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

GLUCOSE

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

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

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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright 2004 by ICON Group International, Inc. Copyright 2004 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1

Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Glucose Intolerance: 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: 0-497-00486-0 1. Glucose Intolerance-Popular works.I. Title.

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Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors, or authors. ICON Group International, Inc., the editors, and the authors are not responsible for the content of any Web pages or publications referenced in this publication.

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

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Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on glucose intolerance. 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 GLUCOSE INTOLERANCE .......................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Glucose Intolerance....................................................................... 8 E-Journals: PubMed Central ....................................................................................................... 47 The National Library of Medicine: PubMed ................................................................................ 48 CHAPTER 2. NUTRITION AND GLUCOSE INTOLERANCE ................................................................ 93 Overview...................................................................................................................................... 93 Finding Nutrition Studies on Glucose Intolerance...................................................................... 93 Federal Resources on Nutrition ................................................................................................... 95 Additional Web Resources ........................................................................................................... 96 CHAPTER 3. ALTERNATIVE MEDICINE AND GLUCOSE INTOLERANCE .......................................... 97 Overview...................................................................................................................................... 97 National Center for Complementary and Alternative Medicine.................................................. 97 Additional Web Resources ......................................................................................................... 104 General References ..................................................................................................................... 104 CHAPTER 4. PATENTS ON GLUCOSE INTOLERANCE ..................................................................... 107 Overview.................................................................................................................................... 107 Patents on Glucose Intolerance.................................................................................................. 107 Patent Applications on Glucose Intolerance .............................................................................. 110 Keeping Current ........................................................................................................................ 111 CHAPTER 5. BOOKS ON GLUCOSE INTOLERANCE ........................................................................ 113 Overview.................................................................................................................................... 113 Book Summaries: Federal Agencies............................................................................................ 113 Chapters on Glucose Intolerance................................................................................................ 115 CHAPTER 6. MULTIMEDIA ON GLUCOSE INTOLERANCE .............................................................. 123 Overview.................................................................................................................................... 123 Video Recordings ....................................................................................................................... 123 CHAPTER 7. PERIODICALS AND NEWS ON GLUCOSE INTOLERANCE ........................................... 125 Overview.................................................................................................................................... 125 News Services and Press Releases.............................................................................................. 125 Academic Periodicals covering Glucose Intolerance .................................................................. 127 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 131 Overview.................................................................................................................................... 131 NIH Guidelines.......................................................................................................................... 131 NIH Databases........................................................................................................................... 133 Other Commercial Databases..................................................................................................... 135 APPENDIX B. PATIENT RESOURCES ............................................................................................... 137 Overview.................................................................................................................................... 137 Patient Guideline Sources.......................................................................................................... 137 Finding Associations.................................................................................................................. 139 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 143 Overview.................................................................................................................................... 143 Preparation................................................................................................................................. 143 Finding a Local Medical Library................................................................................................ 143 Medical Libraries in the U.S. and Canada ................................................................................. 143 ONLINE GLOSSARIES................................................................................................................ 149 Online Dictionary Directories ................................................................................................... 149

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GLUCOSE INTOLERANCE DICTIONARY ............................................................................ 151 INDEX .............................................................................................................................................. 209

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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 glucose intolerance 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 glucose intolerance, 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 glucose intolerance, 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 glucose intolerance. 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 glucose intolerance, 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 glucose intolerance. The Editors

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From the NIH, National Cancer Institute (NCI): http://www.cancer.gov/cancerinfo/ten-things-to-know.

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CHAPTER 1. STUDIES ON GLUCOSE INTOLERANCE Overview In this chapter, we will show you how to locate peer-reviewed references and studies on glucose intolerance.

The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and glucose intolerance, 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 “glucose intolerance” (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: •

Glucose Intolerance and Insulin Resistance in Aging is Related to Abdominal Obesity Source: Diabetes Spectrum. 6(4): 262-263. July-August 1993. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: In this article, the author considers recent findings that glucose intolerance and insulin resistance in aging are related to abdominal obesity. She stresses that some conditions often thought of as inevitable results of aging may instead be avoidable effects of fat accumulation. Topics include abdominal fat as a risk factor for developing glucose intolerance, insulin resistance, dyslipidemia, and hypertension; the link

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between abdominal obesity and the development of NIDDM and cardiovascular disease (CVD); sex and age factors; modest changes in body composition and their effects on glucose metabolism; the relationship between deteriorations in glucose tolerance and insulin resistance; and the possibility that monitoring a simple measure, such as waist size, may lead to early recognition of risk for NIDDM and CVD. 10 references. •

Renal Disease, Insulin Resistance, and Glucose Intolerance Source: Diabetes Reviews. 2(1): 19-28. Winter 1994. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Summary: The author of this review article examines evidence of abnormal insulin action in renal diseases, underlying mechanisms, and potential pathogenetic implications. Hypotheses and controversies are analyzed, and potential areas of further research are identified. The author also discusses the clinical impact of these hormonal disturbances. Specific topics include the factors implicated in the pathogenesis of chronic renal failure (CRF), such as uremic toxins, exercise tolerance, metabolic acidosis, vitamin D deficiency, and anemia; the cellular basic of insulin resistance; glucose intolerance and insulin secretion in CRF; and the clinical implications of insulin abnormalities in CRF, including cardiovascular, metabolic, nutritional, and growth complications. 8 figures. 3 table. 58 references. (AA-M).

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Age and Glucose Intolerance: Effect of Fitness and Fatness. (editorial) Source: Diabetes Care. 26(2): 539-540. February 2003. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: The fact that glucose intolerance increases with age has been apparent for over 30 years, leading to the suggestion at one time that the diagnostic criteria for diabetes be amended to account for this inevitable consequence of the aging process. However, these earlier findings did not differentiate the effects on the plasma glucose response to an oral glucose challenge of age per se from those due to the impact of a number of age-related variables. This editorial serves as an introduction to an article that provides additional information concerning the effect of body fat on glucose tolerance, as apparently healthy volunteers grow older. However, the editorial author notes that the potential effect of differences in fitness, an age-related variable of comparable magnitude, was apparently not considered in their study. The author concludes that loss of glucose tolerance with age is primarily related to weight gain and sedentary lifestyle, and level of physical activity is as powerful a factor as adiposity (body fat deposits) in this regard. The best way to stem the rapidly growing epidemic of type 2 diabetes is by concerted efforts beginning at a young age to prevent fatness and encourage fitness. 17 references.

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Insulin and Hypertension: Relationship to Obesity and Glucose Intolerance in Pima Indians Source: Diabetes. Volume 39: 1430-1435. November 1990. Summary: The relationships among blood pressure, obesity, glucose tolerance, and serum insulin concentration were studied in 2,873 Pima Indians aged 18 to 92 years. Age-and sex-adjusted to the Pima population, the prevalence of hypertension was 7.1 percent for subjects with normal glucose tolerance, compared with 13.0 percent for

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subjects with impaired glucose tolerance, and 19.8 percent for those with noninsulindependent diabetes mellitus (NIDDM). The authors conclude that insulin is not significantly related to blood pressure in Pima Indians not receiving antihypertensive drugs. Higher insulin concentrations in drug-treated hypertensive patients might result from the treatment rather than contribute to the pathogenesis of hypertension. Thus, these data do not support a major role for insulin in determining the occurrence of hypertension or regulation of blood pressure in Pima Indians. 5 figures. 4 tables. 59 references. (AA-M). •

Low Birth Weight, Family History of Diabetes, and Glucose Intolerance in Swedish Middle-Aged Men Source: Diabetes Care. 22(7): 1043-1047. July 1999. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Summary: This article describes a population based, cross sectional study that investigated the influence of family history of diabetes on the association between low birth weight and glucose intolerance. The study population consisted of 2,237 men born from 1938 to 1957 in four municipalities at the outskirts of Stockholm, Sweden. Fifty of the men had a family history of diabetes. Oral glucose tolerance testing detected 35 cases of type 2 diabetes, 102 cases of impaired glucose tolerance, and 57 cases of impaired fasting glucose. The study found that men whose birth weight was less than or equal to 3,000 grams were more than four times as likely to have diabetes as men whose birth weight was greater than or equal to 3,601 grams. For impaired glucose tolerance and impaired fasting glucose, the corresponding estimates were 1.9 and 2.6, respectively. In subjects with a family history of diabetes, the corresponding figures were approximately similar, except for diabetes, for which the odds ratio was 5.4. For men who had low birth weight in combination with a family history of diabetes, the odds ratio was 10.9 for diabetes, 2.4 for impaired glucose tolerance, and 5.9 for impaired fasting glucose. The article concludes that low birth weight is an important determinant of glucose intolerance but that the combination of low birth weight and family history of diabetes is particularly important to the risk of developing diabetes. 4 tables. 28 references. (AAM).

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Gestational Diabetes: Antepartum Characteristics That Predict Postpartum Glucose Intolerance and Type 2 Diabetes in Latino Women Source: Diabetes. 47(8): 1302-1310. August 1998. Summary: This article describes a study that examined antepartum clinical characteristics along with measures of glucose tolerance, insulin sensitivity, pancreatic beta cell function, and body composition in Latino women with gestational diabetes mellitus (GDM) for their ability to predict type 2 diabetes or impaired glucose tolerance (IGT) within 6 months after delivery. A total of 122 islet cell antibody-negative women underwent an oral glucose tolerance test (OGTT) and an intravenous glucose tolerance test (IVGTT), hyperinsulinemic-euglycemic clamps, and measurement of body fat between 29 and 36 weeks of gestation and returned between 1 and 6 months postpartum for a 75-gram OGTT. Logistic regression analysis was used to examine the relationship between antepartum variables and glucose tolerance status postpartum. Results revealed that, at postpartum testing, 40 percent of the cohort had normal glucose tolerance, 50 percent had IGT, and 10 percent had diabetes by American Diabetes Association criteria. Independent antepartum predictors of postpartum diabetes were

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the 30-minute incremental insulin:glucose ratio during a 75-gram OGTT and the total area under the diagnostic 100-gram glucose tolerance curve. Independent predictors of postpartum IGT were a low first-phase IVGTT insulin response, a diagnosis of GDM before 22 weeks of gestation, and weight gain between prepregnancy and the postpartum examination. All subjects had low insulin sensitivity during late pregnancy, but neither glucose clamp nor minimal model measures of insulin sensitivity in the third trimester were associated with the risk of IGT or diabetes within 6 months after delivery. Results highlight the importance of pancreatic beta cell dysfunction, detectable under conditions of marked insulin resistance in late pregnancy, to predict abnormalities of glucose tolerance soon after delivery in pregnancies complicated by GDM. Moreover, the association of postpartum IGT with weight gain and an early gestational age at diagnosis of GDM suggests a role for chronic insulin resistance in mediating hyperglycemia outside the third trimester in women with such a beta cell defect. 1 appendix. 5 figures. 3 tables. 36 references. (AA-M). •

Epidemiology of Glucose Intolerance and Gestational Diabetes in Women of Childbearing Age Source: Diabetes Care. 21(Supplement 2): B9-B13. August 1998. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: This article examines epidemiological data on gestational diabetes mellitus (GDM) from several sources. Available data suggest that the frequency of diabetes in pregnancy is highly variable, generally reflecting the underlying pattern of type 2 diabetes in the particular population. Different ethnic groups in the same environmental setting experience widely variable risk. Impaired glucose tolerance is usually more prevalent than diabetes in women of childbearing age. Maternal age, overweight, parity, and family history of diabetes all predispose to GDM. Incidence is low in the absence of risk factors, suggesting that selective screening programs may be cost-effective. Adverse outcome may be more frequent in women with impaired glucose tolerance than in women with normal tolerance. Programs to reduce the incidence of subsequent type 2 diabetes in women who have GDM may be cost effective to health services and improve the quality of life for those concerned. The worldwide epidemic of glucose intolerance predicted by the latest World Health Organization studies will undoubtedly increase the burden of GDM, especially in developing countries. 3 figures. 6 tables. 24 references. (AA-M).

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Inverse Association Between Fish Intake and Risk of Glucose Intolerance in Normoglycemic Elderly Men and Women Source: Diabetes Care. 14(11): 935-941. November 1991. Summary: This article reports on a research study undertaken to examine the association of fish intake with the subsequent risk of impaired glucose tolerance and diabetes mellitus (glucose intolerance). In 1971, information about food intake was obtained by the cross-check dietary history method on 175 men and women aged 64 to 87 years who were normoglycemic and free of clinical diabetes. During the follow-up period from 1972 to 1975, an oral glucose tolerance test was performed annually, and in 59 of 175 elderly people a diagnosis of glucose intolerance was made at least once. The results showed that in fish eaters, the incidence of glucose intolerance was significantly lower compared with nonfish eaters. The authors conclude that, in an elderly population, the habitual consumption of a small amount of fish may protect against the

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development of impaired glucose tolerance and diabetes mellitus. 6 tables. 49 references. (AA-M). •

Hypercholesterolemia in Diabetes and Glucose Intolerance in the U.S. Population Source: Diabetes Care. 14(5): 366-374. May 1991. Summary: This article reports on the prevalence of hypercholesterolemia, according to the guidelines of the National Cholesterol Education Program, which has been determined in a national survey of diabetes and glucose intolerance. Rates of elevated total cholesterol in people with diabetes in the United States are only slightly greater than in those without diabetes after adjusting for age and sex. Nevertheless, high or borderline high total cholesterol is common in diabetes and is present in 70 percent of adults with diagnosed diabetes and 77 percent with undiagnosed diabetes. The authors discuss the findings as they apply to risks for coronary heart disease. The authors conclude that investigation of blood lipid levels and coronary heart disease risk factors should be routine in all patients with diabetes, and treatment strategies should include management of lipid disorders and the multiple other risk factors for coronary heart disease that are highly prevalent in these patients. 2 figures. 7 tables. 50 references. (AAM).

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Long-Term (5-Year) Effects of a Reduced-Fat Diet Intervention in Individuals with Glucose Intolerance Source: Diabetes Care. 24(4): 619-624. April 2001. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: This review article reports on a study that determined whether reducing dietary fat would reduce body weight and improve long term glycemia in people with glucose intolerance. The study design was a 5 year follow up of a 1 year randomized controlled trial of a reduced fat ad libitum diet versus a usual diet. Participants with glucose intolerance were recruited from a Workforce Diabetes Survey conducted in 41 work sites around Auckland, New Zealand, between 1988 and 1990. The group that was randomized to a reduced fat diet participated in monthly small group education sessions on reduced fat eating for 1 year. Body weight and glucose tolerance were measured in 136 participants at baseline, 6 months, and 1 year, with follow up at 2 years, 3 years, and 5 years. Of the 136 participants who completed the 1 year intervention, 103 were reassessed at 5 years. The study found that, compared with the control group, weight decreased in the reduced fat diet group. The greatest difference was noted at 1 year, diminished at subsequent follow up, and was no longer present by 5 years. Glucose tolerance also improved in patients on the reduced fat diet. A lower proportion had type 2 diabetes or impaired glucose tolerance at 1 year, but in subsequent years, there were no differences between groups. However, the more compliant 50 percent of the intervention group maintained lower fasting 2 hour glucose at 5 years compared with control subjects. The article concludes that the natural history for people at high risk of developing type 2 diabetes is weight gain and deterioration in glucose tolerance. This process may be ameliorated through adherence to a reduced fat intake. 2 figures. 3 tables. 26 references. (AA-M).

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Federally Funded Research on Glucose Intolerance The U.S. Government supports a variety of research studies relating to glucose intolerance. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.2 CRISP (Computerized Retrieval of Information on Scientific Projects) is a searchable database of federally funded biomedical research projects conducted at universities, hospitals, and other institutions. Search the CRISP Web site at http://crisp.cit.nih.gov/crisp/crisp_query.generate_screen. You will have the option to perform targeted searches by various criteria, including geography, date, and topics related to glucose intolerance. 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 glucose intolerance. The following is typical of the type of information found when searching the CRISP database for glucose intolerance: •

Project Title: CAH: CALCIUM CHANNELS AS THERAPEUTIC TARGETS Principal Investigator & Institution: Loechner, Karen J.; Professor; Pediatrics; University of North Carolina Chapel Hill Aob 104 Airport Drive Cb#1350 Chapel Hill, Nc 27599 Timing: Fiscal Year 2004; Project Start 01-FEB-2004; Project End 31-JAN-2009 Summary: (provided by applicant): This K08 application under the co-mentorship of Drs. Bob Rosenberg and Gerry Oxford has two goals: 1) to understand the cellular mechanisms that underlie coupling of voltage-activated calcium channels to regulated peptide secretion in the anterior pituitary, and 2) to assess the clinical impact of targeted calcium channel blockade in Congenital Adrenal Hyperplasia (CAH), a disorder resulting from pituitary hypersecretion. In studies of a pituitary corticotroph cell line (AtT-20) I identified three distinct high voltage-activated calcium channels that are expressed in similar abundance. Despite this, only the L-type [dihydropyridine (DHP)sensitive] channel is capable of triggering calcium-dependent secretion of ACTH. The primary focus of this proposal, therefore, is to examine the mechanisms that underlie the coupling of DHP-sensitive channels to ACTH release. I hypothesize that differential localization of the L-type channels accounts for the distinct function of the neurosecretory apparatus in ACTH-secreting cells. I propose to: a) examine the cellular sites of calcium channels and synaptic components using immunocytochemistry/ confocal microscopy, and b) disrupt coupling using a dominant-negative approach. In CAH, the most common adrenal disorder in children, a molecular defect in cortisol production removes normal negative feedback to the anterior pituitary and results in elevated ACTH secretion. Elevated ACTH further increases cortisol precursors, and shunts these steroid intermediates to androgen synthetic pathways. The clinical stigmata (e.g., ambiguous genitalia, virilization and short stature in adults) are due to the excess in androgens. Treatment requires life-long glucocorticoid replacement to restore the normal feedback mechanism. Determining the "optimal level" ofglucocorticoid replacement, however, is difficult: under-treatment leads to adrenal insufficiency and androgen excess; over-treatment leads to glucocorticoid excess (e.g., obesity, glucose intolerance and osteopenia). My work with the pituitary cells in culture suggests that

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Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).

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selective pharmacologic blockade of L-type (DHP-sensitive) channels, and, in turn, attenuation of ACTH release, will provide a novel adjunct therapy by allowing lower glucocorticoid dosing. This would result in enhanced linear growth and improved bone mineral density. These basic research and clinical studies complement one another, and together, they should enhance our understanding of the cellular mechanisms underlying peptide secretion. Furthermore, they may allow for improved treatment in hypersecretory conditions, such as CAH. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CARDIOVASCULAR HEALTH IN CHILDREN AND YOUTH (CHIC III) Principal Investigator & Institution: Harrell, Joanne S.; Professor; None; University of North Carolina Chapel Hill Aob 104 Airport Drive Cb#1350 Chapel Hill, Nc 27599 Timing: Fiscal Year 2002; Project Start 01-MAR-1990; Project End 30-JUN-2004 Summary: This continuation of the Cardiovascular Health in Children and Youth Study (CHIC III) will investigate the childhood development of several risk factors for cardiovascular disease (CVD) and the aggregation of those risk factors over time. One recognized aggregation, or cluster, of risk factors is commonly linked to Type 2 diabetes and CVD in adults. This aggregation is called the insulin resistance syndrome and consists of related metabolic abnormalities including dyslipidemia (high triglyceride and low high density lipoprotein cholesterol [HDL-C], hypertension, hyperinsulinemia, and glucose intolerance). Obesity is thought by some to also be a part of the syndrome. At this time, little is known about the prevalence or development of the insulin resistance syndrome during childhood and adolescence. In addition, no studies have examined insulin resistance in youth with regard to eating habits, physical activity and maturational level, all of which can affect various risk factors, particularly those in the insulin resistance syndrome. Using an accelerated, longitudinal (cohort-sequential) design, CHIC II subjects and additional adolescent and preadolescent children will be followed through all stages of puberty. CVD risk factors as well as aggregation of specific factors into the insulin resistance syndrome will be studied. The contribution of obesity, heredity and environmental factors (broadly defined), as well as a newer risk factor (lipid particle subclass profiles), will also be examined to determine their effects on the emergence, aggregation and developmental course of risk factors for CVD. Youth in three cohorts, aged 8-18, will be evaluated annually for risk factors of CVD for 4 years or until they graduate from high school. We will measure: blood pressure; body mass index; skinfolds; waist and other circumferences; insulin, glucose, and lipids via venipuncture; CV fitness; eating habits; physical activity; and smoking to examine the emergence, aggregation and developmental course of risk factors across all stages of puberty. We will also store all blood for possible future genetic studies as well as gather data from parents on the family history of CVD and their personal health habits. This is a cost effective way to obtain these data, as we will be able to capitalize on the data already collected for CHIC II subjects. Major analysis will include general linear models and latent class models. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CARDIOVASCULAR RISK IN SECOND GENERATION SOUTH ASIAN AME Principal Investigator & Institution: Agarwal, Simi; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106

