Testis, 252, 313 Testosterone, 302, 314 Tetani, 314 Tetanic, 314 Tetanus, 36, 314 Thalamic, 223, 314 Thalamic Diseases, 223, 314
Index 343
Therapeutics, 37, 56, 170, 314 Thermal, 246, 284, 294, 314 Third Ventricle, 265, 314 Thoracic, 21, 67, 81, 82, 85, 93, 97, 128, 228, 276, 300, 310, 314, 318, 322 Thoracotomy, 20, 314 Thorax, 215, 275, 314, 319 Threonine, 119, 135, 289, 299, 306, 314 Threshold, 30, 133, 264, 314 Thrombin, 32, 140, 255, 293, 298, 314 Thrombocytopenia, 38, 78, 314 Thrombomodulin, 32, 298, 314 Thrombosis, 39, 122, 151, 226, 268, 270, 298, 311, 314 Thromboxanes, 223, 241, 248, 314 Thrombus, 84, 157, 240, 267, 271, 281, 293, 314 Thymus, 266, 275, 315 Thyroid, 148, 156, 315, 318 Thyroid Gland, 148, 315 Thyroid Hormones, 315, 318 Thyroxine, 217, 291, 315 Tibial Nerve, 122, 305, 315 Tick-Borne Diseases, 224, 315 Tidal Volume, 265, 315 Tin, 232, 290, 293, 315 Tinnitus, 88, 144, 315, 321 Tissue Distribution, 15, 315 Tissue Survival, 46, 315 Tolerance, 30, 36, 50, 58, 62, 96, 126, 127, 215, 259, 315 Tomography, 315 Tonicity, 262, 270, 315 Tonsillitis, 304, 316 Tonus, 290, 316 Tooth Preparation, 215, 316 Topical, 79, 252, 264, 316 Topoisomerase inhibitors, 270, 316 Torsion, 267, 316 Tourniquet, 74, 271, 274, 316 Toxaemia, 296, 316 Toxic, iv, 16, 25, 44, 155, 203, 224, 225, 241, 242, 251, 253, 262, 263, 266, 283, 284, 308, 316 Toxicity, 25, 27, 47, 118, 132, 154, 247, 292, 316 Toxicokinetics, 316 Toxicology, 20, 27, 100, 178, 316 Toxins, 16, 117, 131, 157, 221, 230, 249, 262, 267, 301, 306, 316 Toxoid, 16, 36, 316 Trabecular Meshwork, 316
Trabeculectomy, 143, 316 Trace element, 156, 235, 236, 256, 315, 316 Tracer, 41, 316 Trachea, 229, 291, 315, 316 Traction, 236, 316 Tractus, 12, 32, 35, 43, 46, 316 Transcription Factors, 42, 316 Transcutaneous, 122, 316 Transduction, 14, 118, 119, 130, 135, 141, 307, 317 Transfection, 33, 53, 226, 317 Transfer Factor, 266, 317 Transfusion, 46, 156, 253, 317 Translational, 53, 317 Transmitter, 215, 246, 270, 276, 285, 313, 317 Transplantation, 4, 23, 37, 72, 155, 158, 235, 249, 266, 272, 275, 317 Tremor, 277, 289, 317 Tricuspid Atresia, 240, 317 Trigeminal, 167, 254, 317 Trophic, 37, 317 Tryptophan, 237, 306, 317 Tuberous Sclerosis, 181, 317 Tubocurarine, 282, 317 Tumor Necrosis Factor, 14, 47, 65, 317 Tumour, 257, 317 Tunica Intima, 249, 317 Type 2 diabetes, 151, 318 Tyrosine, 42, 246, 318 U Ulcer, 311, 318, 319 Ulceration, 289, 318 Ulnar Nerve, 154, 318 Ultrafiltration, 19, 70, 117, 131, 158, 262, 318 Ultrasonography, 21, 258, 318 Umbilical Arteries, 318 Umbilical Cord, 40, 318 Unconscious, 220, 224, 243, 265, 318 Unresectable, 25, 318 Uraemia, 288, 318 Urea, 272, 312, 318 Uremia, 3, 152, 155, 272, 302, 318 Ureters, 272, 302, 318, 319 Urethra, 141, 225, 289, 297, 318, 319 Urge urinary incontinence, 200, 318 Uric, 151, 259, 265, 300, 319 Urinary Retention, 112, 119, 130, 134, 139, 140, 319 Urinary tract, 141, 153, 157, 319 Urinate, 319