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Timing: Fiscal Year 2002 Summary: Several studies from the United States, South Africa and the United Kingdom have documented an increased risk of cardiovascular disease in immigrants from the Indian subcontinent when compared to people of European orgin. Several risk factors have been identified as increased in South Asian immigrants including lipoprotein (a), insulin resistance and glucose intolerance, truncal obesity, and total cholesterol:HDL ratio. Furthermore, both anecdotal and scientific evidence shows an increased morbidity from cardiovascular events in South Asian males. There have not been, however, any studies to date assessing the risk factors of cardiovascular morbidity in second generation South Asians born in the United States. The objective of this study is to determine whether second generation American-born South Asians have poorer prognostic cardiovascular risk profiles compared to white Americans. The reason this question is important is that it is unclear what the relationship is between the risk for heart disease someone inherits from his/her parents and the risk for heart disease which may come about by living in a particular environment. In order to understand this relationship, we will recruit a group of American born South Asians aged 18-30 who are children of immigrants, and a group of American born whites aged 18-30. Through these 18-30 year olds, we will be able to enlist the participation of their parents aged 4570. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CHARACTERIZING AND MAPPING OBESITY AND DIABETES GENES Principal Investigator & Institution: Naggert, Juergen K.; Staff Scientist; Jackson Laboratory 600 Main St Bar Harbor, Me 04609 Timing: Fiscal Year 2001; Project Start 15-SEP-1998; Project End 31-AUG-2004 Summary: Non insulin dependent diabetes mellitus (NIDDM) is a major health problem which affects an estimated 5-10 percent of the American population. Although NIDDM is highly heritable in humans, its inheritance does not follow simple Mendelian laws and is, therefore, thought to be caused by the simultaneous action of many genes. Because such polygenic inheritance is still very difficult to unravel, single gene mutant models offer significant advantages for gene identification and for detailed physiological studies. Five recently cloned single gene obesity mutations in mouse have provided exciting new insights into the etiology of obesity. In contrast, identification of NIDDM genes is delayed, because single gene mouse mutations for NIDDM are lacking. We have identified a new mouse model for maturity onset NIDDM, which apparently is due to a recessive single gene mutation, that has provisionally been named sugar baby (sub). The Tallyho-sub/sub mouse stock is characterized by glucose intolerance, hyperinsulinemia, chronic hyperglycemia, and increased body weight. We have carried out a preliminary outcross to a nondiabetic, nonobese mouse strain to map the sub diabetes mutation. In this cross, in addition to the sub locus which determines plasma glucose levels, we were able to map a second locus, nicknamed 'brother of sub' (bos), which controls body weight. We also found evidence that the two loci interact epistatically, i.e. homozygosity at the bos locus is necessary for sub/sub mice to become diabetic. In contrast, homozygous bos/bos mice without the sub gene do not become diabetic. Based on our preliminary results, we hypothesize that the Tallyho strain carries a major obesity susceptibility allele (bos) that interacts with the sub mutation to produce the obese/diabetic phenotype of Tallyho-sub/sub mice. To test this hypothesis, we propose to carry out two specific aims. a.) to construct separate congenic lines of mice that carry either the bos and sub genes individually or in combination on a common

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genetic background and to use these lines to generate fine structure genetic maps for bos and sub in order to positionally clone these genes. b.) to physiologically characterize the Tallyho strain and the congenic lines and test the hypothesis that the sub gene can interact with obesity mutations other than bos to cause diabetes. At the successful conclusion of this work, we will have identified two new genes, bos and sub, that constitute an epistatic genetic system involved in the etiology of type II diabetes. Additionally, through examination of the mutations individually and in combination in a common genetic background, we will gain a better understanding of the pathways and physiological abnormalities that are necessary to cause diabetes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CHICAGO CHILDHOOD DIABETES REGISTRY Principal Investigator & Institution: Lipton, Rebecca B.; Associate Professor; Pediatrics; University of Chicago 5801 S Ellis Ave Chicago, Il 60637 Timing: Fiscal Year 2003; Project Start 30-SEP-1992; Project End 31-MAY-2008 Summary: (provided by applicant): Recent increases in childhood diabetes present an urgent public health challenge: to mount effective primary and secondary prevention efforts as soon as possible. We must therefore understand the mechanisms underlying the current epidemic, particularly the interaction of genetics with the changing epidemiology of behavioral risk factors. We propose to investigate the determinants of childhood diabetes risk in affected probands and their family members. This is a competing continuation application for the population-based Chicago Childhood Diabetes Registry. This database represents the largest number of non-Hispanic black children with diabetes worldwide, and the largest patient database for Latino children in the continental US. Ongoing ascertainment of incident cases will provide basic epidemiologic data and will anchor a further effort, in families of affected children, to describe the spectrum of youth-onset glucose intolerance in terms of inheritance and the expression of disease susceptibility alleles within families. We will specifically address these hypotheses: 1. That diabetes in youth is caused by a spectrum of etiologic processes, from the insulinopenia of autoimmune type 1 to obesity-related, insulinresistant type 2 diabetes. A subset of children demonstrate a mixed etiology, with autoimmune beta-cell destruction aggravated by the presence of insulin resistance due to genetic susceptibility, obesity and/or physical inactivity. 2. That secular changes in the epidemiology of childhood diabetes are directly related to changes in the prevalence of both type 1 and type 2 risk factors, including obesity, physical inactivity, and perinatal exposures. 3. That familial aggregation of specific traits affects the risk of chronic complications in young people with diabetes, over and above that of glycemic control. Ultimately, this approach will permit a truly population-based molecular epidemiologic study of early-onset diabetes in families from a range of ethnic groups. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CONTROL OF CAMP-MEDIATED GLUCAGON RESPONSE BY BILE ACIDS Principal Investigator & Institution: Bouscarel, Bernard E.; Associate Research Professor; Medicine; George Washington University 2121 I St Nw Washington, Dc 20052 Timing: Fiscal Year 2002; Project Start 01-SEP-2001; Project End 31-JUL-2006 Summary: Cholestatic liver disease with cirrhosis in particular, is the 9th leading cause of death in the USA. Prognosis is poor, with a generally irreversible condition marked by progressive destruction of liver cells. Around 50 percent of patients with liver disease

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and 80 percent of cirrhotic patients display glucose intolerance associated with decreased gluconeogenic response to glucagon. Regulation of helpatocellular metabolism by glucagon is in part through increased cAMP synthesis. The central hypothesis is that certain bile acids alter the glucagon receptor-stimulatory G protein (Gs) coupling through a phosphorylation/dephosphorylation mechanism and that these alterations are responsible for attenuation and delayed recovery of glucagon responsiveness in cholestasis. We have shown that bile acids inhibit hepatic glucagoninduced cAMP synthesis at physiologic concentrations. The effect was at the level of receptor-Gs coupling, most likely through phosphorylation, and was mediated by a calcium-dependent PKC. We have reported that hepatic glucagon-mediated cAMP production was attenuated in cholestasis in hamster induced by ligation of the common bile duct (BDL). Bile acids were either without or with reduced effects after BDL suggesting that the site of cAMP synthesis cascade altered in cholestasis is the same as that altered by bile acids. Specific aims will test the hypotheses: 1)that short-term incubation of hepatocytes with bile acids leads to decreased glucagon receptor-Gs coupling through a phosphorylation/dephosphorylation mechanism involving PKC; 2)that alteration of both glucagon receptor-Gs coupling and receptor dephosphorylation are responsible for the respective attenuation and delayed recovery of glucagon responsiveness in cholestasis. In HEK293 clones expressing glucagon receptor, and in hepatocytes from BDL hamsters we will study the respective effect of physiologic/pathophysiologic bile acid concentrations and cholestasis on receptor/Gs coupling and phosphorylation using a multifaceted approach designed to determine the protein phosphorylation target. We will study the role of protein phosphatases on the time course of glucagon response recovery in cholestasis. Knowledge gained from these studies will have bearing on both diagnosis and treatment of cholestatic hepatobiliary disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CORE--NUTRITION INTERVENTION Principal Investigator & Institution: Campbell, Marci K.; Associate Professor and Director, Cancer; University of North Carolina Chapel Hill Aob 104 Airport Drive Cb#1350 Chapel Hill, Nc 27599 Timing: Fiscal Year 2002 Summary: (adapted from the application): We propose a CNRU that is specifically designed to enhance the translation of basic science information and technology into population-based and clinical nutrition research, and also to facilitate the transfer of ideas and information in the opposite direction. These population-based studies are the major approach for prevention research, which requires the study of many subjects to detect the smaller magnitude changes in outcome measures that typify nutrition versus drug studies. A major reason to locate a CNRU at UNC-CH is the strength and interdisciplinary breadth of our research programs in nutrition. Fifty-five active investigators conduct research that spans areas of basic, clinical and applied science relevant to human nutrition, including clinical nutrition, metabolic biochemistry, molecular biology, gastroenterology, hepatology, pharmacology, health behavior, nutrition epidemiology, physiology, oncology, and endocrinology. Excellent graduate students and postdoctoral fellows are working with CNRU investigators, and CNRU faculty are the awardees for four T32 training grants from the NIDDK, NHLBI, NIEHS and NCI. Our research base generates more than $20 million in annual NIH-funded (or equivalent) nutrition-related research support. CNRU faculty are appointed in many departments including nutrition, medicine, pharmacology, pediatrics, biostatistics,

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epidemiology, cell and molecular physiology, pathology, and environmental. Steven Zeisel, MD serves as CNRU director, and Rosalind Coleman, MD as associate director. An internal governance committee (consisting of the director, associate director, three core directors, and two representatives of the CNRU faculty) will maintain the quality, objectivity and continuity of policies that govern the CNRU. An external advisory committee will be established. The Administrative Core will be responsible for management of the CNRU and will provide biostatistical support, grant pre-review services, facilitation of access to research populations, computer support, an enrichment program, a medical student education program (including leadership of a national curriculum initiative), a pilot and feasibility grant program, a young investigator award, community outreach and public education. Several of these activities will be conducted in collaboration with the UNC-CH General Clinical Research Center. The proposed Translational Core for Population Studies, led by Lenore Kohlmeier, Ph.D., is designed to facilitate the translation of new findings and technology into ongoing research projects and to stimulate the incorporation of state of the art methodology in population based human nutrition studies. The core services will be in five areas: incorporation of biomarkers of dietary intake in ongoing studies, technical support in the preparation of multi-media based dietary assessment, statistical support in the design and analyses of epidemiological studies, support in the preparation of and access to nutritional data on foods and nutrient supplements for estimation of intakes and support with the complex statistical analyses needed to insure the appropriate conclusions from population studies on diet and health. The purpose of the Molecular Biology and Nutritional Biochemistry Core, directed by Melinda Beck, Ph.D., is to provide a state-of-the-art facility for nutrition research investigators. The Core will serve as an educational and training resource for the development and application of molecular biology techniques and biomarkers for nutritional research. It will provide a number of specialized techniques requested by CNRU investigators. In addition, the Core will provide consultation and assistance to investigators who may just be beginning to use molecular techniques and biomarkers in their research. The Nutrition Intervention Core, directed by Marci Campbell, Ph.D., will provide expertise and state-of-the-art resources and techniques for developing and evaluating nutritional interventions aimed at promoting health and preventing disease in populations at risk. CNRU investigators will have access to intervention development and tracking tools, and will receive help and consultation on their application to each project. Five junior investigators propose P/F projects on Selenium and arsenic toxicity, Gene targeted animal models for CVD, Church-based nutrition intervention in African Americans, Epidemiology of glucose intolerance during pregnancy, and Vitamin D therapy for bone disease in cystic fibrosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DIABETES MECHANISMS

IN

HEMOCHROMATOSIS:

PREVALENCE

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Principal Investigator & Institution: Mcclain, Donald A.; Professor and Director; Internal Medicine; University of Utah Salt Lake City, Ut 84102 Timing: Fiscal Year 2002; Project Start 01-MAR-2002; Project End 31-OCT-2006 Summary: Although the hemochromatosis gene (HFE) has been identified there is little information about the diabetes that often accompanies the disease. We hypothesize nondiabetic homozygotes for mutations in HFE will exhibit a defect in insulin secretion as iron overload develops. This notion is supported by preliminary data obtained in HFE mutant mice. The insulin deficiency will progress to type 2 diabetes only if insulin resistance also occurs, either from cirrhosis or inheritance of type 2 diabetes genes.

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Insulin resistance from cirrhosis is hypothesized to result from excess carbohydrate delivery to peripheral tissues, resulting in excess hexosamine generation, an established cause of insulin resistance. Our specific aims are to: 1. Determine the prevalence of impaired glucose intolerance (IGT) and diabetes in clinically unselected individuals with hemochromatosis by oral glucose tolerance criteria. 2. Determine if a defect in insulin secretion exists in nondiabetic homozygotes with or without iron overload. This will be accomplished using the frequently sampled intravenous glucose tolerance test (FSIVGTT) with insulin levels. Reversibility of the defect will be examined after subjects have undergone phlebotomy. The hypothesis will be verified in studies of isolated islets from mice carrying disrupted or mutant HFE genes. 3. Using animal models, determine if diabetes in hemochromatosis results only when insulin resistance is superimposed on an iron- mediated defect in insulin secretion. 4. Determine the sequence and relative contributions of insulin resistance and hepatic glucose production (HGP) in the evolution of diabetes in human hemochromatosis. Insulin resistance and HGP will be quantified by the hyperinsulinemic euglycemic clamp and stable isotope techniques in subjects with hemochromatosis who have normal or IGT, with or without hepatic involvement. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DOES HYPERGLYCEMIA PREDICT PANCREATIC CANCER DIAGNOSIS? Principal Investigator & Institution: Chari, Suresh T.; Mayo Clinic Coll of Medicine, Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2007 Summary: (provided by applicant): Pancreatic cancer causes glucose intolerance and diabetes in up to 80% of patients. Pancreatic cancer induced diabetes (PaCDM) is often asymptomatic, of short duration (50 years of age may have PaCDM. We propose to establish whether newly elevated fasting blood glucose (FBG) is indicative of underlying pancreatic cancer as evidenced by diagnosis of pancreatic cancer within 3 years of the FBG measurement. If so, this would provide an entirely novel approach to screening for sporadic pancreatic cancer. We hypothesize that the 3-year likelihood of diagnosis of pancreatic cancer will be high in subjects: a) equal to or > 50 years of age with newly elevated FBG, b) with elevated fasting glucose who have known risk factors for pancreatic cancer (e.g. smoking), and/or c) who manifest an abrupt increase in FBG in serial measurements over time. We will identify visits to Mayo Clinic between years 1988 to 2002 by subjects equal to or >50 years of age who resided in its surrounding catchment area and had a routine physical examination that included a FBG. Preliminary data reveal that about 150,000 different subjects made >300,000 such visits during this time period providing >1 million person-years of follow-up. We will electronically retrieve clinical, and laboratory data and examine 3-year follow-up from date of FBG measurement to identify those diagnosed with pancreatic cancer. We expect 340 to 510 pancreatic cancer events in this cohort. Our Specific Aims are: Aim 1A). To test if FBG drawn during routine physical examination predicts likelihood of underlying pancreatic cancer and to test for non-linearity of this association. Aim 1B) To establish a FBG threshold that predicts a high 3-year likelihood of diagnosis of pancreatic cancer. Aim 2). To estimate the extent to which known risk factors for pancreatic cancer (age, smoking, obesity and family history) modify the likelihood of underlying pancreatic cancer in subjects with FBG greater than the threshold defined by Aim 1B. Aim 3). To test if patterns of change in serial measurements of FBG over time predict likelihood of underlying pancreatic cancer. The clinical and research implications of this study are

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considerable. These data may lead to delineation of individuals who have a high likelihood of existing pancreatic cancer, and who may be ideal candidates for more intensive screening or early detection regimens. The research described in this application is 100% relevant to pancreatic cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EFFECTS OF SLEEP APNEA ON METABOLIC FUNCTION Principal Investigator & Institution: Punjabi, Naresh M.; Assistant Professor; Medicine; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-JUL-2007 Summary: (provided by applicant): Sleep apnea is a chronic condition associated with an increased risk of hypertension and cardiovascular disease. Recent data suggest that sleep apnea is also associated with metabolic dysfunction that is characterized by glucose intolerance and insulin resistance. Although several studies indicate that the association between sleep apnea and metabolic dysfunction is independent of confounders including obesity, it remains to be determined whether the association is causal. Moreover, whether intermittent hypoxemia and/or sleep fragmentation are in the putative causal pathway is unknown. The major objective of our proposal is to determine whether sleep apnea produces metabolic dysfunction and delineate the underlying mechanisms. Our primary hypothesis is that intermittent hypoxemia and recurrent arousals from sleep lead to acute and chronic changes in metabolic function. In Specific Aim 1, we will examine whether nighttime and daytime profiles of metabolic function differ between patients with sleep apnea and control subjects matched on age, race, gender, and obesity. We hypothesize that, compared to control subjects, patients with sleep apnea will demonstrate: a) marked abnormalities in nighttime profiles of glucose, insulin, and insulin secretion rate; b) impairment in daytime glucose tolerance, insulin sensitivity, and glucose effectiveness; and c) an increase in sympathetic activity and serum levels of leptin, cortisol, IL-6, and TNF-ct that are independently correlated with the severity of intermittent hypoxemia and frequency of arousals. In Specific Aim 2, we will examine whether experimental sleep fragmentation and sleep apnea (sleep fragmentation with intermittent hypoxemia) alter metabolic dysfunction in normal subjects. We hypothesize that: a) sleep fragmentation in normal individuals will alter nighttime profiles of glucose, insulin, and insulin secretion rate and worsen daytime measures of glucose tolerance, insulin resistance, and glucose effectiveness; b) intermittent hypoxemia in association with sleep fragmentation will potentiate the adverse effects of sleep fragmentation alone; and c) experimental sleep fragmentation and sleep apnea will increase sympathetic activity and serum levels of cortisol, leptin, TNF-alpha and IL-6 in association with impaired glucose homeostasis. Novel experimental paradigms have been developed to determine the independent roles of sleep fragmentation and sleep apnea on metabolic function. Given the epidemic of obesity and diabetes, understanding the role of sleep apnea as a risk factor for metabolic dysfunction has public health significance in terms of prevention and treatment of diabetes, hypertension, and cardiovascular disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: FASTING, INSULIN ACTION & POST-PRANDIAL METABOLISM Principal Investigator & Institution: Bergman, Bryan C.; Pediatrics; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2002; Project Start 01-JUL-2002

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Summary: (Scanned from the applicant's description) Obesity is a public health epidemic that is commonly associated with insulin resistance, and predisposes people to development of Type II diabetes. I am interested in how insulin resistance affects nutrient metabolism, particularly in the post-prandial state, and the implications of this for obesity and diabetes. In the future, I intend to investigate effects of fasting and caloric restriction on post-prandial metabolism in lean, obese, and post-obese subjects. Acute changes in insulin action, despite having different origins to chronic insulin resistance, can profoundly affect nutrient metabolism. For example, two days of fasting induces glucose intolerance following a normal mixed meal, and promotes non-hepatic decreased insulin action. The proposed study will investigate the effects of an acute change in insulin action induced by fasting, on post-prandial nutrient partitioning in lean and obese men and women. The relative oxidation rates of meal- derived lipid and carbohydrate will be determined in addition to storage of meal derived nutrients. It is hypothesized that glucose intolerance induced by fasting will be associated with a) greater post-prandial lipid oxidation (endogenous and meal-derived), and b) greater storage of meal derived carbohydrate as glycogen. As these data have direct implications for weight reduction practices, studies will be performed in both lean and obese, men and women. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENE, INTRAUTERINE ENVIRONMENT AND PCOS Principal Investigator & Institution: Dunaif, Andrea E.; Chief, Division of Women's Health; Northwestern University 633 Clark Street Evanston, Il 602081110 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2007 Summary: Polycystic ovary syndrome (PCOS) is among the most common endocrine disorders in premenopausal women. Women with PCOS have profound insulin resistance as well as pancreatic beta-cell dysfunction, independent of obesity and glucose intolerance. However, skeletal muscle insulin resistance reverse in cultured myotubes suggesting that insulin resistance in this tissue is induced by factors in the in vivo environment. We have recently shown that hyperandrogenemia is the reproductive phenotype in males as well as female relatives of PCOS women. Moreover, Urbanek and colleagues have shown (Project 2) that this phenotype appears to have a genetic basis in PCOS families and shows significant linkage and association with a marker locus on chromosome 19P in the region of the insulin receptor (allele 8 of D19S884). We now have extremely existing evidence that this allele is also associated with a metabolic phenotype in PCOS probands and their brothers: increased post-challenge glucose levels, apparent defects in insulin secretion, especially in response to sulfonylurea, and accelerated weight gain with age. Abbott (Project 3) has shown that in utero testosterone excess can reproduce many features of the PCOS reproductive and metabolic phenotype in female rhesus monkeys, including decreased insulin secretion and increased LH levels. Levine (Project 4) has shown that one mechanism for these changes is androgen-mediated sulfonylurea-stimulated insulin secretion by the pancreatic beta cells. Taken together, these observations have led to a new hypothesis for the etiology of PCOS: genetic variation resulting in hyperandrogenemia results in many of the reproductive and metabolic features of PCOS by fetal androgen programming. In this Project, we will test two components of the hypothesis. First, is the metabolic phenotype that is associated with the marker locus decreased insulin secretion, consistent with androgen-mediated suppression of K+/ATP channels? Second, is there in utero androgen excess, decreased fetal insulin secretion and/or intrauterine growth retardation (IUGR) in the female

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offspring of PCOS women, and does the marker allele identify a subpopulation of offspring with these findings? Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GLUCOSE TOLERANCE IN HIV INFECTED PATIENTS ON PROTEASE INHIBITOR THER Principal Investigator & Institution: Erbelding, Emily J.; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002 Summary: The pathogenesis of glucose intolerance in patients taking PI therapy and developing diabetes is not known. The oral glucose tolerance test has been used clinically to screen for diabetes mellitus. We propose to use the oral glucose tolerance test to address the specific aims outlined below: 1. To determine if use of protease inhibitors is associated with glucose intolerance. 2. To determine if acute phase insulin release is appropriate in patients on protease inhibitors. The patient population for this study will be adult men and women with HIV infection, with no prior history of diabetes who are about to initiate antiretroviral therapy using one or more protease inhibitors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GLUCOSE TRANSPORTER REGULATION IN OBESITY AND DIABETES Principal Investigator & Institution: Kahn, Barbara B.; Chief; Beth Israel Deaconess Medical Center St 1005 Boston, Ma 02215 Timing: Fiscal Year 2002; Project Start 01-FEB-1992; Project End 31-JAN-2006 Summary: Recent studies challenge long-held paradigms about the role of specific insulin target tissues in whole body insulin action and in the pathogenesis of insulin resistance. Studies in this application will investigate the importance of the Glut4 glucose transporter in muscle and adipose tissue, and the dynamic interactions by which altering glucose transport in one of these tissues may cause insulin resistance in other insulin target tissues including liver. The overall goal is to determine the role of glucose transport in adipose tissue and in muscle in whole body glucose homeostasis. Our preliminary data indicate that markedly reducing Glut4 expression selectively in adipose tissue causes insulin resistance and glucose intolerance which are as severe as knocking out Glut4 from muscle. This is important since in humans with obesity and type 2 diabetes, Glut4 expression is down-regulated in adipocytes but not in skeletal muscle. We also find that mice with muscle specific Glut4 knockout eventually become insulin resistant in fat and liver. We will investigate the molecular mechanisms for these effects. Specific aims are: 1) To determine the mechanisms by which altering Glut4 expression selectively in adipocytes affects whole body glucose homeostasis. 2) To determine what genes/molecules mediate the effects of altered Glut4 expression in adipocytes on whole body glucose homeostasis. 3) To determine the role of brown adipose tissue in the insulin resistance caused by reduced Glut4 expression is adipose tissue. 4) To determine the mechanisms by which altering Glut4 expression selectively in muscle affects insulin action in other tissues. 5) To determine whether combined knockout of Glut4 from adipose tissue and muscle will lead to greater insulin resistance than knockout from either tissue alone and how this is affected by genetic background. These studies will lead to a better understanding of the mechanisms for regulation of glucose homeostasis and the role of impaired glucose transport, which is present in

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adipocytes and muscle of humans with obesity and type 2 diabetes, in the pathogenesis of insulin resistance. Our goal is to find new therapeutic targets to prevent or ameliorate type 2 diabetes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HAPO: DATA COORDINATING CENTER Principal Investigator & Institution: Dyer, Alan R.; Professor and Associate Chair; Preventive Medicine; Northwestern University Office of Sponsored Research Chicago, Il 60611 Timing: Fiscal Year 2002; Project Start 04-MAY-1999; Project End 31-MAR-2004 Summary: There is a consensus that overt diabetes mellitus (DM), whether or not accompanied by symptoms or signs of metabolic decompensation, is associated with a significant risk of adverse pregnancy outcome. On the other hand, the risk of adverse outcome associated with degrees of glucose intolerance less severe than overt DM is controversial. The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study is a basic epidemiologic investigation aiming to clarify unanswered questions on the association of various levels of glucose intolerance during the third trimester of pregnancy and risk of adverse outcomes. Its General Aim -- by means of an international cooperative study involving 16 centers and approximately 25,000 pregnant women -- is to achieve a major advance in knowledge on levels of glucose during pregnancy that place the mother, fetus, and neonate at increased risk. The primary hypothesis is that hyperglycemia during pregnancy, less severe than overt DM, is associated with increased risk of adverse maternal, fetal, and neonatal outcome that is independently related to the degree of metabolic disturbance. Specific Aims of HAPO are: 1. to examine glucose tolerance in a large, heterogeneous, multinational, multicultural, ethnically diverse cohort of women in the third trimester of gestation with medical caregivers "blinded" to status of glucose tolerance (except in those instances where fasting and/or two hour OGTT plasma glucose concentration exceeds a predefined cutoff value); and 2. to derive internationally acceptable criteria for the diagnosis and classification of gestational diabetes mellitus (GDM) based on the specific relationships between maternal glycemia and the risk of specific adverse outcomes that are established through this study. The study is to be accomplished with high quality standardized data collection on the women during the third trimester of gestation (including the OGTT) and at time of delivery for assessment of adverse outcomes, including operative delivery (caesarean section), increased fetal size (macrosomia/obesity), neonatal morbidity (hypoglycemia), and fetal hyperinsulinism. HAPO is to include a Clinical Coordinating Center and Data Coordinating Center, both located at the Northwestern University Medical School in Chicago, as well as a Central Laboratory located in Belfast, United Kingdom. This application requests support for the Data Coordinating Center for HAPO. Cost effectiveness for HAPO is enhanced through cost sharing by colleagues in non-U.S. centers. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: HIV PROTEASE INHIBITORS AND GLUCOSE TRANSPORT Principal Investigator & Institution: Mueckler, Michael M.; Professor; Cell Biology and Physiology; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2002; Project Start 15-JAN-2002; Project End 31-DEC-2004 Summary: (Provided by the applicant): The advent of HIV protease inhibitor (PI) therapy was a major advance in the treatment of HIV infection. Combined treatment of

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HIV-infected patients with reverse transcriptase inhibitors and PIs (intensive antiretroviral therapy, IART) has been shown to delay the onset of overt disease and to prolong survival. Current guidelines recommend the use of IART for the treatment of all newly diagnosed cases of HIV infection. Unfortunately, IART is associated with the development of numerous metabolic abnormalities, including peripheral lypodystrophy, hyperlipemia, insulin resistance, glucose intolerance, and type 2 diabetes. The reported incidence of type 2 diabetes in PI-treated patients is at least 10fold greater than that in the general age- and sex-matched population and is particularly alarming considering the relatively young age of the patient populations and the rapidity of diabetes onset after the start of therapy. PIs have recently been shown to rapidly and selectively suppress the activity of Glut4, the insulin-responsive glucose transporter, an effect that can directly account for the insulin resistance and increased incidence of diabetes associated with PI therapy. The long-term goal of this proposal is to elucidate the relationship between the effect of PIs on Glut4 and the metabolic abnormalities associated with IART and to determine the mechanism of the effect of PIs on Glut4 activity. To accomplish these goals, the following specific aims will be pursued: 1) To determine the acute effect of PIs on whole body glucose disposal and glucose transport in skeletal muscle. This aim will directly test the hypothesis that Pls acutely induce whole-body insulin resistance via the inhibition of skeletal muscle Glut4. 2) To determine whether PIs suppress insulin-stimulated glucose transport by direct binding to Glut4. This aim will ascertain whether the PI effect is due to competitive or noncompetitive binding to Glut4 or binding to a molecule involved in the regulation of Glut4 activity in the plasma membrane. 3) To determine whether PIs suppress the activity of Glut isoforms other than Glut4. This aim will address a potentially important clinical issue: whether PIs, as a result of the inhibition of one or more of the other 8 known Glut isoforms, may have iatrogenic effects that have not yet been detected. 4) To determine the structural determinants of Glut4 interaction with PIs. This aim will identify specific Glut4 domains and amino acid residues involved in its predicted binding to PIs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HYPERGLYCEMIA AND ADVERSE PREGNANCY OUTCOME Principal Investigator & Institution: Metzger, Boyd E.; Professor; Medicine; Northwestern University 633 Clark Street Evanston, Il 602081110 Timing: Fiscal Year 2002; Project Start 04-MAY-1999; Project End 31-MAR-2004 Summary: There is a consensus that overt diabetes mellitus (DM), whether or not accompanied by symptoms or signs of metabolic decompensation, is associated with a significant risk of adverse pregnancy outcome. On the other hand, the risk of adverse outcome associated with degrees of glucose intolerance less severe than overt DM is controversial. The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study is a basic epidemiologic investigation aiming to clarify unanswered questions on the association of various levels of glucose intolerance during the third trimester of pregnancy and risk of adverse outcomes. Its General Aim, by means of an international cooperative study involving 16 field centers and approximately 25,000 pregnant women, is to achieve a major advance in knowledge on levels of glucose during pregnancy that place the mother, fetus, and neonate at increased risk. The primary hypothesis is that hyperglycemia, less severe than overt DM, is associated with increased risk of adverse maternal, fetal, and neonatal outcome that is independently related to the degree of metabolic disturbance. Specific Aims of HAPO are: 1. To examine glucose tolerance in a large, heterogeneous, multinational, multicultural, ethnically diverse cohort of women

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Glucose Intolerance

in the third trimester of gestation with medical caregivers "blinded" to status of glucose tolerance (except in those instances where fasting and/or two hour OGTT plasma glucose concentration exceeds a predefined cutoff value); and 2. To provide data that can be used to derive internationally acceptable criteria for the diagnosis and classification of gestational diabetes mellitus (GDM) based on the identification of pregnancies at risk for specific adverse outcomes. The study is to be accomplished with high quality standardized data collection on the women during the third trimester of gestation (including the OGTT) and at time of delivery for assessment of adverse outcomes, including fetal hyperinsulinism, fetal obesity (macrosomia), operative delivery (caesarian section), and neonatal morbidity (hypoglycemia). HAPO is to include field centers and regional centers where the participants will be studied, a Clinical Coordinating Center and Data Coordinating Center, both located at the Northwestern University Medical School in Chicago, as well as a Central Laboratory located in Belfast, Northern Ireland. This application requests support for the Clinical Coordinating Center, the field and regional centers and Central Laboratory. Cost effectiveness for the HAPO study is enhanced through cost sharing by colleagues in non-U.S. centers. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INSULIN & GLUCOSE SIGNALING PATHWAYS IN ISLET BETA CELLS Principal Investigator & Institution: Kulkarni, Rohit N.; Assistant Professor; Joslin Diabetes Center Boston, Ma 02215 Timing: Fiscal Year 2002; Project Start 15-SEP-2000; Project End 31-AUG-2005 Summary: (adapted from the application) Type 2 diabetes is characterized by insulin resistance and beta-cell failure resulting in uncontrolled hyperglycemia. The basis of the beta-cell defect is presently unclear. A growing body of evidence indicates insulinsignaling proteins are present in the islets and contribute to the maintenance of glucose homeostasis. Thus, normal beta-cells show glucose-stimulated phosphorylation of the insulin receptor (IR) and insulin receptor substrate-1 (IRS-1). Secondly, mice with a targeted disruption of the IR show loss of insulin secretory response to glucose and progressive glucose intolerance. Third, primary islets and beta-cell lines derived from IRS-1 knockout mice show reduced insulin content and blunted secretory responses to multiple stimuli, and IRS-2 knockout mice manifest a defect in beta-cell development. These data indicate the presence of an insulin-signaling pathway in the islets/beta-cells potentially linked to glucose signaling that plays an important role in islet function. The goals of this proposal are to understand the mechanisms by which the insulin-signaling proteins modulate beta-cell function and to delineate the cross-talk between the insulinand glucose-signaling pathways. Our studies will be directed at the following specific aims: 1) to identify the cellular mechanisms by which proteins in the insulin-signaling pathway modulate insulin secretion and synthesis in response to different stimuli, 2) to determine the alterations in glucose metabolism in islets/beta-cells isolated from mice lacking the IR and the IRS proteins and to study the effects of re-expression of the proteins in the knockout cell lines, and 3) to evaluate the expression of insulin signaling proteins and glucose metabolism in islets isolated from rodent models of diabetes. My earlier training in islet physiology and metabolism and the experience I am currently gaining as a research fellow at the Joslin Diabetes Center have provided me with a unique perspective to explore the significance of the insulin signaling pathway in islet/beta-cell function. The mentoring support of Prof. Kahn and the academic environment of the Joslin Diabetes Center and Harvard Medical School provides me

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with an excellent opportunity to continue my investigation in type 2 diabetes and further develop my skills to attain my goals as an independent investigator. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INSULIN ACTION IN MUSCLE & FAT CELL Principal Investigator & Institution: Lawrence, John C.; Professor; Pharmacology; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904 Timing: Fiscal Year 2002; Project Start 01-APR-1981; Project End 31-MAR-2006 Summary: Insulin lowers blood glucose by stimulating glucose uptake and storage in various target tissues, the most important being liver, skeletal muscle, and fat. The failure to respond appropriately to insulin results in a rise in blood sugar. Type II diabetes mellitus develops if beta cells become unable to release enough insulin to compensate for the insulin resistance. Determining the processes involved in the normal response to insulin will be essential for understanding insulin resistance, and the overall objective of this project is to define mechanisms involved in the actions of insulin in skeletal muscle and fat cells. Initial aims are to investigate the stimulation of glycogen synthesis by insulin. This effect is of particular importance in the control of blood glucose levels, as most of the glucose taken up following a meal is deposited as glycogen in skeletal muscle. Experiments in Aim 1 are proposed to investigate both the mechanism through which insulin activates glycogen synthase (GS), the enzyme that synthesizes glycogen from uridine diphosphoglucose (UDPG), and the importance of increasing GS activity in the stimulation of glycogen synthesis. Treating rats with insulin results in a marked decrease in muscle UDPG, implying that the activity of UDPG pyrophosphorylase (PPL) may limit the rate of glycogen synthesis. Objectives of Aim 2 are to determine whether UDPG PPL is subject to hormonal and/or metabolic control, and to investigate the potential limiting role of UDPG PPL in glycogen synthesis in rodent and human muscles. In the last two Aims we will investigate new targets of insulin action. We have recently discovered an adipocyte protein, designated betaip140, which is phosphorylated in response to insulin and coimmunoprecipitates with the beta isoform of protein kinase B (PKB). By purifying betaip140 and sequencing peptides by tandem mass spectrometry, we have shown that betaip140 is the product of the Kiaa0188 gene, recently identified by genetic fine mapping as a candidate gene for the fld mouse phenotype. Mice homozygous for the fld gene exhibit insulin resistance, glucose intolerance, and markedly diminished adipose tissue mass. Aim 3 is to investigate the potential interactions between betaip140 and PKBbeta, to define the mechanisms controlling betaip140 phosphorylation, and to determine the role of betaip140 in insulin action. Many other proteins that are phosphorylated in response to insulin can be detected, but have not been identified. This represents a serious gap in our understanding of insulin action, since at least some of the proteins are likely to represent downstream targets that are involved in the important metabolic responses to insulin. The objective of Aim 4 is to identify these new targets. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: INSULIN AND THE POLYCYSTIC OVARY SYNDROME Principal Investigator & Institution: Nestler, John E.; Professor and Chairman; Internal Medicine; Virginia Commonwealth University Richmond, Va 232980568 Timing: Fiscal Year 2002; Project Start 01-AUG-1997; Project End 31-JUL-2005 Summary: The polysystic ovary syndrome (PCOS) is a poorly understood disorder that affects approximately 6-10 percent of women of reproductive age. PCOS is characterized

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Glucose Intolerance

by hyperandrogenism and chronic anovulation, and is the leading cause of female infertility in the United States. Women with PCOS are also at high risk for developing type 2 diabetes, presumably due to the insulin resistance that accompanies the syndrome. Our long-term goal is to elucidate the relationship between insulin resistance and PCOS, especially as it relates to hyperandrogenism. Some actions of insulin may be effected by putative inositolphosphoglycan (IPG) mediators of insulin action and a deficiency in a specific D-chiro-inositol-containing IPG may contribute to insulin resistance in individuals with impaired glucose tolerance or type 2 diabetes. Our studies indicate that D-chiro-inositol (DCI) administration improves glucose intolerance while reducing circulating insulin in women with PCOS, and is also associated with decreases in serum androgens and improved ovulatory function. In addition, our in vitro studies in human thecal cell cultures suggest that the IPG signaling system plays a role in transducing insulin's stimulation of ovarian androgen biosynthesis. These studies have led us to focus our short- term goals on an assessment of the role of the IPG signaling system in PCOS, and pursue a unifying hypothesis to explain the above experimental observations. Our hypothesis is that women with PCOS are DCI deficient, perhaps related to an intracellular defect in the conversion of myo-inositol (MYO) to DCI. This results in a decrease in a DCI-containing IPG mediator (DCI-IPG) and an increase in a MYO-containing IPG mediator (MYO-IPG) bound to the outer leaflet of the cell membrane. We further propose that the resulting deficient insulin-mediated release of DCI-IPG contributes to insulin resistance in PCOS, whereas the simultaneous hyperinsulinemia mediated increased release of MYO-IPG at the level of the ovary acts to stimulate ovarian androgen biosynthesis. If our proposed studies confirm a role for IPG's in insulin resistance and hyperandrogenism of PCOS, they will substantially enhance our understanding of the disorder's pathogenesis and are likely to provide insights into novel treatment strategies directed specifically at the IPG system and normalization of its function. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INSULIN MEDIATED GLUCOSE TRANSPORT DISRUPT BY ETHANOL Principal Investigator & Institution: Nagy, Laura E.; Associate Professor; Nutrition; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2002; Project Start 01-APR-1998; Project End 31-MAR-2003 Summary: (Adapted from the investigator's abstract). Epidemiological studies have identified alcohol consumption as an independent risk factor for the development of non-insulin dependent diabetes mellitus (NIDDM). Moreover, both short and long-term ethanol consumption result in glucose intolerance in humans and rats. However, the mechanism(s) for this disruption of glucose homeostasis by ethanol is not well understood. Since adipose and skeletal muscle are major sites for both insulin action and glucose disposal, the applicants have investigated the effects of ethanol on insulinmediated control of glucose transport in adipocytes and skeletal muscle from rats. Ethanol feeding to rats for four weeks decreased insulin-stimulated glucose uptake in adipocytes and soleus, a red oxidative muscle, but had no effect on uptake in the epitrochlearis, a white glycolytic muscle. Decreased uptake in the adipocyte was associated with an impairment in translocation of GLUT4 from intracellular vesicles to the plasma membrane. Total GLUT4 protein was also reduced after ethanol feeding; as in other model systems, decreased GLUT4 was associated with an increase in G alpha s and cAMP production in the adipocyte. The major goals of this proposal will be to determine whether ethanol impairs insulin-stimulated glucose uptake in red, oxidative

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muscle and adipocytes by: (1) disrupting insulin receptor mediated signal transduction and/or (2) impairing the ability of GLUT4 vesicles to dock and fuse with the plasma membrane. The effects of ethanol on early events in insulin signalling (insulin receptor substrate-1 phosphorylation and activation of phosphotidylinositol-3-kinase) which lead to translocation of GLUT4 will be measured. The applicants will also investigate the effects of ethanol on the intracellular distribution of GLUT4 protein after insulin stimulation, as well as the distribution of vesicular proteins involved in GLUT4 vesicle trafficking. Investigation of the mechanisms for ethanol-induced insulin resistance is critical for understanding the interaction between alcohol consumption and the development of NIDDM. Such an understanding will foster the development of strategies to either prevent or reverse the long-term effects of ethanol on glucose homeostasis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: JAPANESE AMERICAN COMMUNITY DIABETES STUDY Principal Investigator & Institution: Boyko, Edward J.; Professor; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2002; Project Start 01-DEC-2001; Project End 30-NOV-2002 Summary: This longitudinal study examines the relationship of environmental factors in the development of the insulin resistance syndrome (hyperinsulinemia, central obesity, glucose intolerance, hypertension, dyslipidemia, and coronary heart disease) in Japanese Americans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: KETONE DYSREGULATION AND MUSCLE INSULIN RESISTANCE Principal Investigator & Institution: Muoio, Deborah M.; Medicine; Duke University Durham, Nc 27710 Timing: Fiscal Year 2004; Project Start 01-JUL-2004; Project End 30-JUN-2008 Summary: (provided by applicant): Compelling evidence links the development of muscle insulin resistance to fatty acid (FA) oversupply, but there is still uncertainty regarding which specific FA metabolite(s) and regulatory pathways are directly responsible for mediating insulin desensitization. Our current knowledge is based largely on a candidate molecule approach in which the selection of potentially relevant lipid metabolites relies heavily on implicit biases or availability of specific assays. To overcome this obstacle, we have employed mass spectroscopy-based metabolic profiling to comprehensively evaluate multiple lipid-derived metabolites in muscle from rats made insulin resistant by a high fat diet compared to controls. This unbiased "metabolomics" approach led to our discoveries that insulin resistant rats exhibit marked intramuscular accumulation of the ketone, beta-hydroxybutyrate (betaHB), at least a portion of this accumulated ketone was synthesized directly in the muscle tissue, and that genetic manipulations that restored insulin sensitivity corresponded with a 55% decrease in muscle (HB levels. These exciting findings implicate muscle ketone dysregulation as a causal factor in the etiology of lipid-induced insulin resistance. Previous research supports an inverse correlation between ketogenesis and glucose intolerance, but no consideration has been given to the possibility that dysregulated metabolism of ketones within muscle tissue could contribute to insulin resistant states. We hypothesize that chronic high fat feeding and/or overnutrition imposes a state of persistent and abnormal ketogenesis in skeletal muscle, which in turn plays a direct role in causing maladaptive changes in glucose handling and insulin sensitivity. We propose

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to test these hypotheses with the following specific aims: 1) To determine whether ketone dysregulation is a common feature in multiple animal models of insulin resistance. This will be done by profiling gene expression and metabolic markers of ketone metabolism in rodent models of obesity and diabetes. 2) To determine whether perturbing ketone metabolism (by FA overexposure or by adenovirus-mediated delivery of ketogenic genes), disrupts glucose handling and insulin signaling in isolated muscles and/or muscle cells in culture. 3) To determine whether adenovirus-mediated overexpression of genes that suppress ketogenesis and/or enhance ketone degradation in muscle can reverse diet-induced insulin resistance in vivo. The results from these studies are expected to yield important new insights into the mechanism of FA-induced insulin resistance in skeletal muscle, with potential therapeutic implications for treatment of type 2 diabetes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: LEPTIN AND PERIPHERAL GLUCOSE METABOLISM Principal Investigator & Institution: Harris, Ruth B.; Associate Professor; Foods and Nutrition; University of Georgia 617 Boyd, Gsrc Athens, Ga 306027411 Timing: Fiscal Year 2002; Project Start 01-MAR-1999; Project End 28-FEB-2004 Summary: Leptin is a protein produced by adipose tissue and hypothesized to be a circulating lipostatic factor (82). Our preliminary data shows that leptin infusion into normal mice inhibits insulin release in response to a glucose challenge, induces insulin resistance in adipocytes, but promotes insulin-stimulated glycogen synthesis in muscle. An impaired acute insulin release in response to glucose is a risk factor for development of non-insulin dependent diabetes (NIDDM) (25) and increased insulin-stimulated glycogen synthesis in muscle is characteristic of the early metabolic changes observed during the development of insulin resistance in high-fat fed rats (48). We hypothesize that leptin mediates development of an impaired glucose tolerance that precedes early NIDDM by suppressing glucose stimulated insulin release and modifying insulinstimulated glucose utilization in a tissue and pathway specific manner. Experiments described in Specific Aim 1 will examine the effects of leptin infusion on glucose and fatty acid metabolism of the three major insulin-responsive tissues in lean mice and will determine whether the effects on insulin responsiveness are mediated by the long-form leptin receptor, OB-Rb. Experiments in Specific Aim 2 will investigate the role of leptin in modifying insulin signaling to determine whether leptin changes tissue insulin receptor number, glucose transporter number or translocation, and insulin receptor tyrosine kinase activity. These processes represent the first stage of the insulin signaling cascade and the results of these experiments will determine how leptin modifies the initial stages of insulin signaling to change peripheral tissue glucose utilization. The studies described in this proposal will provide the information required to understand how leptin treatment modifies insulin responsiveness in peripheral tissues and the mechanisms by which this is achieved. It is essential to elucidate this aspect of leptin activity as it may account for the increased risk of development of glucose intolerance that is associated with obesity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: LIPODYSTROPHY AMONG HIV-INFECTED PATIENTS Principal Investigator & Institution: Crane, Heidi M.; Medicine; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2004; Project Start 01-AUG-2004; Project End 30-APR-2009