344
Hypotension
Urogenital, 133, 258, 319 Urticaria, 36, 186, 219, 234, 264, 319 Uterine Contraction, 287, 319 Uterus, 234, 240, 243, 265, 296, 319 Uveitis, 285, 319 Uvula, 63, 319 V Vaccination, 201, 319 Vaccine, 298, 319 Vagal, 7, 10, 19, 20, 21, 31, 319 Vagina, 234, 265, 319 Vaginal, 16, 319 Vagus Nerve, 308, 319 Vanadium, 64, 319 Varicose, 122, 319 Varicose vein, 122, 319 Vascular endothelial growth factor, 14, 319 Vascular Headaches, 167, 319 Vascular Resistance, 29, 30, 41, 116, 225, 320 Vasculitis, 288, 320 Vasoactive, 9, 26, 29, 41, 156, 320 Vasoactive Intestinal Peptide, 26, 320 Vasoconstriction, 7, 9, 21, 30, 32, 150, 252, 320 Vasodilatation, 28, 57, 232, 271, 320 Vasodilation, 6, 10, 17, 41, 44, 52, 53, 54, 56, 125, 218, 220, 255, 320 Vasodilator, 22, 29, 30, 44, 48, 54, 115, 120, 228, 246, 263, 281, 284, 291, 320 Vasogenic, 11, 320 Vasomotor, 9, 12, 14, 19, 320 Vasopressor, 5, 30, 41, 100, 320 Vector, 33, 317, 320 Vein, 79, 122, 220, 223, 270, 285, 295, 304, 309, 318, 320 Venous, 17, 21, 41, 49, 113, 122, 131, 151, 223, 226, 227, 234, 243, 284, 298, 317, 320 Venous blood, 49, 113, 131, 227, 234, 320 Venous Pressure, 21, 320 Ventilation, 113, 231, 320 Ventral, 13, 23, 265, 294, 309, 320 Ventricle, 13, 223, 240, 299, 300, 313, 317, 320 Ventricular, 13, 51, 54, 113, 128, 139, 152, 193, 196, 240, 281, 317, 320, 321 Ventricular Dysfunction, 14, 320 Ventricular fibrillation, 113, 321
Ventricular Function, 54, 152, 321 Venules, 54, 227, 230, 250, 278, 321 Vertebrae, 269, 309, 321 Vertebral, 187, 252, 321 Vertigo, 185, 187, 218, 321 Vestibular, 10, 63, 185, 186, 187, 272, 321 Vestibule, 267, 321 Vestibulocochlear Nerve, 315, 321 Vestibulocochlear Nerve Diseases, 315, 321 Veterinary Medicine, 177, 321 Viral, 112, 118, 130, 134, 139, 140, 249, 267, 285, 315, 317, 321 Virulence, 224, 316, 321 Virus, 225, 233, 251, 257, 259, 268, 293, 317, 321 Viscera, 277, 308, 321 Visceral, 23, 56, 59, 121, 224, 258, 290, 319, 321 Visceral Afferents, 224, 258, 319, 321 Viscosity, 46, 227, 304, 321 Vitreous Body, 303, 321, 322 Vitreous Hemorrhage, 244, 322 Vitro, 14, 322 Vivo, 322 W Wakefulness, 243, 322 Weight Gain, 151, 322 Weight-Bearing, 152, 322 Wheezing, 278, 322 White blood cell, 54, 186, 215, 221, 251, 260, 273, 275, 281, 284, 293, 322 Whooping Cough, 291, 322 Windpipe, 291, 315, 322 Withdrawal, 19, 21, 56, 59, 60, 88, 123, 124, 243, 291, 322 Wound Healing, 139, 268, 322 X Xenograft, 221, 322 X-ray, 232, 238, 256, 276, 280, 285, 300, 301, 322 Y Yeasts, 256, 291, 322 Z Zoonoses, 224, 322 Zymogen, 298, 322