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Summary: (provided by applicant): CANDIDATE: Heidi M Crane, MD, MPH is currently completing an Infectious Disease Fellowship at the University of Washington. Her long-term interest in complications of HIV disease has developed into a specific interest in the epidemiology of metabolic complications among HIV-infected patients. ENVIRONMENT: The University of Washington represents an ideal environment for Dr Crane's training and for the research she proposes. World-renowned clinical and epidemiological expertise related to HIV and to metabolism are available to support the development of Dr. Crane's research career. RESEARCH: A dramatic decline in overall HIV-related morbidity and mortality has been accompanied by an increase in metabolic complications such as lipodystrophy. The syndrome of lipodystrophy consists of several body morphology abnormalities and is often associated with metabolic abnormalities such as dyslipidemia and glucose intolerance. Why some patients develop these complications and others do not is not understood. Dr. Crane proposes to study body morphology and metabolic abnormalities in a clinical cohort of approximately 1500 patients infected with HIV. This investigation will be facilitated by the University of Washington HIV Information System, a state-of-the art clinical and research database, and by the longitudinal collection of patient-completed measures of body morphology abnormalities, depression, and health-related quality-of-life. This study will examine the association between antiretroviral therapy, patient-related characteristics, and the development of body morphology and metabolic abnormalities. This study will also examine the association between body morphology abnormalities and health-related quality-of-life. Identification of factors that increase or decrease the likelihood of developing metabolic abnormalities may lead to changes in the clinical care of patients with HIV; to advances in understanding the mechanisms that lead to the development of these abnormalities; and ultimately to therapy for these complications. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: LONG-TERM FOLLOW-UP OF A PROSPECTIVE RANDOMIZED TRIAL OF SIROLIMUS AND TACROLIMUS Principal Investigator & Institution: Matas, Arthur J.; Professor; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2008 Summary: Our objectives are to determine the best long-term immunosuppression protocol for kidney transplant recipients on a steroid-free regimen. Steroids are associated with numerous side effects posttransplant including osteoporosis, avascular necrosis, fractures, cataracts, hypertension, glucose intolerance, and appearance and mood changes. And it is recognized that side effects lead to noncompliance; in transplantation, noncompliance reads to increased rejection and graft loss. We and others have shown that kidney transplants can be successfully done with either complete avoidance or rapid discontinuation of steroids. We will compare long-term outcome of 3 immunosuppressive protocols, all using antibody induction and rapid discontinuation of prednisone: cyclosporine and mycophenolate vs. high (blood) level tacrolimus and low level sirolimus vs. low (blood) level tacrolimus and high level sirolimus. Our main end points will include patient and graft survival, incidence of biopsy-proven chronic allograft nephropathy, and renal function. We will also determine the incidence of complications and the long-term costs of the individual protocols. We will be able to determine whether or not one of these clinical care protocols provides better outcome for kidney transplant recipients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MECHANISM OF GLUCOSE INTOLERANCE PREADOLESCENT/ADOLESCENT CHILDREN WITH IDDM

IN

Principal Investigator & Institution: Tamborlane, William V.; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2003 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MECHANISMS OF ACTION IN DPP INTERVENTIONS Principal Investigator & Institution: Kitabchi, Abbas E.; Professor; Medicine; University of Tennessee Health Sci Ctr Memphis, Tn 38163 Timing: Fiscal Year 2001; Project Start 05-AUG-1998; Project End 30-JUN-2005 Summary: (adapted from the application) The Diabetes Prevention Program (DPP) is an NIH-sponsored multicenter study with the specific objective of comparing, in high risk individuals, the efficacy of three intervention methods (intensive behavior modification, metformin, and troglitazone) vs control placebo group in preventing or delaying conversion of impaired glucose tolerance (IGT) to non-insulin dependent diabetes mellitus (NIDDM). A total of 4000 subjects (from 26 clinical centers) of whom 50% will consist of minority groups, will be randomly assigned to one of the four groups. Since the DPP is not designed to study the mechanism of action of these interventions, the present proposal is an ancillary study to the DPP to investigate the mechanisms by which the three interventions affect glucose intolerance and insulin resistance. Other rationales for the proposed study are that: (a) hyperandrogenism and decreased sex hormone binding globulin (SHBG) are known to be additional risk factors for development of NIDDM in certain female populations, (b) hyperandrogenism of gonadal origin [i.e. testosterone(T), and androstenedione(A)] is believed to be more deleterious to glucose tolerance and insulin sensitivity than adrenal androgens [i.e. DHEA(D) DHEAS(DS)] and c) recent preliminary studies suggest that metformin, troglitazone and exercise plus dietary modification alter androgenic profiles and improve glucose intolerance, possibly by three different mechanisms. Therefore, the DPP offers a unique opportunity to study the mechanism of action of these three interventions. We hypothesize that those modalities which most improve glucose intolerance and insulin resistance will be associated with more favorable androgenic profiles (i.e. lower T/D ratio) and CV risk factors. The specific aim of this ancillary study is to recruit 200 pre- and perimenospausal women from eight of the DPP centers (equally distributed among the four treatment groups) and among three ethnic groups (Caucasians, Hispanics and African-Americans) to: (a) assess insulin secretion by OGTT, (b) measure androgenic profiles, (c) measure body fat distribution by CT Scan, and lean body mass (LBM) and fat content by DEXA and (d) study glucose and insulin metabolism and clearance, and insulin sensitivity by the use of modified frequently sampled iv glucose tolerance test (FSIGT). These studies will be done at baseline, and at the end of the 1st and 3rd year of intervention. The proposed ancillary study should, therefore, enable us to assess the correlation between glucose intolerance, insulin resistance, and androgenic profile, as well as the effect of various treatment modalities on them and the mechanism of action, in a setting of multiethnic diabetes prevention program. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MECHANISMS OF INSULIN RESISTANCE IN GDM Principal Investigator & Institution: Friedman, Jacob E.; Associate Professor of Pediatrics; Pediatrics; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 28-FEB-2007 Summary: (provided by applicant): Gestational Diabetes Mellitus (GDM) complicates up to 10% of all pregnancies and results in fetal hyperinsulinemia, macrosomia, and maternal complications during delivery. The morbidity to the mother and fetus does not end after pregnancy as recent data demonstrate a higher risk of obesity and glucose intolerance in adult offspring from GDM women and extremely high risk for type II DM in former GDM women. Our human studies have shown that a major defect in GDM involves the inability of insulin to stimulate glucose transport into skeletal muscle. The mechanisms for this severe insulin resistance are unknown, but likely involve a defect in the insulin receptor, IRS-1, and an unknown post-receptor defect at the level of GLUT4 translocation. The long-term goal of this project is to elucidate the underlying molecular signaling mechanisms that provoke insulin resistance in women with GDM. In this proposal we will dissect the roles of hormones of pregnancy, including TNFalpha, as negative regulators of insulin signaling, with a special emphasis on mechanisms for serine phosphorylation of IR and IRS-1 using human muscle fibers and L6 myotubes. Specific Aim 1 will test the hypothesis that re-distribution of PI 3-kinase to the insulin receptor mediates insulin resistance in pregnancy by triggering increased serine kinase activity to inhibit IRtyrosine phosphorylation and trigger IRS-1 degradation. In Specific Aim 2, we will determine how placental derived hormone(s) down-regulate IR and IRS-1 signaling using L6 muscle cells. In Specific Aim 3, we will investigate the contribution of skeletal muscle TNFalpha production as a mechanism for greater insulin resistance in women with GDM. In Specific Aim 4, we will explore the role of the novel CAP/Cbl signaling pathway as a potential mediator of GLUT4 translocation independent of PI 3-kinase. The outcome of these studies will provide important new insights into how pregnancy triggers insulin resistance in human skeletal muscle, and novel mechanisms for the down-regulation of insulin signaling. Ultimately, these studies should provide us with a better understanding of the cellular factors that trigger human GDM. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MECHANISMS OF THE GLUCOSE INTOLERANCE OF AGING Principal Investigator & Institution: Ader, Marilyn; Associate Professor; Physiology and Biophysics; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033 Timing: Fiscal Year 2002; Project Start 02-DEC-1998; Project End 30-NOV-2002 Summary: Impaired glucose tolerance is a hallmark of aging even in the absence of attendant pathology, and is associated with increased mortality due to enhanced risk for development of diabetes and cardiovascular disease. Intolerance of aging is typically attributed to the development of insulin resistance, resulting from changes in adiposity, diet, and/or sedentary lifestyle, and studies to understand the pathogenesis of intolerance have focused on the relative contributions of insulin resistance and pancreatic islet dysfunction. We have demonstrated that insulin-independent mechanisms of glucose regulation are equally important in determining glucose tolerance. These processes, termed "glucose effectiveness", are defined as the actions of glucose to regulate its own utilization (Rd) and hepatic production (HGO) independent

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of elevated insulin. The purpose of this proposal is to examine the role of glucose effectiveness in the glucose intolerance of normal, non-diseased aging in the rat. We will test the hypothesis that in insulin-resistant states such as aging, efficient disposition of a carbohydrate challenge becomes increasingly dependent on metabolic factors which are independent of insulin action, i.e. glucose effectiveness. These studies will establish the role of glucose effectiveness in the glucose intolerance of normal, non-diseased aging. We will apply newly developed methods to quantify glucose effectiveness directly in young and old rats, and determine how aging alters the relative contributions of Rd vs HGO and the specific tissue sites and glucose transporters involved. We will examine the mechanisms by which glucose effectiveness may compensate in agingassociated insulin resistance. Finally, we propose to examine the ability of caloric restriction to improve tolerance through their actions on glucose effectiveness, and determine the tissue sites, mechanisms, and glucose transporters which may be involved. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MENTORED DEVELOPMENT AW

PATIENT-0RIENTED

RESEARCH

CAREER

Principal Investigator & Institution: Gater, David R.; Assistant Professor; Phys Med and Rehabilitation; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002; Project Start 29-SEP-2000; Project End 31-AUG-2005 Summary: (Adapted from the applicant's abstract): SCI predispose to glucose intolerance and insulin resistance, presumably due to changes in body composition and skeletal muscle dysfunction, placing SCI individuals at greater risk for diabetes and coronary artery disease. In the able-bodied, marked improvements in glucose tolerance have been reported in response to aerobic exercise, with variable changes in insulin sensitivity. Resistance training has also improved glucose tolerance, and to a greater extent, insulin sensitivity in the able-bodied. Exercise responses in SCI have not been examined as extensively as they have in the general population, and yet this population has significantly more to gain than the able-bodied population by improving metabolic and functional abilities. The proposed hypothesis is that aerobic exercise, resistance training and/or a combination of aerobic exercise and resistance training will improve body composition and glucose tolerance, but only exercise which involves resistance training, and subsequent increases in muscle mass, will significantly improve insulin sensitivity in individuals with SCI. Twenty individuals with motor complete T6-L2 SCI will be recruited each year to participate in one of the following exercise protocols. Subjects will be randomly assigned to control or aerobic (Trial 1), resistance (Trial 2), and combined (Trial 3) exercise groups. Glucose tolerance, insulin sensitivity and body fat will be determined before and after each of the exercise interventions. If glucose intolerance and subsequently diabetes mellitus can be prevented in individuals with SCI by utilizing appropriately dosed exercise, significant savings in health care dollars and improved quality of life could be realized. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MELATONIN

METABOLIC

CHANGES

DURING

AGING:

A

ROLE

FOR

Principal Investigator & Institution: Rasmussen, Dennis D.; Research Associate Professor; Psychiatry and Behavioral Scis; University of Washington Grant & Contract Services Seattle, Wa 98105

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Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 30-JUN-2004 Summary: (provided by applicant) Adiposity, especially intra-abdominal adiposity, commonly increases by middle age in humans, non-human primates and rats, as do plasma insulin and leptin. These aging-associated increases in adiposity, insulin and leptin levels are associated with detrimental metabolic consequences, such as glucose intolerance, insulin resistance, diabetes, dyslipidemia, hypertension and cardiovascular disease. This spectrum of disorders, commonly grouped together as the "metabolic syndrome," is responsible for considerable aging-associated progressive pathology. Conversely, nocturnal pineal melatonin secretion decreases with aging in humans, other primates and rats. The proposed investigation evolves from our ongoing work demonstrating that chronic daily nocturnal administration of melatonin to middle-aged and older rats to produce youthful plasma melatonin levels and restore full amplitude circadian rhythmicity of plasma melatonin exposure also restored intra-abdominal adiposity, plasma insulin and plasma leptin to youthful levels. Administration of melatonin to young rats did not alter any of these parameters, suggesting that these responses were dependent upon the aging-associated decline in endogenous melatonin secretion. If melatonin supplementation to primates exerts these same effects, appropriate melatonin treatment could potentially provide effective prophylaxis or therapy for significant progressive pathologies associated with aging. Although indirect evidence suggests that melatonin may indeed play a role in regulating metabolism, body weight and adiposity in primates, a cause-effect relationship remains to be demonstrated. Testing this hypothesized relationship in middle-aged rhesus monkeys is the sole specific aim of the proposed investigation. A single study will be conducted, utilizing daily nocturnal intravenous melatonin vs. control infusions in unanesthetized and freely-moving middle-aged rhesus monkeys bearing indwelling vascular catheters protected by tethers. If chronic daily nocturnal melatonin treatment does decrease the monkeys' body weight, abdominal adiposity, plasma insulin, and/or insulin sensitivity to more youthful levels, the results of this investigation will justify and facilitate subsequent investigations to resolve mechanisms and clinical utility of these responses. Development of a therapy or preventive treatment that would attenuate or reverse the detrimental changes in carbohydrate and lipid metabolism which are commonly first expressed at middle age would reduce the progressive aging-associated morbidity which is the consequence of these conditions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: METABOLIC SYNDROME IN ADULT SURVIVORS OF CHILDHOOD ALL Principal Investigator & Institution: Gurney, James G.; Associate Professor; Pediatrics; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2004; Project Start 15-JUL-2004; Project End 30-JUN-2006 Summary: (provided by applicant): Treatment for acute lymphoblastic leukemia (ALL), the most common malignancy of childhood, involves 24 to 36 months of chemotherapy and high dose steroids. Additionally, cranial radiation is sometimes included for treatment or prevention of central nervous system involvement. The 5-year survival probability of childhood is all over 80%, and there are tens of thousands of adult survivors worldwide. These individuals have a higher than expected frequency of obesity and early mortality from cardiovascular disease. Childhood ALL survivors may also be at increased risk for the metabolic syndrome, a constellation of disorders characterized by central obesity, insulin resistance, glucose intolerance, dyslipidemia, and hypertension. The syndrome is clearly associated with substantially elevated risks

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for type 2 diabetes mellitus and atherosclerotic coronary disease. Deficiency in growth hormone secretion, which can result from damage to the hypothalamic-pituitary axis from either chemotherapy or cranial radiation, has been implicated in the pathogenesis of metabolic syndrome in childhood cancer survivors. 75 adult survivors of childhood ALL, ages 18-49 years will be randomly selected and recruited from an ongoing epidemiologic study to participate in a 2-day clinical evaluation. The aims of this study are to: 1) compare the extent to which prevalence of the metabolic syndrome is higher in ALL survivors than in same age, same sex population norms; 2) evaluate the relation between growth hormone deficiency and the metabolic syndrome; 3) investigate whether endothelial impairment and other early signs of cardiovascular disease are more prevalent among ALL survivors with, versus without, the metabolic syndrome; and 4) compare whether adjuvant cranial radiation increases risk for the metabolic syndrome above that of chemotherapy alone. A comparative evaluation of health behaviors and health knowledge related to diabetes, cardiovascular disease, physical activity, and nutrition, and will also be included in the study. This proposal addresses the great need for clinical research on long-term, adverse effects of childhood cancer and its treatment, particularly those that are preventable or modifiable. The study will provide important data on potential etiologic factors, such as growth hormone deficiency and cranial radiation, and on potential avenues for education and intervention, such as targeted modifications of physical activity and dietary habits. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MULTICENTER NETWORK OF MATERNAL-FETAL MEDICINE UNITS Principal Investigator & Institution: Carpenter, Marshall W.; Director, Maternal Fetal Medicine, Assoc; Women and Infants Hospital-Rhode Island 101 Dudley St Providence, Ri 029052499 Timing: Fiscal Year 2002; Project Start 03-APR-2001; Project End 31-MAR-2006 Summary: (provided by applicant): WIH and the Department of Obstetrics and Gynecology at Brown University School of Medicine have the capability to participate actively as a new member of the Cooperative Multicenter Maternal-Fetal Medicine Units Network. WIH operates one of the nation?s larger obstetrical services. All obstetric care is supported by insurance in Rhode Island. Consequently, the State?s ethnic and racial diversity is reflected among both private and clinic patients. Providing care to 74 percent of the State s patients, WIH s demographic and clinical statistics wholly reflect those of Rhode Island. During fiscal year 1999, 9023 deliveries were performed at WIH, 2099 among WIH Clinic and Maternal-Fetal Medicine patients. Of the total WIH deliveries, 174 had ruptured membranes before 35 weeks, 556 delivered prior to 35 weeks, 207 had multi-fetal pregnancies, 179 had gestational or chronic diabetes, 794 had hypertensive disorders in pregnancy, 539 had asthma or other respiratory disease and 163 had cardiac or vascular disease. The academic faculty and private practice community have had a consistently collaborative relationship providing access to the entire obstetrical population for cohort studies. Consequently, WIH is particularly suited for performance of clinical trials. The Maternal-Fetal Medicine Division is composed of six board-certified and one active candidate for the Maternal-Fetal Medicine boards, all of whom will support Network research protocols. The Division also employs two research nurses and a sonographer, all presently supported by NICHD funding, and three additional clinical nurses, all with extensive experience in cohort research. The Division has successfully enlisted patients (53-100 percent enlistment rates) in complex tocolysis trials and exercise, and metabolic and

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hemodynamic cohort studies with retention rates of 79-93 percent. The Division has maintained strong clinical and investigational relationships with local and regional private obstetricians, reflected in the proportions of private patients in Divisional cohort studies of 54-80 percent. The Division is presently engaged in three multicenter cohort studies funded by NICHD. It was selected by the Network in April 2000 to participate in the Beneficial Effects of Antenatal Magnesium (BEAM) Study to increase patient enlistment in this protocol and is presently beginning to enroll subjects. The Division has been funded as one of five North American sites in an international study of the maternal and perinatal impact of maternal glucose intolerance, the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) Study. The Division is also a participant in the First and Second Trimester Evaluation of Risk (FASTER) Study examining combined biochemical and sonographic first trimester screening for Down syndrome. WIH and the Maternal-Fetal Medicine Division will enlist subjects for all Network protocols and actively participate in proposing, planning and executing Network studies. Local infrastructure available for participation in multicenter clinical trials at WIH include (1) a large patient volume and highly involved full-time and voluntary obstetrical faculty; (2) robust clinical patient, laboratory, anatomic pathology, and pharmacy databases; (3) a strong history of collaboration between Maternal-Fetal Medicine and Neonatology Divisions; (4) decades-old perinatal tissue samples and anatomic pathology; and (5) a strong Departmental commitment to outcomes research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MUSCLE LACTATE PRODUCTION IN SEPSIS Principal Investigator & Institution: James, J H.; Res Ass Prof; Surgery; University of Cincinnati 2624 Clifton Ave Cincinnati, Oh 45221 Timing: Fiscal Year 2002; Project Start 01-MAY-1997; Project End 31-MAR-2005 Summary: The long-term objective of this work is to understand the changes in metabolism in sepsis in order to improve the therapy of septic patients. Sepsis results in a hypermetabolic state in which many aspects of carbohydrate metabolism are abnormal: enhanced peripheral glucose uptake and utilization, hyperlactacidemia, increased gluconeogenesis, depressed glycogen synthesis, glucose intolerance and insulin resistance. Traditionally, high circulating lactate concentration has been interpreted as tissue hypoxia or mitochondrial dysfunction. However, therapy to improve tissue perfusion does not always prevent lactate accumulation. Current understanding of energy metabolism cannot explain persistent glycolysis by welloxygenated tissues. High epinephrine levels in sepsis may cause the characteristic changes in carbohydrate metabolism through stimulation of the Na+-K+ pump in skeletal muscle. The stimulation of glycogen breakdown and lactate production in muscle by epinephrine may be closely tied to stimulation of the Na+, K+-ATPase, implying that muscle energy metabolism takes place in separate glycolytic and oxidative compartments. ATP consumption by the Na+, K+-ATPase appears to be the primary influence on ATP production in the glycolytic compartment. This proposal aims to explore these relationships in greater detail, both in septic and nonsepticrats. Studies will combine in vivo and in vitro assessments of Na+-K+ pump activity, membrane recruitment, glycolysis, glycogenolysis, ATP content and membrane permeability to Na+ and K+. The central role of epinephrine in sepsis-induced metabolic derangements will be examined in two ways (i) chronic infusion of epinephrine using implantable minipumps and (ii) chronic infusion of the beta-adrenergic blockers in sepsis. Studies in vitro will examine the persistence of epinephrine's effects on glycolysis and Na+, K+-

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ATPase activity after beta-blockade has occurred. Results of these studies will clarify metabolic relationships that are important both in health and disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MUSCLE-FAT COMMUNICATION AND METABOLIC IMPACT Principal Investigator & Institution: Phillips, Susan A.; Assistant Professor; Pediatrics; University of California San Diego La Jolla, Ca 920930934 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 30-JUN-2007 Summary: (provided by applicant): Obesity and diabetes are increasingly significant health care concerns. Type 2 diabetes (T2D), characterized by target tissue resistance to insulin and impaired pancreatic b-cell insulin secretion, affects 5-10% of the adult population. The amount of adipose tissue is highly correlated with and may contribute to insulin resistance. Obesity affects over 20% of the population and more than 80% of type 2 diabetics are obese, suggesting that obesity may be of pathophysiological importance to subjects genetically prone to develop diabetes. Multiple lines of evidence have suggested an endocrine role of adipose tissue to modulate energy homeostasis and insulin sensitivity, other studies suggest the possibility of a dynamic "cross-talk" relationship between muscle and fat. As skeletal muscle is the principal tissue of insulin mediated glucose disposal and the major site of peripheral insulin resistance in type 2 diabetics, these data give rise to the hypothesis that adipocyte endocrine dysfunction can result in glucose intolerance and insulin resistance in skeletal muscle. The longterm goal of this proposed study is to understand the communication between fat and muscle tissue in T2D. This study aims to determine 1) if fat from diabetic subjects contributes to the development of insulin resistance in skeletal muscle, and 2) if metabolic disturbances present in skeletal muscle from diabetic subjects alters the metabolic behavior of adipose tissue. Specifically we will use adipose and skeletal muscle biopsy tissue and cultured cells from diabetic and control subjects to ask: 1) what is the metabolic behavior of isolated adipocytes or myocytes in culture and how is it altered when their physiologic proximity is restored in culture? 2) What is the effect of T2D on the metabolic behavior of these tissues and is fat-muscle communication altered when proximity is re-established in culture? 3) Can treatment of either tissue alone with anti-diabetic thiazolidinediones alter the nature of the communication between these tissues when their physiologic relationship is restored in culture? Studying fat-muscle communication will enhance our understanding of the molecular mechanisms underlying obesity-diabetes syndromes, and may suggest new treatment strategies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NIDDM PRIMARY PREVENTION TRIAL (DPP-2) Principal Investigator & Institution: Kahn, Steven E.; Medicine; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2002; Project Start 20-AUG-1994; Project End 30-JUN-2003 Summary: Non-insulin dependent diabetes mellitus (NIDDM) affects approximately 7% of the United States population, with certain population group being at increased risk of developing the disease. NIDDM is preceded by a phase of impaired glucose tolerance (IGT) and consequently individuals with IGT are at increased risk of future NIDDM. In addition to subjects with IGT, women with a history of gestational diabetes mellitus (GDM) represent a group at high risk of subsequent NIDDM. The primary specific aim of the present proposal is to determine whether subjects with IGT or newly diagnosed NIDDM can have the progression of their glucose intolerance slowed or even reversed.

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A second aim of the study is to determine the importance of factors such as insulin resistance, insulin secretion and body fat distribution in predicting individuals who are likely to respond to an intervention aimed at slowing or reversing the progression to hyperglycemia. To address these issues, we propose to study 2 populations at increased risk of developing NIDDM. We will recruit 100 Asian-Americans and 100 women with a history of GDM as part of a multicenter national study. Newly diagnosed NIDDM subjects (with a fasting plasma glucose < 140 mg/dl), identified during the screening program, will also be studied. Subjects from each population will be randomized into 4 groups: a control group, a group undertaking diet and exercise modifications, a group receiving medication (glipizide), and a group receiving diet and exercise modification and medication. Subjects will undergo these interventions for a minimum 4 year period and during this time will have sequential measurements of glucose tolerance performed. This randomization scheme allows for factorial design and analysis. In addition, measurements of body fat distribution, insulin sensitivity, insulin secretion, lipid measurements, resting metabolic rate, maximal oxygen uptake, and quality of life will be made. The data obtained from this study will answer whether the above intervention strategies in subjects at high risk of developing NIDDM and/or in subjects with recently diagnosed NIDDM, can slow or reverse the deterioration in glucose metabolism that is commonly seen in these individuals. The results of this study will have implications for future public health strategies in the United States and world-wide. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NIDDM PRIMARY PREVENTION TRIAL (DPT 2) Principal Investigator & Institution: Pi-Sunyer, F Xavier.; Director; St. Luke's-Roosevelt Inst for Hlth Scis Health Sciences New York, Ny 100191102 Timing: Fiscal Year 2002; Project Start 15-AUG-1994; Project End 14-APR-2003 Summary: The specific aims of this proposal are two-fold: the first aim is to conduct a multi-center, randomized clinical trial to evaluate the efficacy of intervening to delay or prevent the onset of non-insulin dependent diabetes mellitus (NIDDM) in individuals at increased risk of NIDDM. These individuals will consist of persons with impaired glucose tolerance (IGT) and persons with a previous diagnosis of gestational diabetes mellitus (GDM) who now have IGT. The second aim is to conduct a multi-center, randomized clinical trial to evaluate the efficacy of intervening to prevent the deterioration of previously undiagnosed NIDDM (early, asymptomatic NIDDM found during screening). All subjects will be identified by screening. At least 50% of the sample will be minority. The individuals in the first group will be those with IGT. Individuals in the second group will be those with newly diagnosed NIDDM. Criteria will be set to take only mild NIDDM for the trial, the more severely compromised patients will be referred for treatment. Individuals in both groups will be randomized into an Experimental and a Control Group. Intervention for the Experimental Group will consist of two Levels. Level I will be initiated first and will be a diet, exercise, and behavior modification program. Level II, pharmacological intervention with metformin, will be added in Level I is unsuccessful. Intervention in the Control Group will only be contact every 6 months for glucose testing. Subjects will be followed for 5 yrs with periodic testing for glucose intolerance. The major end point will be the 2 hr post glucose venous plasma. value. Twenty sites will serve as Centers and each site will enroll 98 patients. Each site will emphasize one or two racial/ethnic groups. Our Center will plan to study Caucasian and Black volunteers, although we could also study Hispanics if the protocol writers wished us to do so. There will be an initial planning phase of 1 yr, a clinical trial phase of 5 yrs, and a close-out phase of 1 yr. There will be a

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Data Coordinating Center that will collect all data and will be in charge of the central clinical laboratory. Our Center has the appropriate population base for both the IGT and the GMD parts of this clinical trial and well-trained, experienced personnel for carrying out the protocol. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PATIENT RECRUITMENT & CLINICAL MANAGEMENT CORE Principal Investigator & Institution: Powderly, William G.; Professor of Medicine; Internal Medicine; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2002; Project Start 30-SEP-2000; Project End 31-AUG-2005 Summary: (Adapted from the applicant's abstract) This proposal will establish a clinical core to recruit and retain HIV- infected subjects for the investigations proposed in the accompanying applications from Drs. Samuel Klein and Kevin Yarasheski. Suitable HIV subjects as well as those currently receiving treatment will be identified and recruited. This will include patients without prior antiretroviral therapy, as well as those receiving potent treatment - with or without protease inhibitors. Significant metabolic syndrome will be defined, for the purposes of these investigations as patients with an abnormal glucose intolerance, hypertriglyceridemia, and central adiposity. Patients with and without this syndrome will be recruited. Of paramount importance, will be subjects who are currently receiving protease-inhibitor based treatments who experience metabolic or other side-effects and who will choose to be switched to alternative regimens. The investigators from the clinical core will ensure that such switches are medically appropriate, maintaining viral suppression where possible using alternative potent antiretroviral regimens. Investigators from the clinical core will monitor patients both during the intensive investigations, and where relevant, during changes in antiretroviral therapy. The proposal projects that approximately twenty new patients can be enrolled in this clinical research each year, with a total enrollment target of 100 subjects. Research will be conducted in the University's General Clinical research center and at the clinics of the AIDS Clinical Trials Unit. We will match enrollment in trials to the demography of the epidemic in St. Louis. We therefore anticipate that at least 35% of enrollment will be from the African- American community and at least 10% will be women. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PERINATAL METABOLIC AND HORMONAL EFFECTS Principal Investigator & Institution: Devaskar, Sherin U.; Professor; Pediatrics; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2002; Project Start 01-JUL-1989; Project End 28-FEB-2006 Summary: (provided by applicant): Perinatal Origins of Adult Disease" describes various observations of adult consequences due to altered metabolic/hormonal milieu in-utero or postnatally. Examples include 1] infants born to diabetic mothers (IDM), who, independent of their genetic predisposition, develop obesity and glucose intolerance in later life, and 2J intra-uterine growth restricted infants (IUGR) who develop syndrome X consisting of insulin resistance, obesity, and dyslipidemia with hypertension and coronary artery disease during adult life. To decipher the mechanism(s) by which this phenomenon occurs, we first characterized two rat models: 1] the streptozotocin-induced maternal diabetes where the macrosomic, hyperinsulinemic newborn offsprings develop visceral obesity, hyperinsulinemia, and glucose intolerance as adults; and 2] the prenatally starved mother where the IUGR,

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hypoinsulinemic newborn offsprings also demonstrate visceral obesity, hyperinsulinemia, and glucose intolerance as adults. Next, we focused on the recently cloned "obesity (ob) gene product (leptin) that is predominantly synthesized by adipocytes, and plays a mitogenic role in promoting fetal growth. We noted that fetal hyperinsulinemia as seen in the IDM increases while hypoinsulinemia seen with IUGR decreases fetal leptin concentrations. In addition, circulating leptin concentrations increased in the adult obese and glucose intolerant offspring of a diabetic mother and IUGR offsprings. Recently, we have demonstrated that leptin administration during the postnatal period alters skeletal muscle uncoupling proteins causing a dose-dependent decline in body weight. Postnatal leptin administration also causes an imbalance in the rat hypothalamic orexigenic (neuropeptide Y, NPY) and anorexigenic (a-melanocyte stimulating hormone, a-MSH) neuropeptides, leading to persistent changes in food intake and body weight in the adult female rat progeny. This observation gives rise to the innovative concept of in-utero/postnatal leptin concentrations predetermining the adult phenotype by "the mechanism of hormonal/metabolic imprinting." Our overall hypothesis is that in-utero/postnatal leptin concentrations with or without altered metabolic substrate availability permanently alter the mechanisms regulating food intake and energy expenditure, thereby predetermining the ultimate adult phenotype. To test this hypothesis, we propose the following specific aim: To examine the effect of postnatal intracerebroventricular (ICV) versus systemic (IP) leptin administration on hypothalamic neuropeptides that regulate food intake, and uncoupling proteins (UCP) that mediate energy expenditure, both of which determine the net body weight gain pattern in 1] the normosomic offspring of a normal rat pregnancy, 2] the macrosomic offspring of a streptozotocin-diabetic rat mother, and 3] the IUGR offspring of a prenatally starved rat mother, at d3, d10, d21, d60, and d180 in males and females. The results of our studies will test the above stated hypotheses and determine the contribution of in-utero and postnatal "leptin" in modifying the mechanisms leading to the adult phenotype predetermined by in-utero metabolic perturbations. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PHENOTYPIC AND FUNCTIONAL CHARACTERIZATION OF BETA CELL* Principal Investigator & Institution: Verfaillie, Catherine M.; Professor; Medicine; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2002; Project Start 30-SEP-2001; Project End 31-JUL-2004 Summary: Type-1 diabetes is caused by progressive loss of insulin producing beta cells leading to glucose intolerance. Transplantation of allogeneic pancreas and, more recently, islets derived from allogeneic donors can result in reversal of glucose intolerance. However, the number of donor pancreases and/or islets that are available limits such therapy. However, the number of donor pancreases and/or islets that are available limits such therapy. Therefore, new strategies for beta cell replacement are needed. Despite recent advances in identification of mechanisms underlying beta cell development and beta cell function through targeted mutagenesis studies and immunohistochemical observation of the developing pancreas in purine or chicken embryos, our understanding of the mechanisms important for pancreatic islet development is still incomplete. Significant progress has been made in our understanding of the mechanisms important for pancreatic islet development is still incomplete. Significant progress has been made in our understanding of hematopoietic and neuronal stem cells, as well as multipotent embryonic stem (ES) cells and multipotent adult stem cells. However, the quest for identification of islet stem cells has

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been hampered by the lack of appropriate research tools including antibodies against stage-specific cell surface markers that will allow purification of viable progenitor and stem cells. Based on insights gained in the type of transcription factors responsible for islet differentiation, we will create mice genetically engineered to express fluorescent makers for specific developmental stages (HNF3- pdx1, Ngn3, Nkx6.1) that can be monitored in live cells derived from such mice. Sources for islet stem cells will include the pancreas proper, ES cells and adult tissue specific stem cells, which may be coaxed to acquire an islet fate. These three sources of cells from engineered "rainbow" mice will serve to: (1) identify islet stem cells and progenitor cells based on genetic, cell surface and functional characteristics; (2) study the function of genes known to be involved in endocrine pancreas specification and differentiation, and identify novel genes involved in pancreas development; (3) develop monoclonal antibodies against islet stem, progenitor and precursor cells; (4) develop selection methods to purify islet stem cells from three cell sources; (5) develop culture systems that will induce mature insulinproducing cell differentiation from islet stem ells ex vivo; and (6) demonstrate that islet stem cells from fetal tissue embryonal stem cells or multipotent adult stem cells have the ability to reverse diabetes in vivo. These studies will significantly advance our knowledge on the cell surface phenotype and expressed gene profile of islet stem and progenitor cells as well as the role of known and novel transcription factors in endocrine pancreas commitment and differentiation. They will also provide important cellular, antibody and genetic tools that will aid in the characterization of islet stem and progenitor cells. Finally, we will be in a position to determine whether islet stem cells, to be used for therapy of diabetes, can best be selected from the pancreas proper, from ES cells or from multipotent adult stem cells. These studies should then ultimately culminate in characterization of islet stem cell suitable for clinical therapy of diabetes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HEMEOSTASIS

PHOSPHODIESTERASE

REGULATION

OF

GLUCOSE

Principal Investigator & Institution: Michaeli, Tamar H.; Developmtl & Molecular Biology; Yeshiva University 500 W 185Th St New York, Ny 10033 Timing: Fiscal Year 2003; Project Start 15-MAR-2003; Project End 31-DEC-2006 Summary: (provided by applicant): The objective of the proposed research is to elucidate the contribution of the camp phosphodiesterase, PDE7A, to the regulation of glucose homeostasis. Since cAMP antagonizes insulin action, cAMP phosphodiesterases can augment insulin signaling by reducing levels of cAMP pools relevant to insulin action. In particular, PDE3B augments insulin signaling in fat and liver. PDE3B, however, is not expressed in skeletal muscle. Our studies established PDE7A as a cAMP specific phosphodiesterase expressed to high levels in skeletal muscle as the particulate PDE7A2 splice variant. Our targeted disruption of the PDE7A gene in mice yielded PDE7KO mice with defects in glucose homeostasis - glucose intolerance and insulin resistance. PDE7KO mice, however, are not hyperinsulinemic and their insulin secretion in response to injected glucose is indistinguishable from that of wild type mice. Consistent with the abundant expression of PDE7A2 in skeletal muscle, and with the strong contribution of skeletal muscle to whole body glucose disposal, PDE7KO mice are impaired in insulin stimulated glucose uptake by skeletal muscle, but not by adipose tissue. Based on these observations, we hypothesize that a primary defect in PDE7KO mice is the disposal of glucose by skeletal muscle. The experimental program will examine in vivo defects of PDE7KO mice in glucose disposal, glucose and lipid metabolism, cAMP and insulin signaling, in skeletal muscle, and in liver and adipocytes.

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The contribution of pancreatic beta-cells to PDE7KO phenotypes will also be assessed. Thus, the aim of the proposal is to at understand the cross talk between the insulin and the cAMP signaling pathways and mechanisms underlying diabetogenic, metabolic perturbations in glucose homeostasis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PHYSICAL ACTIVITY ON INSULIN RESISTANCE IN THE ELDERLY Principal Investigator & Institution: Evans, William J.; Professor; Geriatrics; University of Arkansas Med Scis Ltl Rock Little Rock, Ar 72205 Timing: Fiscal Year 2002; Project Start 30-SEP-2001; Project End 31-JUL-2004 Summary: (provided by applicant) Advancing age is associated with insulin resistance, glucose intolerance, and Type 2 diabetes. Regular higher-intensity aerobic exercise reduces insulin resistance and lowers the risk of Type 2 diabetes. Nonetheless, recent cross-sectional data, based on ACSM/CDC physical activity recommendations for moderate-intensity activity on most if not all days of the week (i.e., 1000 kcal/wk), demonstrate that insulin levels are lower with regular moderate-intensity activity in middle-aged adults, suggesting a reduction in insulin resistance. Despite these crosssectional data, few well-controlled prospective studies have determined if these recommendations are appropriate to reduce insulin resistance in the elderly. Because higher-intensity aerobic exercise is not practical for a large percentage of the elderly, data are needed to determine the efficacy of moderate-intensity exercise on reducing insulin resistance. Therefore, the primary aim of this study will be to examine the influence of 1000 kcal/wk of moderate versus higher-intensity aerobic exercise on insulin-simulated glucose disposal. A secondary aim will examine if moderate and higher-intensity aerobic exercise differentially influence non-exercising activity. Recent data in the elderly suggest that regular higher-intensity activities may reduce nonexercising activity during rest of the day. We will recruit 57, 65-90 y old women and men, who will be randomized into one of the following three groups: 1) Moderateintensity activity (1000 kcal/wk at 50 percent VO2peak; 2) Higher-intensity activity (1000 kcal/wk at 75 percent VO2peak); 3) Control. Subjects will complete 12 wk of aerobic cycling with pre and post-testing for insulin-stimulated glucose disposal via the hyperinsulinemic/euglycemic clamp, glucose tolerance by an OGTT, and body composition using dual energy x-ray absorptiometry. Physical activity levels will be assessed by structured questionnaire every 3 weeks. Our primary hypothesize is that 1000 kcal/wk of moderate or higher-intensity activity will be equally effective decreasing insulin resistance in the elderly. Our secondary hypothesis is that higherintensity activity will decrease non-exercising physical activity in the elderly. This New Investigator application will provide data to base future aerobic exercise recommendations in elderly adults. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PILOT STUDY--IL 6 GENOTYPES & FRAGILITY RISK IN ELDERLY Principal Investigator & Institution: Walston, Jeremy D.; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2008 Summary: (provided by applicant): The purpose of this study is to identify single or combinations of IL-6 gene variants that associate with elevations of serum IL-6 in the Women's Health and Aging I and II cohorts, and to determine the relationship between these genotypes, skeletal muscle strength, and the syndrome of frailty in the same

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group. The long term goal of this pilot study is to identify clinically relevant IL-6 variants and translate them into test that will identify those older adults at highest risk for losing independence through the development of frailty or its components. Another long-term goal is to develop further studies in order to determine if these clinically relevant gene variants can be markers for those at highest risk for disease complications and poor outcomes. IL-6 mediated chronic inflammation plays a role in the development of frailty in older adults through its contribution to the development of muscle mass and strength decline, glucose intolerance, and anemia. The etiology of this increase in some older adults and not others is multifactorial and includes increased prevalence of acute and chronic disease, declines in sex steroids, and genetic variation. Several specific IL6 gene polymorphisms correlate with increased serum IL-6 and worse outcomes in several inflammatory disease states including rheumatoid arthritis, multiple sclerosis, and Sjogren's syndrome. We hypothesize that specific IL-6 gene variants, individually or in combinations, contribute to higher levels of serum IL-6 in older adults. In order to test this hypothesis, we will genotype consented WHAS 1 and 2 participants for 5 IL-6 single nucleotide polymorphic variants, determine the association between the IL-6 single and combined gene variants and previously measured baseline visit serum IL-6 in the same cohort, and then determine the relationship between these alleles and skeletal muscle strength and with frailty using the expertise and experience of both the Genetics Research Core and the Biostatistics Research Core. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: POTENTIAL MECHANISMS OF AGE DEPENDENT BONE LOSS Principal Investigator & Institution: Williams, John P.; Associate Professor; Medicine; University of Kentucky 109 Kinkead Hall Lexington, Ky 40506 Timing: Fiscal Year 2002; Project Start 01-MAY-1999; Project End 30-APR-2003 Summary: Osteoporosis is the most common debilitating bone disease affecting 24 million people in the U.S. An estimated 50 percent of women over 45 and 90 percent of women over 75 years of age have osteoporosis, of which approximately half will suffer osteoporotic fractures. The estimated cost of osteoporosis and related fractures is 7-10 billion dollars per year. Bone resorption by osteoclasts is an energy intensive process, requiring ATP hydrolysis by an H+-ATPase to drive proton secretion. Age-dependent changes in bone mass are accompanied by age-dependent changes in other parameters, including glucose intolerance. Osteoclasts are glucose responsive cells that resorb bone in a glucose concentration dependent manner with a Km of 3 mM. The data presented here indicate that osteoclasts have glucose concentration dependent changes in 1) ATP synthesis, 2) phosphate uptake, 3) tyrosine phosphorylation, and 4) phosphatidylinositol 3-kinase activity. In view of the high metabolic demands of bone resorption, I hypothesize that glucose directly alters the activity of osteoclasts by modulating critical signal transduction processes in these cells. The proposed research will define the molecular mechanisms and metabolic requirements responsible for regulating these signal transduction processes. The Specific Aims are to: I: Characterize The Expression Of Glucose Transport Protein (S) In Osteoclasts. A. Determine the effect of bone attachment on GLUT2 expression in osteoclasts. B. Determine whether glucose transporters are translocated to the plasma membrane in response to bone attachment. II: Characterize Metabolic Elements That Govern Osteoclast Activity. A. Determine the rate limiting steps in glucose metabolism by osteoclasts. B. Characterize the glucose dependence of metabolic pathways. III: Identify Ket Signaling Pathways That Regulate Osteoclast Metabolism. A. Determine and characterize the role of glucose in osteoclastic

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phosphatidylinositol-dependent signaling pathways. B. Determine the role of glucose in modulating changes in tyrosine phosphorylation of specific proteins. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PRIMARY PREVENTION PROGRAM -DATA COORDINATING CENTER Principal Investigator & Institution: Fowler, Sarah E.; Research Professor; Statistics; George Washington University 2121 I St Nw Washington, Dc 20052 Timing: Fiscal Year 2002; Project Start 20-AUG-1994; Project End 31-MAY-2003 Summary: (Directly incorporated from the application) The Biostatistics Center of The George Washington University proposes to work in cooperative agreement with the National Institutes of Diabetes and Digestive and Kidney Diseases (NIDDK) to serve as the Data Coordinating Center (DCC) for a proposed multi-center clinical trial of the primary prevention of non-insulin dependent diabetes mellitus (NIDDM). Adiposity and inactivity have been established as critical factors in the etiology of glucose intolerance and are strongly associated with increased risk of glucose intolerance. We propose to determine the safety and efficacy of an intensive lifestyle intervention or prophylactic use of an oral hypoglycemic agent on the incidence of NIDDM among high risk patients (obese, minority, family history of NIDDM, history of gestational diabetes mellitus) in a state of impaired glucose tolerance (IGT). The objective of the one year planning phase is to develop a protocol, operations manual and data collection forms to be implemented in a five year full-scale clinical trial. The trial will require large-scale screening and randomization of 4,000 high risk patients with a diagnosis of IGT over a one year period in 20 clinical centers. Eligible patients will be randomized to "conventional" dietary counseling or one of the comparison groups (intensive lifestyle intervention or an oral hypoglycemic agent). Randomized patients will be followed for a minimum of four years with quarterly follow-up visits. Conversion from a state of IGT to overt NIDDM will be determined by semi-annual 2-hour oral glucose tolerance tests (OGTTs) following a 75 g glucose load confirmed by a central laboratory. Covariates and secondary outcomes include carotid ultrasound imaging, electrocardiograms, serum lipids, albumin excretion rate, adiposity, insulin sensitivity, hemoglobin A1c, and fundus photographs. The specific aims of the DCC are to provide centralized support and biostatistical consultation in the development of the patient management protocols, operations manual, data collection forms and randomization procedures; implementation of a data processing system including data quality assessment; interim analysis of protocol performance, patient safety and treatment efficacy; and final analysis for publication of the results in collaboration with the clinical investigators. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PROGRAM PROJECT IN BIOMEDICAL OUTCOMES OF AGING Principal Investigator & Institution: Minaker, Kenneth L.; Associate Professor; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2002; Project Start 01-JUL-1977; Project End 31-AUG-2007 Summary: GRANT=6423578;P01AG This application seeks renewed support for the Program Project in Biomedical Outcomes of Aging. We hypothesize that age-associated growth hormone declines influence cardiac and peripheral muscle function during congestive heart failure compensation. Finally, we hypothesize that age-related decrements in insulin release and action lead to the glucose intolerance of aging. Building on our preliminary observations we have formulated a common hypothesis

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that trophic factor restoration (employing exogenous agents?GHRH, testosterone, GLP/Exendin) will not only correct the underlying deficiency states but be useful tools to correct the impaired tissue structure or function, and improve the symptoms of functional loss in settings where tissue related illnesses have resulted (CHF, sarcopenia and diabetes mellitus). On a more fundamental level we will explore the mechanisms underlying correction of the "trophic endocrinopathy of aging." Protein synthesis in the heart, peripheral muscle metabolism, growth factors, and hormonal release and action will all be examined before and after hormonal substitution. Common study designs of hormone replacement protocols will be employed to examine structural and functional changes. The shared resources and scientific collaborations int his renewal encompass data management, common analytical procedures (e.g. radioimmunoassays, body composition analysis) and a supply-purchasing system. The Program Project also forms an excellent forum for training of gerontologic investigators, particularly Ph.D. and M.D. trainees entering our institutional programs. The relocation The relocation of the Program Project to the Massachusetts General Hospital following the Principal Investigator's move and the establishment Medicine Unit at the Massachusetts General Hospital opens and extends collaborations. Our new MGH collaborator is Dr. Laurence Katznelson, Endocrine Division. The extensions are Dr. Joel Habner, collaborator of Drs. Elahi and Minaker for many years," and Dr. Ronenn Roubenoff Joseph Kehayias and Ms. Virginia Hughes at the USDA Human Nutrition Research Center on Aging at Tufts University. The significance of each project rests in its contribution to the understanding of physiologic and pathophysiologic mechanisms relevant to the health and the common diseases affecting aging Americans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PROGRAMMING GLUCOCORTICOID SECRETION DURING FETAL LIFE Principal Investigator & Institution: Phillips, David I.; Professor; University of Southampton Highfield Southampton, Timing: Fiscal Year 2002; Project Start 27-SEP-2001; Project End 30-JUN-2004 Summary: (provided by applicant): Epidemiological studies have shown that low birthweight in combination with adult obesity is associated with a marked increase in the prevalence of the metabolic or insulin resistance syndrome (insulin resistance, hypertension, dyslipidaemia and glucose intolerance). This syndrome is in turn associated with an increased risk of both type 2 diabetes and atherosclerotic vascular disease. These observations have led to the hypothesis that adaptations made by the fetus in response to undernutrition give rise to persisting changes in metabolism which lead to insulin resistance and the metabolic syndrome. Although the nature of these changes are not understood, animal studies and preliminary human observations made by the Principal Investigator have led to the hypothesis that in utero resetting of the hypothalamic-pituitary-adrenal (EPA) axis resulting in increased secretion of the adrenal stress hormone, cortisol, is an important change which may initiate the metabolic syndrome. The aim of the studies are to characterize the nature of the abnormality of the HPA axis in adults who were small at birth and the way in which this abnormality interacts with adult obesity to determine the prevalence of the metabolic syndrome or its components. It is expected that the information from these studies will form a first step towards the development of pharmacological strategies aimed at reducing the deleterious effects of low birthweight on adult health. It also has the potential to provide outcome measures in trials of maternal nutrition or other interventions to improve fetal growth and well-being, and by identifying affected

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individuals early in life may allow specific targeting of public health interventions (e.g. obesity reduction). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TOLERANCE

QUANTITATION

OF

FACTORS

REGULATING

GLUCOSE

Principal Investigator & Institution: Bergman, Richard N.; Professor of Physiology and Biophysics; Physiology and Biophysics; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033 Timing: Fiscal Year 2002; Project Start 01-AUG-1981; Project End 31-DEC-2002 Summary: Type 2 diabetes is a complex disease which is caused by a slow progression of decreased glucose tolerance, followed by hyperglycemia. it is of great interest to understand the complex patterns of changes in metabolic function which precede overt hyperglycemia. Three components which can contribute to glucose intolerance are insulin resistance, impaired B-cell function, and reduced glucose effectiveness. The latter process is the ability of glucose itself to enhance carbohydrate disposal and suppress endogenous glucose output. We have obtained data supporting the concept that in normal individuals B-cell function increases to compensate for insulin resistance caused by hereditary or environmental factors. In fact, the mathematical product of insulin sensitivity and insulin secretion is approximately constant. The mechanisms responsible for the hyperbolic relationship between insulin sensitivity and insulin secretion are studied in this proposal. The time course of changes in glucose tolerance and B-cell response will be monitored to elucidate the events which account for the hyperbolic interaction, and to identify the signals in blood which are responsible for this striking relationship. Whether a similar, but less efficient hyperbolic relationship can be maintained when B-cell function is impaired will be examined. Also, we will examine the importance of individual metabolic precesses to glucose effectiveness. The role of glucose production by liver or kidney, as well as glucose uptake by insulin independent and insulin dependent tissues will be assessed. Also examined will be the changes which take place in function of individual tissues when glucose effectiveness changes. These studies should provide an integrated picture of the means by which the intact organism maintains normal maintenance of glucose tolerance when small changes in Bcell function are imposed, and could well provide new insights into the pathogenesis and potential treatment targets for Type 2 diabetes and the prediabetic state. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RAGE AND MECHANISMS OF VASCULAR AND MONOCYTE DYSFUNCTION Principal Investigator & Institution: Schmidt, Ann Marie.; Professor; Physiology/Cellualr Biophysics; Columbia University Health Sciences Po Box 49 New York, Ny 10032 Timing: Fiscal Year 2003; Project Start 01-FEB-1999; Project End 31-JAN-2005 Summary: Sustained endothelial and mononuclear phagocyte dysfunction is critical to the pathogenesis of chronic vascular disorders. Non-enzymatic glycoxidation of proteins and lipids forming Advanced Glycation Endproducts (AGEs) in the vasculature and tissues is accelerated in atherosclerosis, diabetes and renal failure. Interaction of AGES with Receptor for AGE (RAGE) on endothelium and monocytes perturbs cellular properties critical to vascular and tissue homeostatic processes, and causes chronic cellular activation. The central hypothesis of the Program Project is that AGE-RAGE-

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Glucose Intolerance

mediated modulation of endothelial and monocyte functions compromises physiologic effector mechanisms and eventuates in aggressive atherosclerosis, delayed wound repair, and impaired resolution of local inflammation. Employing glucose intolerance as the stimulus for enhanced AGE formation, our pilot studies have shown that antagonism of AGE-RAGE interaction suppresses accelerated atherosclerosis, ameliorates wound healing and diminishes inflammatory consequences of soft tissue infection. Project 1 will exploit our recently developed murine model of accelerated atherosclerosis associated with glucose intolerance to probe the role of RAGE in rapid formation of vascular lesions. Project 2 will extend our concept to a secondary intention wound model in insulin- resistant mice in which AGE-RAGE-mediated cellular dysfunction underlies compromised tissues reparative mechanisms. Project 3 will focus on local inflammation/infection in AGE-rich soft tissues using a model of gingivitis triggered by bacterial infection. The overlapping host response mechanisms triggered by atherogenesis, wound repair and local inflammation, the intimate involvement of endothelium and monocytes, as well as the central role of AGE binding to RAGE, provide the basis for close interactions among the three Projects. By collaborative studies between each of the Projects, the contribution of RAGE will be determined using transgenic mice and mutated RAGE molecules. At the end of this Program Project, we expect to have generated new and important information related to vascular and monocyte dysfunction underlying accelerated atherosclerosis, impaired wound healing and the compromised host response to local inflammation common to disorders characterize by tissue deposition of AGEs. These data should provide insight into a novel target for the development of future therapeutic agents. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REGULATION OF INSULIN GENE EXPRESSION Principal Investigator & Institution: Montminy, Marc R.; Professor; Salk Institute for Biological Studies 10010 N Torrey Pines Rd La Jolla, Ca 920371099 Timing: Fiscal Year 2002; Project Start 15-JUN-1995; Project End 30-JUN-2004 Summary: The homeobox protein pdx1 functions importantly in pancreatic development and in glucose homeostasis. Targeted disruption of the pdx1 gene leads to pancreatic agenesis in pdx1 -/- homozygotes, and pdx +/- heterozygotes develop glucose intolerance as adults. Inactivating mutations in the human pdx1 gene are correlated with maturity onset diabetes of the young, further underscoring the importance of this factor for glycemic control. The long term objective of this proposal is to elucidate the mechanism by which pdx1 stimulates the expression of cellular target genes during development and in response to glucose. Two features of the pdx polypeptide appear to be particularly critical in this regard; a conserved pentapeptide motif that mediates cooperative DNA binding with the ubiquitous homeodomain protein pbx, and an N-terminal trans-activation domain whose activity is induced in response to glucose stimulation. The major hypothesis to be tested is that glucose regulates the transcriptional activity of the pdx/pbx complex by promoting complex formation with the co-activator CBP via a phosphorylation dependent mechanism. This hypothesis will be tested in the following specific aims: 1. We will characterize the mechanism by which the conserved pentapeptide motif in pdx promotes interaction with pbx, and we will evaluate the importance of pdx/pbx complex formation for pancreatic development and glucose homeostasis in transgenic mice. 2. We will characterize a glucose responsive trans-activation domain in pdx-1, and we will identify residues in pdx that are phosphorylated in response to glucose stimulation. 3. We will examine the mechanism by which pdx interacts with the signal dependent co-activator

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CBP, and we will evaluate whether glucose promotes recruitment of CBP to pdx by a phosphorylation dependent mechanism. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ROLE ATHEROSCLEROSIS

OF

FATTY

ACID

BINDING

PROTEINS

IN

Principal Investigator & Institution: Linton, Macrae F.; Professor; Medicine; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2002; Project Start 01-AUG-2000; Project End 31-JUL-2004 Summary: Insulin resistance is a condition associated with a cluster of abnormalities including hypertension, glucose intolerance, hypertriglyceridemia, obesity and premature coronary artery disease. Understanding the molecular basis of the link between insulin resistance and these pathological states has been a difficult task. Elevated plasma levels of free fatty acids are a common hallmark of insulin resistance. Cytoplasmic fatty acid binding proteins (FABP) are small cytoplasmic proteins that bind a variety of fatty acids and are expressed in a tightly regulated, tissue specific manner. Proposed functions of cytoplasmic FABP include trapping and trafficking of fatty acids within cells and cell signaling. Targeted disruption of the aP2 allele has been shown to uncouple obesity and insulin resistance, indicating an important role for aP2 in the insulin resistance. Preliminary studies indicate that aP2 promotes atherosclerosis and macrophage foam cell formation in apoE deficient mice. Mall, a closely related FABP, is also expressed by adipocytes and macrophages and is up-regulated in aP2 deficient mice. The goal of this project is to investigate the impact of aP2 and mall-deficiency on insulin resistance and atherosclerosis. To this end, murine bone marrow transplantation will be used to generate mice chimeric for aP2 and or mall expression by macrophages and or adipocytes allowing the investigation of the relative cell-specific contributions of expression of these genes to atherosclerosis and insulin resistance. Finally, in vitro studies will investigate the role of aP2 and mall in macrophage foam cell formation. By providing new insights into the link between insulin resistance and atherosclerosis, these studies may lead to new therapeutic approaches to diabetes and coronary artery disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ROLE OF GLP-1 IN NORMAL AND ABNORMAL GLUCOSE TOLERANCE Principal Investigator & Institution: D'alessio, David A.; Associate Professor of Medicine; Internal Medicine; University of Cincinnati 2624 Clifton Ave Cincinnati, Oh 45221 Timing: Fiscal Year 2004; Project Start 30-SEP-1999; Project End 31-MAY-2008 Summary: (provided by applicant): Type 2 diabetes constitutes an enormous health burden in the United States, and despite the increasing prevalence of this disease there are still major gaps in understanding the underlying causes. The overall goal of this proposal is to determine the role of the GI hormone glucagon-like peptide 1 (GLP-1) to regulate glucose tolerance in non-diabetic persons and patients with type 2 diabetes. In healthy humans GLP-1 stimulates insulin secretion, and together with other signals arising from the gut during meal absorption, accounts for 30-60% of the insulin secreted. Studies in animals and humans indicate that blocking the action of GLP-1 causes glucose intolerance. In persons with type 2 diabetes, and other forms of abnormal glucose tolerance, the augmentation of insulin secretion by stimuli from the gut, such as

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GLP-1, is severely impaired. The findings from therapeutic trials of GLP-1 and GLP-1agonists support the currently favored model that GLP-1 acts as a hormone. However, recent findings by our group and others have shown that GLP-1 may signal primarily through neural pathways, likely originating in the splanchnic bed. Based on this data we propose that the action of endogenous GLP-1 to stimulate insulin secretion is through a neural reflex originating in the immediate distribution of the portal vein. The specific aims of this project will determine: 1) whether the stimulation of insulin secretion by endogenous GLP-1 in humans is mediated by parasympathetic signaling, and whether this mechanism is abnormal in persons with type 2 diabetes; 2) the mechanisms and pathways of neural activation by which endogenous GLP-1 promotes insulin secretion; 3) the effect of hepatic-portal denervation on glucose tolerance and the response to GLP1. Establishing the role of a neural system by which intestinal GLP-1 acts is important for understanding how post prandial insulin secretion is regulated and why the incretin axis is impaired in diabetic patients. The results of these studies will add to the understanding of the regulation of glucose metabolism by GLP-1 and the incretin axis, and contribute to the development of new strategies to treat type 2 diabetes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TELOMERE INDUCED GENOMIC INSTABILITY IN PREMATURE AGING Principal Investigator & Institution: Chang, Sandy S.; Assistant Professor; Molecular Genetics; University of Texas Md Anderson Can Ctr Cancer Center Houston, Tx 77030 Timing: Fiscal Year 2004; Project Start 01-JUL-2004; Project End 31-MAY-2007 Summary: (provided by applicant): Genetic studies of human progeric syndromes have furthered our understanding of the molecular mechanisms of the aging process. Mutations in Wrn causes Wemer Syndrome (WS), a disease characterized by premature aging, elevated genomic instability and cancer. WS fibroblasts prematurely senescence due to telomere shortening, suggesting the possibility that telomere dysfunction collaborates with Wrn loss to generate WS. Telomeres function to prevent chromosomal ends from being recognized as double-strand DNA breaks and confer genome stability. It has been postulated that telomere shortening serves as a molecular clock that eventually signals replicative senescence. WS cells senescence while still possessing long telomeres, suggesting that they may be hypersensitive to telomere shortening. This hypothesis is supported by the observation that the senescence phenotype observed in WS cells can be rescued by overexpression of telomerase, suggesting that one consequence of the WS defect is the acceleration of normal telomere-based senescence. Mice lacking WRN do not display obvious aging phenotypes, and I hypothesize that manifestation of the WS phenotype requires the presence of critically short telomeres. Mouse telomeres are normally too long for the required telomere attrition to take place during the aging process. To test experimentally the hypothesis that manifestation of the WS phenotype in WRN-/- mice requires critical telomere shortening, telomere lengths were shortened genetically via successive intercrossings of WRN-/- mTERC-/- mice. Compound mutant mice with short dysfunctional telomeres exhibited early onset of aging phenotypes, including alopecia, cataract formation and glucose intolerance and died prematurely. These exciting results suggest that our mouse model recapitulates features of WS observed in human patients. Our immediate goal is to characterize additional aging phenotypes in these mice and to correlate the onset of premature aging with genomic instability induced by telomere dysfunction. We are also probing for molecular mechanisms that may be responsible for the observed aging phenotypes in

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our mouse model. These studies should illuminate the roles of Wrn and dysfunctional telomeres during human aging. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: UNIV OF NORTH CAROLINA CLINICAL NUTRITION RESEARCH UNIT Principal Investigator & Institution: Zeisel, Steven H.; Professor and Chair; Nutrition; University of North Carolina Chapel Hill Aob 104 Airport Drive Cb#1350 Chapel Hill, Nc 27599 Timing: Fiscal Year 2002; Project Start 30-SEP-1999; Project End 29-SEP-2004 Summary: We propose a CNRU that is specifically designed to enhance the translation of basic science information and technology into population-based and clinical nutrition research, and also to facilitate the transfer of ideas and information in the opposite direction. These population-based studies are the major approach for preention information in the opposite direction. These population-based studies are the major approach for prevention research, which requires the study of many subjects to detect the smaller magnitude changes in outcome measures research, which requires the study of many subjects to detect the smaller magnitude changes in outcome measures that typify nutrition versus drug studies. A major reason to locate a CNRU at UNC-CH is the strength and interdisciplinary breadth of our research programs in nutrition. Fifty-five active investigators conduct research that spans areas of basic, clinical and applied science relevant to human nutrition, including clinical nutrition, metabolic biochemistry, molecular biology, gastroenterology, hepatology, pharmacology, health behavior, nutrition epidemiology, physiology, oncology, and endocrinology. Excellent graduate students and postdoctoral fellows are working with CNRU investigators, and CNRU faculty are the awardees for four T32 training grants from the NIDDK, NHLBI, NIEHS and NCI. Our research base generates more than $20 million in annual NIH-funded (or equivalent), nutrition-related research support. CNRU faculty are appointed in many departments including nutrition, medicine, pharmacology, pediatrics, biostatistics, epidemiology, cell and molecular physiology, nutrition, medicine, pharmacology, pediatrics, biostatistics, epidemiology, cell and molecular physiology, nutrition, medicine, pharmacology, pediatrics, biostatistics, epidemiology, cell and molecular physiology, pathology, and environmental. Steven Zeisel, MD serves as CNRU director, and Rosalind Coleman, MD as associate director. An internal governance committee (consisting of the director, associate director, three core directors, and two representatives of the CNRU faculty) will maintain the quality, objectivity, and continuity of directors, and two representatives of thee CNRU faculty) will maintain the quality, objectivity and continuity of directors, and two representatives of the CNRU faculty) will maintain the quality, objectivity and continuity of policies that govern the CNRU. An external advisory committee will be established. The Administrative Core will be responsible for management of the CNRU and will provide biostatistical support, grant pre-review services, facilitation of access to research populations, computer support, an enrichment program, a medical student education program (including leadership of a national curriculum initiative), a pilot and feasibility grant program, a education program (including leadership of a national curriculum initiative), a pilot and feasibility grant program, a education program (including leadership of a national curriculum initiative, a pilot and feasibility grant program, a education program (including leadership of a national curriculum initiative), a pilot and feasibility grant program, a young investigator award, community outreach and public education. Several of these activities will be conducted in collaboration with the UNC-CH General

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Glucose Intolerance

Clinical Research Center. The proposed Translational Core for Population Studies, led by Lenore Kohlmeier, Ph.D., is designed to facilitate the translation of new findings and technology into outgoing research projects and to stimulate the incorporation of state of the art methodology in population based human nutrition studies. The core services will be in five areas: incorporation of biomarkers of dietary intake in ongoing studies, technical support in the preparation of multi-mediate based dietary assessment, statistical support in the design and analyses of epidemiology studies, support in the preparation of an access to nutritional data on foods and nutrient supplements for estimation of intakes and support with the complex statistical nutritional data on foods and nutrient supplements for estimation of intakes and support5 with the complex statistical nutritional data on foods and nutrition support in the preparation of multi media based dietary assessment statistical in the design and analyses of epidemiological studies, support in the preparation in the preparation of and access to nutritional data on foods and nutrient supplements for estimation of intakes and support with the complex statistical analyses needed to insure the appropriate supplements for estimation of intakes and support with the complex statistical analyses needed to insure the appropriate conclusions from population studies on diet and health. The purpose of analyses needed to insure the appropriate conclusions from population studies on diet and health. The purpose of the Molecular Biology and Nutritional Biochemistry Core, directed by Melinda Beck, Ph.D., is to provide a state-of-the-art facility for nutrition research investigators. The core will serve as an educational and training resource for the development and application of molecular biology techniques and biomarkers for nutritional research. It will provide a number of specialized techniques requested by CNRU investigators. In addition, the Core will provide consultation and assistance to investigators who may just be beginning to use molecular techniques and biomarkers in their research. The Nutrition Intervention Core, directed by Marci Campbell, Ph.D., will provide expertise and state-of-the-art resources and techniques for developing and evaluation nutritional interventions aimed at promoting health and preventing disease and populations at risk. CNRU. Investigators will have access to intervention development and tracking tools, and will receive help and consultation on their application to each project. Five junior investigators propose P/F projects on Selenium and arsenic toxicity. Gene targeted animal models for CVD, Church-based nutrition intervention in African Americans, Epidemiology of glucose intolerance during pregnancy, and Vitamin D therapy for bone disease in cystic fibrosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: VASCULAR AND MONOCYTE DYSFUNCTION IN WOUND REPAIR Principal Investigator & Institution: Andres, Giuseppe; Columbia University Health Sciences Po Box 49 New York, Ny 10032 Timing: Fiscal Year 2002 Summary: Tissue and vascular deposition of Advanced Glycation Endproducts (AGEs), irreversible products of glycoxidation of proteins and lipids, occurs during normal aging and is accelerated by concomitant glucose intolerance or renal failure. Thus, normal host reparative mechanisms, such as those set in motion by wounding must proceed in an environment rich in AGEs. Cells critical to orchestration of wound healing, especially endothelial cells (ECs) and mononuclear phagocytes (MPs), express Receptor for AGE (RAGE), a principal cell surface binding site for AGEs. Consequent to engagement bu AGEs, RAGE brings about changes in cellular functions central to tissue reparative mechanisms triggered during the inflammatory, proliferative and remodeling phases of healing. Pilot studies using a secondary intention would model in glucose

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intolerant mice, the latter to accelerate AGE deposition, have shown delayed healing compared with control animals. Wound closure in this model is enhanced, almost to levels in euglycemic controls, by local or systemic administration of a truncated hypothesis that AGE binding to RAGE on critical cellular targets, especially ECs and MPs, modulates their participation in reparative processes by promoting sustained activation, leading to a chronic, destructive inflammatory response. Our specific aims are: (1) to analyze, in the secondary intention wound model, the effect of sRAGE on differences in the reparative response in glucose-intolerant amd euglycemic mice, by monitoring activation of ECs, influx and activation of MPs, production of proinflammatory cytokines, growth factors, and the balance of collagen synthesis/degradation; (2) to produce new transgenic murine models for evaluating the contribution of AGE-RAGE interaction to wound healing by cross-breeding transgenic (Tg) mice with targeted overexpression of full- length RAGE or a dominant negative form of the receptor in MPs or ECs with glucose intolerant mice, and to determine the effect on the reparative response: and (3) to identify determinants on RAGE mediating interaction with AGEs. Project 2 will work closely with Projects 1&3 and will obtain technical assistance from the Cores. Collaborative interactions will include: development and characterization of Tg RAGE mice (Projects 1&3 and Core C), collagen/collagenase evaluation (Project 2), transcriptional analysis of RAGE expression (Project 1), and pathologic study of tissues (Core B). 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 “glucose intolerance” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for glucose intolerance in the PubMed Central database: •

Inhibition of adipogenesis and development of glucose intolerance by soluble preadipocyte factor --1 (Pref-1). by Lee K, Villena JA, Moon YS, Kim KH, Lee S, Kang C, Sul HS.; 2003 Feb 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151920

•

Mechanisms of Epinephrine-induced Glucose Intolerance in Normal Humans ROLE OF THE SPLANCHNIC BED. by Sacca L, Vigorito C, Cicala M, Ungaro B, Sherwin RS.; 1982 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=370977

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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Role of parathyroid hormone in the glucose intolerance of chronic renal failure. by Akmal M, Massry SG, Goldstein DA, Fanti P, Weisz A, DeFronzo RA.; 1985 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=423657

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 glucose intolerance, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “glucose intolerance” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for glucose intolerance (hyperlinks lead to article summaries): •

A comparison of left ventricular abnormalities associated with glucose intolerance in African Caribbeans and Europeans in the UK. Author(s): Chaturvedi N, McKeigue PM, Marmot MG, Nihoyannopoulos P. Source: Heart (British Cardiac Society). 2001 June; 85(6): 643-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11359744

•

A cross-sectional study of dietary patterns with glucose intolerance and other features of the metabolic syndrome. Author(s): Williams DE, Prevost AT, Whichelow MJ, Cox BD, Day NE, Wareham NJ. Source: The British Journal of Nutrition. 2000 March; 83(3): 257-66. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10884714

•

A low socio-economic status is an additional risk factor for glucose intolerance in high risk Hong Kong Chinese. Author(s): Ko GT, Chan JC, Yeung VT, Chow CC, Tsang LW, Cockram CS. Source: European Journal of Epidemiology. 2001; 17(3): 289-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11680550

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 new familial syndrome characterized by pigmentary retinopathy, hypogonadism, mental retardation, nerve deafness and glucose intolerance. Author(s): Edwards JA, Sethi PK, Scoma AJ, Bannerman RM, Frohman LA. Source: The American Journal of Medicine. 1976 January; 60(1): 23-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1251844

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A preliminary assessment of acculturation and its relationship to body size and glucose intolerance among Blacks in the US Virgin Islands. Author(s): Tull ES, Ambrose JJ, Chambers E. Source: Ethn Dis. 2003 Winter; 13(1): 15-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12723007

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A quantitative trait locus that accounts for glucose intolerance maps to chromosome 8 in hereditary obese KK-A(y) mice. Author(s): Suto J, Sekikawa K. Source: International Journal of Obesity and Related Metabolic Disorders : Journal of the International Association for the Study of Obesity. 2002 November; 26(11): 1517-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12439655

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Abdominal obesity and glucose intolerance in middle-aged women in the United Arab Emirates. Author(s): al Tajer SS, Hossain MM, Pugh RN. Source: Journal of Public Health Medicine. 1995 September; 17(3): 362-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8527192

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Abnormal cortisol metabolism and tissue sensitivity to cortisol in patients with glucose intolerance. Author(s): Andrews RC, Herlihy O, Livingstone DE, Andrew R, Walker BR. Source: The Journal of Clinical Endocrinology and Metabolism. 2002 December; 87(12): 5587-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12466357

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Absence of capillary microangiopathy in oral contraceptive users with glucose intolerance. Author(s): Goldzieher JW, Villegas-Castrejon H, Cervantes A, Maqueo M, Siperstein MD. Source: Obstetrics and Gynecology. 1978 January; 51(1): 89-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=619342

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Age and glucose intolerance: effect of fitness and fatness. Author(s): Reaven G. Source: Diabetes Care. 2003 February; 26(2): 539-40. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12547897

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•

Age, body mass index and 2-hour plasma glucose are the major determinants of blood pressure in Chinese women newly diagnosed to have glucose intolerance. Author(s): Ko GT, Chan JC, Cockram CS. Source: International Journal of Cardiology. 1999 April 30; 69(1): 33-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10362370

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Age-related alteration of pancreatic beta-cell function. Increased proinsulin and proinsulin-to-insulin molar ratio in elderly, but not in obese, subjects without glucose intolerance. Author(s): Shimizu M, Kawazu S, Tomono S, Ohno T, Utsugi T, Kato N, Ishi C, Ito Y, Murata K. Source: Diabetes Care. 1996 January; 19(1): 8-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8720525

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Age-related glucose intolerance in hyperthyroid patients. Author(s): Ikejiri K, Yamada T, Ogura H, Matsumoto, Kobe. Source: Diabetes. 1978 May; 27(5): 543-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=648744

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Aging exaggerates glucose intolerance following injury. Author(s): Watters JM, Moulton SB, Clancey SM, Blakslee JM, Monaghan R. Source: The Journal of Trauma. 1994 November; 37(5): 786-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7966476

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Amniotic fluid insulin at 14-20 weeks' gestation: association with later maternal glucose intolerance and birth macrosomia. Author(s): Carpenter MW, Canick JA, Hogan JW, Shellum C, Somers M, Star JA. Source: Diabetes Care. 2001 July; 24(7): 1259-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11423512

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An assessment of glucose intolerance in acromegaly and its response to medical treatment. Author(s): Wass JA, Cudworth AG, Bottazzo GF, Woodrow JC, Besser GM. Source: Clinical Endocrinology. 1980 January; 12(1): 53-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7379314

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Antihypertensives and glucose intolerance. Author(s): Ibrahim B. Source: The American Journal of Cardiology. 1993 February 15; 71(5): 493-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8430656

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Aortic pulse-wave velocity and its relationship to mortality in diabetes and glucose intolerance: an integrated index of vascular function? Author(s): Cruickshank K, Riste L, Anderson SG, Wright JS, Dunn G, Gosling RG. Source: Circulation. 2002 October 15; 106(16): 2085-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12379578

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Are African American patients at a higher risk for olanzapine-induced glucose intolerance? Author(s): Ananth J, Gunatilake S, Aquino S, Bach V, Costa J. Source: Psychopharmacology. 2001 September; 157(3): 324-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11605090

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Are the increased Lp(a) levels in hemodialysis patients related to glucose intolerance and hemodialysis duration? Author(s): Elisaf M, Siamopoulos KC. Source: Nephron. 1996; 74(3): 623-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8938695

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Assessment of glucose intolerance and insulin sensitivity in polycystic ovary syndrome. Author(s): Yildiz BO, Gedik O. Source: Reproductive Biomedicine Online. 2004 June; 8(6): 649-56. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15169580

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Association between a low adipose tissue content of polyunsaturated fatty acids and both glucose intolerance and hypertriglyceridemia in apparently healthy men. Author(s): Carlson LA, Walldius G. Source: Acta Med Scand. 1975 April; 197(4): 295-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1136857

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Association between polycystic ovary syndrome and glucose intolerance during pregnancy. Author(s): Lesser KB, Garcia FA. Source: The Journal of Maternal-Fetal Medicine. 1997 September-October; 6(5): 303-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9360193

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Association between the SstI polymorphism of the apolipoprotein C-III gene, glucose intolerance and cardiovascular risk in renal transplant recipients. Author(s): Rodrigo E, Gonzalez-Lamuno D, Ruiz JC, Fresnedo GF, Isla D, Cotorruelo JG, Zubimendi JA, de Francisco AL, Garcia-Fuentes M, Arias M. Source: Transplantation Proceedings. 2002 February; 34(1): 379. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11959336

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Glucose Intolerance

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Association of HELLP syndrome with autoimmune antibodies and glucose intolerance. Author(s): Weitgasser R, Spitzer D, Kartnig I, Zajc M, Staudach A, Sandhofer F. Source: Diabetes Care. 2000 June; 23(6): 786-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10840997

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Association of high serum ferritin concentration with glucose intolerance and insulin resistance in healthy people. Author(s): Haap M, Fritsche A, Mensing HJ, Haring HU, Stumvoll M. Source: Annals of Internal Medicine. 2003 November 18; 139(10): 869-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14623634

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Association of HLA antigens with glucose intolerance following renal transplantation. Author(s): d'Apice AJ, Mathews JD, Tait BD, Kincaid-Smith P. Source: Tissue Antigens. 1978 May; 11(5): 423-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=358493

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Association of the Trp64Arg mutation of the beta3-adrenergic receptor with fatty liver and mild glucose intolerance in Japanese subjects. Author(s): Shima Y, Tsukada T, Nakanishi K, Ohta H. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 1998 June 22; 274(2): 167-76. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9694585

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Audit of maternal and fetal outcomes in women treated for glucose intolerance during pregnancy. Author(s): McIntyre HD, Begg LM, Parry AF, Oats J. Source: The Australian & New Zealand Journal of Obstetrics & Gynaecology. 2002 February; 42(1): 23-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11926637

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Autoantibodies to pancreatic hsp60 precede the development of glucose intolerance in patients with cystic fibrosis. Author(s): Jensen P, Johansen HK, Carmi P, Hoiby N, Cohen IR. Source: Journal of Autoimmunity. 2001 September; 17(2): 165-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11591125

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Beta 2-sympathomimetic activation as a cause of posthypoglycemic glucose intolerance. Author(s): Petersen KG, Kerp L. Source: Hormone and Metabolic Research. Hormon- Und Stoffwechselforschung. Hormones Et Metabolisme. 1988 March; 20(3): 171-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3290078

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Beta-cell dysfunction independent of obesity and glucose intolerance in the polycystic ovary syndrome. Author(s): Dunaif A, Finegood DT. Source: The Journal of Clinical Endocrinology and Metabolism. 1996 March; 81(3): 942-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8772555

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Birthweight in women with potential gestational diabetes mellitus--an effect of obesity rather than glucose intolerance? Author(s): Lauszus FF, Paludan J, Klebe JG. Source: Acta Obstetricia Et Gynecologica Scandinavica. 1999 July; 78(6): 520-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10376862

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Body mass index, waist circumference, waist-hip ratio, and glucose intolerance in Chinese and Europid adults in Newcastle, UK. Author(s): Unwin N, Harland J, White M, Bhopal R, Winocour P, Stephenson P, Watson W, Turner C, Alberti KG. Source: Journal of Epidemiology and Community Health. 1997 April; 51(2): 160-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9196645

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Can glucose intolerance and/or diabetes be predicted in patients treated with rhGH? Author(s): Hokken-Koelega AC. Source: Br J Clin Pract Suppl. 1996 August; 85: 56-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8995034

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Cardiovascular risk factors in African-Americans with varying degrees of glucose intolerance. Author(s): Osei K, Gaillard T, Schuster DP. Source: Diabetes Care. 1999 September; 22(9): 1588-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10480533

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Characteristics of glucose intolerance in alcoholics with liver cirrhosis during abstinence especially with reference to catecholamines. Author(s): Ihori M, Harada T, Omori R, Ueda H. Source: Gastroenterol Jpn. 1978; 13(5): 366-73. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=729998

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Chronic renal failure and secondary hyperparathyroidism are responsible for glucose intolerance and impaired insulin secretion of aging. Author(s): Massry SG, Fadda GZ. Source: J Endocrinol Invest. 1992; 15(9 Suppl 6): 73-7. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1300343

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Cigarette smoking, oral moist snuff use and glucose intolerance. Author(s): Persson PG, Carlsson S, Svanstrom L, Ostenson CG, Efendic S, Grill V. Source: Journal of Internal Medicine. 2000 August; 248(2): 103-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10947888

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Circulating concentrations of insulin-like growth factor-I and development of glucose intolerance: a prospective observational study. Author(s): Sandhu MS, Heald AH, Gibson JM, Cruickshank JK, Dunger DB, Wareham NJ. Source: Lancet. 2002 May 18; 359(9319): 1740-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12049864

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Classification of glucose intolerance in the aged based on hemoglobin A1. Author(s): Nakao J, Orimo H, Ito H. Source: The Tohoku Journal of Experimental Medicine. 1980 November; 132(3): 305-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7466810

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Clinical characteristics of transient glucose intolerance during acute diarrhoea. Author(s): Ozmert E, Yurdakok K, Aslan D, Yalcin SS, Yardim M. Source: Acta Paediatrica (Oslo, Norway : 1992). 1999 October; 88(10): 1071-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10565451

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Clinical lipoatrophy in HIV-1 patients on HAART is not associated with increased abdominal girth, hyperlipidaemia or glucose intolerance. Author(s): Worm D, Kirk O, Andersen O, Vinten J, Gerstoft J, Katzenstein TL, Nielsen H, Pedersen C. Source: Hiv Medicine. 2002 October; 3(4): 239-46. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12444941

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Clinical significance of compound quinestrol-caused glucose intolerance. Author(s): Zhu XX, He DH, Wang ZG, Chen JH, He WT, Qiu CL, Zhong XL. Source: Chinese Medical Journal. 1980 September; 93(9): 651-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6775900

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Community screening for glucose intolerance in middle-aged Icelandic men. Deterioration to diabetes over a period of 71/2 years. Author(s): Sigurdsson G, Gottskalksson G, Thorsteinsson T, Davidsson D, Olafsson O, Samuelsson S, Sigfusson N. Source: Acta Med Scand. 1981; 210(1-2): 21-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7293824

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Comparability of blood glucose concentrations measured in different sample systems for detecting glucose intolerance. Author(s): Haeckel R, Brinck U, Colic D, Janka HU, Puntmann I, Schneider J, Viebrock C. Source: Clinical Chemistry. 2002 June; 48(6 Pt 1): 936-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12029012

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Comparing fasting plasma glucose against two-hour post-load glucose concentrations for the diagnosis of diabetes mellitus and glucose intolerance in Singaporean hospital patients. Author(s): Chen YT, Mukherjee JJ, Lee CH, Au VS, Tavintharan S. Source: Ann Acad Med Singapore. 2002 March; 31(2): 189-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11957556

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Comparison of ADA and WHO criteria for diagnosis of diabetes and glucose intolerance. Author(s): Larsson H, Berglund G, Lindgarde F, Ahren B. Source: Diabetologia. 1998 September; 41(9): 1124-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9754834

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Comparison of home glucose monitoring with the oral glucose tolerance test to detect gestational glucose intolerance. Author(s): Peterson KA, Peterson AM, Corbett V, Tongen S, Guzman M, Mazze R. Source: The Journal of Family Practice. 1994 December; 39(6): 558-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7798859

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Concordance between fasting and 2-h post-glucose challenge criteria for the diagnosis of diabetes mellitus and glucose intolerance in high risk individuals. Author(s): Drzewoski J, Czupryniak L. Source: Diabetic Medicine : a Journal of the British Diabetic Association. 2001 January; 18(1): 29-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11168338

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Cortisol metabolism and glucose intolerance. Author(s): Kerstens MN, Dullaart RP. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 June; 88(6): 2951; Author Reply 2951-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12788912

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Cross-sectional but not longitudinal associations between non-esterified fatty acid levels and glucose intolerance and other features of the metabolic syndrome. Author(s): Byrne CD, Maison P, Halsall D, Martensz N, Hales CN, Wareham NJ. Source: Diabetic Medicine : a Journal of the British Diabetic Association. 1999 December; 16(12): 1007-15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10656229

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Decline in incidence of epidemic glucose intolerance in Nauruans: implications for the "thrifty genotype". Author(s): Dowse GK, Zimmet PZ, Finch CF, Collins VR. Source: American Journal of Epidemiology. 1991 June 1; 133(11): 1093-104. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2035513

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Decreased insulin-mediated but not non-insulin-dependent glucose disposal rates in glucose intolerance and type II diabetes in African (Ghanaian) immigrants. Author(s): Osei K, Schuster DP. Source: The American Journal of the Medical Sciences. 1996 March; 311(3): 113-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8615385

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Delineating the relationship between stress, depressive symptoms, and glucose intolerance. Author(s): Grandinetti A, Kaholokula JK, Chang HK. Source: Diabetes Care. 2000 September; 23(9): 1443-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10977057

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Detecting glucose intolerance after gestational diabetes: inadequacy of fasting glucose alone and risk associated with gestational diabetes and second trimester waist-hip ratio. Author(s): Jacob Reichelt AA, Ferraz TM, Rocha Oppermann ML, Costa e Forti A, Duncan BB, Fleck Pessoa E, Schmidt MI. Source: Diabetologia. 2002 March; 45(3): 455-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11914756

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Detection of glucose intolerance in pregnancy. Author(s): Mazze RS. Source: Int J Clin Pharmacol Ther Toxicol. 1993 September; 31(9): 440-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8225693

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Detection of glucose intolerance in pregnancy. Author(s): Helton DG, Martin RW, Martin JN Jr, Meeks GR, Morrison JC. Source: Journal of Perinatology : Official Journal of the California Perinatal Association. 1989 September; 9(3): 259-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2809777

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Diabetes and glucose intolerance as risk factors for stroke. Author(s): Tuomilehto J, Rastenyte D. Source: Journal of Cardiovascular Risk. 1999 August; 6(4): 241-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10501276

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Diabetes Screening in Canada (DIASCAN) Study: prevalence of undiagnosed diabetes and glucose intolerance in family physician offices. Author(s): Leiter LA, Barr A, Belanger A, Lubin S, Ross SA, Tildesley HD, Fontaine N; Diabetes Screening in Canada (DIASCAN) Study. Source: Diabetes Care. 2001 June; 24(6): 1038-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11375367

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Diabetic glomerulosclerosis without glucose intolerance. Author(s): Nash DA Jr, Rogers PW, Langlinais PC, Bunn SM Jr. Source: The American Journal of Medicine. 1975 August; 59(2): 191-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1155478

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Diabetic ketoacidosis in an HIV patient: a new mechanism of HIV protease inhibitorinduced glucose intolerance. Author(s): Kan VL, Nylen ES. Source: Aids (London, England). 1999 October 1; 13(14): 1987-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10513665

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Diagnostic criteria for diabetes mellitus and other categories of glucose intolerance: 1997 criteria by the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus (ADA), 1998 WHO consultation criteria, and 1985 WHO criteria. World Health Organization. Author(s): Puavilai G, Chanprasertyotin S, Sriphrapradaeng A. Source: Diabetes Research and Clinical Practice. 1999 April; 44(1): 21-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10414936

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Diagnostic criteria of glucose intolerance and mortality. Author(s): Qiao Q, Tuomilehto J. Source: Minerva Med. 2001 April; 92(2): 113-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11323573

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Diagnostic strategies to detect glucose intolerance in a multiethnic population. Author(s): Anand SS, Razak F, Vuksan V, Gerstein HC, Malmberg K, Yi Q, Teo KK, Yusuf S. Source: Diabetes Care. 2003 February; 26(2): 290-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12547851

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Dietary change and obesity associated with glucose intolerance in Alaska Natives. Author(s): Murphy NJ, Schraer CD, Thiele MC, Boyko EJ, Bulkow LR, Doty BJ, Lanier AP. Source: Journal of the American Dietetic Association. 1995 June; 95(6): 676-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7759744

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Dietary patterns and glucose intolerance among aural Indian populations. Author(s): Rao PV. Source: J Indian Med Assoc. 2002 March; 100(3): 137-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12408269

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Dietary patterns in a high-risk population for glucose intolerance. Japanese-Brazilian Diabetes Study Group. Author(s): Costa MB, Ferreira SR, Franco LJ, Gimeno SG, Iunes M. Source: J Epidemiol. 2000 March; 10(2): 111-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10778035

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Digoxin-like immunoreactivity may contribute to hyperinsulinemia-associated hypertension in patients with glucose intolerance. Author(s): Takahashi H, Matsusawa M, Nishimura M, Nakanishi T, Yoshimura M. Source: Journal of Cardiovascular Pharmacology. 1993; 22 Suppl 2: S22-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7508019

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Does maternal glucose intolerance affect the length of gestation in singleton pregnancies? Author(s): Lao TT, Ho LF. Source: Journal of the Society for Gynecologic Investigation. 2003 September; 10(6): 36671. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12969780

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Dysregulation of the insulin/IGF binding protein-1 axis in transgenic mice is associated with hyperinsulinemia and glucose intolerance. Author(s): Crossey PA, Jones JS, Miell JP. Source: Diabetes. 2000 March; 49(3): 457-65. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10868969

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Effect of 1,25 (OH)2D3 treatment on glucose intolerance in uraemia. Author(s): Turk S, Yeksan M, Tamer N, Gurbilek M, Erdogan Y, Erkul I. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 1992; 7(12): 1207-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1337161

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Effect of acarbose on glucose intolerance in patients with non-insulin-dependent diabetes mellitus. Author(s): Noda K, Umeda F, Nawata H. Source: Diabetes Research and Clinical Practice. 1997 August; 37(2): 129-36. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9279483

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Effect of habitual physical activity on age-related glucose intolerance. Author(s): Wang JT, Ho LT, Tang KT, Wang LM, Chen YD, Reaven GM. Source: Journal of the American Geriatrics Society. 1989 March; 37(3): 203-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2645353

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Effect of macronutrient intake on the development of glucose intolerance during pregnancy. Author(s): Saldana TM, Siega-Riz AM, Adair LS. Source: The American Journal of Clinical Nutrition. 2004 March; 79(3): 479-86. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14985225

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Effect of overweight and obesity on glucose intolerance and dyslipidemia in Saudi Arabia, epidemiological study. Author(s): Rahman Al-Nuaim A. Source: Diabetes Research and Clinical Practice. 1997 June; 36(3): 181-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9237785

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Effect of past and concurrent body mass index on prevalence of glucose intolerance and type 2 (non-insulin-dependent) diabetes and on insulin response. The Israel study of glucose intolerance, obesity and hypertension. Author(s): Modan M, Karasik A, Halkin H, Fuchs Z, Lusky A, Shitrit A, Modan B. Source: Diabetologia. 1986 February; 29(2): 82-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3516770

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Effect of physical activity on age-related glucose intolerance. Author(s): Laws A, Reaven GM. Source: Clinics in Geriatric Medicine. 1990 November; 6(4): 849-63. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2224751

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Effects of heparin-induced non-esterified free fatty acid on minimal model-derived insulin sensitivity in individuals with varying degrees of glucose intolerance. Author(s): Osei K, Schuster DP. Source: Diabetic Medicine : a Journal of the British Diabetic Association. 1995 October; 12(10): 911-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8846683

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Effects of new criteria for type 2 diabetes on the rate of postpartum glucose intolerance in women with gestational diabetes. Author(s): Conway DL, Langer O. Source: American Journal of Obstetrics and Gynecology. 1999 September; 181(3): 610-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10486471

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Effects of obesity, hyperinsulinemia, and glucose intolerance on insulin action in adipose tissue of sixty-year-old men. Author(s): Bolinder J, Lithell H, Skarfors E, Arner P. Source: Diabetes. 1986 March; 35(3): 282-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3512339

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Effects of perindopril on glucose and lipid metabolism in patients with mild-tomoderate essential hypertension and glucose intolerance. Author(s): Uchida K, Azukizawa S, Kigoshi T, Nakano S, Kaneko M, Morimoto S, Matsui A. Source: Clinical Therapeutics. 1994 May-June; 16(3): 466-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7923313

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Effects of physical training and diet therapy on carbohydrate metabolism in patients with glucose intolerance and non-insulin-dependent diabetes mellitus. Author(s): Bogardus C, Ravussin E, Robbins DC, Wolfe RR, Horton ES, Sims EA. Source: Diabetes. 1984 April; 33(4): 311-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6368289

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Effects of very low calorie diet (VLCD) on body weight, blood glucose and serum lipid metabolism in severe obesity with glucose intolerance. Author(s): Inoue S, Okamura A, Okamoto M, Tanaka K, Sugimasa T, Takamura Y. Source: Int J Obes. 1989; 13 Suppl 2: 183-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2613422

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Epidemiology of glucose intolerance and associated factors in Uzbekistan: a survey in Sirdaria province. Author(s): King H, Djumaeva S, Abdullaev B, Gacic Dobo M. Source: Diabetes Research and Clinical Practice. 2002 January; 55(1): 19-27. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11755475

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Epidemiology of glucose intolerance and gestational diabetes in women of childbearing age. Author(s): King H. Source: Diabetes Care. 1998 August; 21 Suppl 2: B9-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9704221

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Estimate of prevalence of glucose intolerance in chronic liver disease. Degree of agreement among some diagnostic criteria. Author(s): Buzzelli G, Chiarantini E, Cotrozzi G, Relli P, Matassi L, Romanelli RG, Gentilini P. Source: Liver. 1988 December; 8(6): 354-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3265171

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Estimated prevalence of undiagnosed glucose intolerance from hyperandrogenic anovulation among women requesting electrolysis. Author(s): Dumesic DA, Herrmann RR, O'Brien AM. Source: Int J Fertil Womens Med. 1997 July-August; 42(4): 255-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9309459

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Evaluation of glucose intolerance in pregnancy using biochemical markers of fetal hyperinsulinemia. Author(s): Roach VJ, Fung H, Cockram CS, Lau TK, Rogers MS. Source: Gynecologic and Obstetric Investigation. 1998; 45(3): 174-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9565141

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Evaluation of insulin release and relative peripheral resistance with use of the oral glucose tolerance test: a study in subjects with normoglycaemia, glucose intolerance and non-insulin-dependent diabetes mellitus. Author(s): Cederholm J, Wibell L. Source: Scandinavian Journal of Clinical and Laboratory Investigation. 1985 December; 45(8): 741-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3909372

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Exercise training delineates the importance of B-cell dysfunction to the glucose intolerance of human aging. Author(s): Kahn SE, Larson VG, Schwartz RS, Beard JC, Cain KC, Fellingham GW, Stratton JR, Cerqueira MD, Abrass IB. Source: The Journal of Clinical Endocrinology and Metabolism. 1992 June; 74(6): 1336-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1592879

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Factors influencing the development of glucose intolerance in Cushing syndrome. Author(s): Scand J Gastroenterol. 1995 Dec;30(12):1228 Source: Acta Medica Austriaca. 1995; 22(5): 110-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9053980

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Familial glucose-galactose malabsorption: remission of glucose intolerance. Author(s): Elsas LJ 2nd, Lambe DW Jr. Source: The Journal of Pediatrics. 1973 August; 83(2): 226-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4717580

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Fasting blood sugar level: a determinant for in-hospital outcome in patients with first myocardial infarction and without glucose intolerance. Author(s): Mak KH, Mah PK, Tey BH, Sin FL, Chia G. Source: Ann Acad Med Singapore. 1993 May; 22(3): 291-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8373106

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Fatty acid composition of serum cholesterol esters in different degrees of glucose intolerance: a population-based study. Author(s): Salomaa V, Ahola I, Tuomilehto J, Aro A, Pietinen P, Korhonen HJ, Penttila I. Source: Metabolism: Clinical and Experimental. 1990 December; 39(12): 1285-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2246969

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Fetal loss and maternal glucose intolerance. A retrospective study. Author(s): Sutherland HW, Fisher PM. Source: Padiatr Padol. 1982; 17(2): 279-86. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7099681

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First-phase insulin response to glucose in nonobese or obese subjects with glucose intolerance: analysis by C-peptide secretion rate. Author(s): Kanatsuka A, Makino H, Sakurada M, Hashimoto N, Iwaoka H, Yamaguchi T, Taira M, Yoshida S, Yoshida A. Source: Metabolism: Clinical and Experimental. 1988 September; 37(9): 878-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3047522

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Frequency of occurrence and interpretation of glucose intolerance in patients with Addison's disease. Author(s): Vandeput Y, Buysschaert M, Irvine WJ, Crabbe J. Source: Annales D'endocrinologie. 1980 May-June; 41(3): 251-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7416714

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Further evidence that insulin metabolism is a major determinant of peripheral insulin response to oral glucose in subjects with mild glucose intolerance. Author(s): Bonora E, Zavaroni I, Manicardi V, Coscelli C, Butturini U. Source: J Endocrinol Invest. 1986 October; 9(5): 371-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3540080

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Further support for heterogeneity of insulin response and insulin sensitivity in nonobese subjects with glucose intolerance. Author(s): Ratzmann KP, Witt S, Schulz B. Source: Acta Endocrinol (Copenh). 1983 March; 102(3): 410-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6338676

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Future glucose intolerance possibly manifest in youth. Author(s): King H, Alpers M, Finch C, Zimmet P. Source: Lancet. 1989 November 4; 2(8671): 1098-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2572818

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Glucose intolerance after massive liver resection in man and other mammals. Author(s): Ida T, Ozawa K, Honjo I. Source: American Journal of Surgery. 1975 May; 129(5): 523-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1130591

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Glucose intolerance and aging. Author(s): DeFronzo RA. Source: Diabetes Care. 1981 July-August; 4(4): 493-501. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7049632

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Glucose intolerance and aging: evidence for tissue insensitivity to insulin. Author(s): Defronzo RA. Source: Diabetes. 1979 December; 28(12): 1095-101. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=510806

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Glucose intolerance and insulin resistance in aplastic anemia treated with oxymetholone. Author(s): Woodard TL, Burghen GA, Kitabchi AE, Wilimas JA. Source: The Journal of Clinical Endocrinology and Metabolism. 1981 November; 53(5): 905-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7026595

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Glucose intolerance associated with temporomandibular joint pain-dysfunction syndrome. Author(s): Oles RD. Source: Oral Surg Oral Med Oral Pathol. 1977 April; 43(4): 546-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=265482

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Glucose intolerance due to insulin resistance in patients with spinal cord injuries. Author(s): Duckworth WC, Solomon SS, Jallepalli P, Heckemeyer C, Finnern J, Powers A. Source: Diabetes. 1980 November; 29(11): 906-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7429029

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Glucose intolerance during diuretic therapy. Results of trial by the European Working Party on Hypertension in the Elderly. Author(s): Amery A, Berthaux P, Bulpitt C, Deruyttere M, de Schaepdryver A, Dollery C, Fagard R, Forette F, Hellemans J, Lund-Johansen P, Mutsers A, Tuomilehto J. Source: Lancet. 1978 April 1; 1(8066): 681-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=76223

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Glucose intolerance during pregnancy. I. A reappraisal of alleged screening criteria. Author(s): Granat M, Sharf M, Cooper A. Source: Obstetrics and Gynecology. 1979 February; 53(2): 157-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=418967

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Glucose intolerance during pregnancy. II. A comparative study of diagnostic screening methods. Author(s): Cooper A, Granat M, Sharf M. Source: Obstetrics and Gynecology. 1979 April; 53(4): 495-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=440654

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Glucose intolerance following chronic metabolic acidosis in man. Author(s): DeFronzo RA, Beckles AD. Source: The American Journal of Physiology. 1979 April; 236(4): E328-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=434194

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Glucose intolerance in alcoholism. Author(s): Sereny G, Endrenyi L, Devenyi P. Source: J Stud Alcohol. 1975 March; 36(3): 359-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=235678

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Glucose intolerance in hyperthyroidism: role of glucagon. Author(s): Kabadi UM, Eisenstein AB. Source: The Journal of Clinical Endocrinology and Metabolism. 1980 February; 50(2): 392-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6986398

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Glucose intolerance in Parkinson's disease. Author(s): Lipman IJ, Boykin ME, Flora RE. Source: J Chronic Dis. 1974 December; 27(11-12): 573-9. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4436423

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Glucose intolerance in the carcinoid syndrome. Author(s): Feldman JM, Plonk JW, Bivens CH, Lebovitz HE. Source: Diabetes. 1975 July; 24(7): 664-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=125668

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Glucose intolerance in the hemodialyzed patient: a brief overview. Author(s): Westervelt FB Jr. Source: Kidney International. Supplement. 1974 October; (1): 70-2. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4619140

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Glucose intolerance in uremia (A- and B-cell function during conservative and dialytic management. Author(s): Benedetti MM, Santeusanio F, Angeletti G, Filipponi P, Buoncristiani U, Brunetti P. Source: Acta Diabetol Lat. 1977 September-December; 14(5-6): 235-49. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=613688

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Glucose intolerance in uremia. Quantification of pancreatic beta cell sensitivity to glucose and tissue sensitivity to insulin. Author(s): DeFronzo RA, Tobin JD, Rowe JW, Andres R. Source: The Journal of Clinical Investigation. 1978 August; 62(2): 425-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=353075

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Glucose intolerance in uremia: site and mechanism. Author(s): DeFronzo RA, Alvestrand A. Source: The American Journal of Clinical Nutrition. 1980 July; 33(7): 1438-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6994471

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Glucose intolerance, diabetes mellitus and atherosclerosis; prospects for prevention. Author(s): Keen H. Source: Postgraduate Medical Journal. 1976 July; 52(609): 445-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=967763

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Glycohemoglobin. Its use in the follow-up of diabetes and diagnosis of glucose intolerance. Author(s): Lev-Ran A. Source: Archives of Internal Medicine. 1981 May; 141(6): 747-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7235783

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Healthy diet and lifestyle clustering and glucose intolerance. Author(s): Perry IJ. Source: The Proceedings of the Nutrition Society. 2002 November; 61(4): 543-51. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12691184

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Hemoglobin AIc as an indicator of the degree of glucose intolerance in diabetes. Author(s): Koenig RJ, Peterson CM, Kilo C, Cerami A, Williamson JR. Source: Diabetes. 1976 March; 25(3): 230-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1254113

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Hepatic dearterialisation induces glucose intolerance and inhibits insulin secretion in patients with liver malignancy. Author(s): Sjovall S, Ahren B. Source: The European Journal of Surgery = Acta Chirurgica. 1991 May; 157(5): 329-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1678646

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High glycosylated hemoglobin levels increase the risk of progression to diabetes mellitus in subjects with glucose intolerance. Author(s): Yoshinaga H, Kosaka K. Source: Diabetes Research and Clinical Practice. 1996 March; 31(1-3): 71-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8792104

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High incidence of glucose intolerance in Vogt-Koyanagi-Harada disease. Author(s): Yawata N, Nakamura S, Kijima M, Ikai N, Kanai M, Sugita M, Ohno S. Source: The British Journal of Ophthalmology. 1999 January; 83(1): 39-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10209432

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HLA type, islet cell antibodies, and glucose intolerance in cystic fibrosis. Author(s): Stutchfield PR, O'Halloran SM, Smith CS, Woodrow JC, Bottazzo GF, Heaf D. Source: Archives of Disease in Childhood. 1988 October; 63(10): 1234-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3058046

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Hypercholesterolemia in diabetes and glucose intolerance in the U.S. population. Author(s): Harris MI. Source: Diabetes Care. 1991 May; 14(5): 366-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2060448

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Hyperinsulinaemia in obesity is not accompanied by an increase in serum proinsulin/insulin ratio in groups of human subjects with and without glucose intolerance. Author(s): Shiraishi I, Iwamoto Y, Kuzuya T, Matsuda A, Kumakura S. Source: Diabetologia. 1991 October; 34(10): 737-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1959706

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Hyperinsulinemia in glucose intolerance: is it true? Author(s): Giugliano D, Quatraro A, Acampora R, De Rosa N, Ceriello A, D'Onofrio F. Source: J Endocrinol Invest. 1994 June; 17(6): 391-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7930385

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Hyperinsulinemia. A link between hypertension obesity and glucose intolerance. Author(s): Modan M, Halkin H, Almog S, Lusky A, Eshkol A, Shefi M, Shitrit A, Fuchs Z. Source: The Journal of Clinical Investigation. 1985 March; 75(3): 809-17. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3884667

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Hyperinsulinemia--a link between glucose intolerance, obesity, hypertension, dyslipoproteinemia, elevated serum uric acid and internal cation imbalance. Author(s): Modan M, Halkin H, Fuchs Z, Lusky A, Chetrit A, Segal P, Eshkol A, Almog S, Shefi M. Source: Diabete Metab. 1987 July; 13(3 Pt 2): 375-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3308568

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Hyperlipidemia and glucose intolerance in the post-renal transplant patient. Author(s): Markell MS, Armenti V, Danovitch G, Sumrani N. Source: Journal of the American Society of Nephrology : Jasn. 1994 February; 4(8 Suppl): S37-47. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8193294

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Hypertension and pre-eclampsia in women with gestational glucose intolerance. Author(s): Suhonen L, Teramo K. Source: Acta Obstetricia Et Gynecologica Scandinavica. 1993 May; 72(4): 269-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8389513

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Hypertension in Alaska Natives: association with overweight, glucose intolerance, diet and mechanized activity. Author(s): Murphy NJ, Schraer CD, Theile MC, Boyko EJ, Bulkow LR, Doty BJ, Lanier AP. Source: Ethnicity & Health. 1997 November; 2(4): 267-75. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9526689

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Hypertension in glucose intolerance and diabetes. Author(s): Jarrett RJ. Source: Journal of Internal Medicine. Supplement. 1991; 735: 85-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2043226

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Hypertension in the elderly is associated with impaired glucose metabolism independently of obesity and glucose intolerance. Author(s): Verza M, D'Avino M, Cacciapuoti F, Aceto E, D'Errico S, Varricchio M, Giugliano D. Source: Journal of Hypertension. Supplement : Official Journal of the International Society of Hypertension. 1988 November; 6(1): S45-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3063793

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Hyperthyroidism and glucose intolerance. Author(s): Ahren B. Source: Acta Med Scand. 1986; 220(1): 5-14. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3532696

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Hypertriglyceridemia in different degrees of glucose intolerance in a Finnish population-based study. Author(s): Salomaa VV, Tuomilehto J, Jauhiainen M, Korhonen HJ, Stengard J, Uusitupa M, Pitkanen M, Penttila I. Source: Diabetes Care. 1992 May; 15(5): 657-65. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1516486

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Hypokalemia, glucose intolerance, and hyperinsulinemia during diuretic therapy. Author(s): Plavinik FL, Rodrigues CI, Zanella MT, Ribeiro AB. Source: Hypertension. 1992 February; 19(2 Suppl): Ii26-9. Erratum In: Hypertension 1992 August; 20(2): 265. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1735589

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Hypophosphatemia and glucose intolerance: evidence for tissue insensitivity to insulin. Author(s): DeFronzo RA, Lang R. Source: The New England Journal of Medicine. 1980 November 27; 303(22): 1259-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6999353

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Immunosuppression in renal transplantation. Postoperative glucose intolerance was almost certainly underestimated. Author(s): Krentz AJ. Source: Bmj (Clinical Research Ed.). 1999 October 23; 319(7217): 1136-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10610150

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Impact of glucose intolerance and insulin resistance on cardiac structure and function: sex-related differences in the Framingham Heart Study. Author(s): Rutter MK, Parise H, Benjamin EJ, Levy D, Larson MG, Meigs JB, Nesto RW, Wilson PW, Vasan RS. Source: Circulation. 2003 January 28; 107(3): 448-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12551870

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Impact of the 1997 American Diabetes Association criteria on classification of glucose intolerance among Kuwaitis below 50 years of age. Author(s): Abdella N, Al Nakhi A, Al Arouj M, Assoussi A, Moussa M. Source: Acta Diabetologica. 1999 September; 36(3): 133-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10664317

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Impaired ('diabetic') insulin signaling and action occur in fat cells long before glucose intolerance--is insulin resistance initiated in the adipose tissue? Author(s): Smith U. Source: International Journal of Obesity and Related Metabolic Disorders : Journal of the International Association for the Study of Obesity. 2002 July; 26(7): 897-904. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12080441

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Impaired adaptation of first-phase insulin secretion in postmenopausal women with glucose intolerance. Author(s): Ahren B, Pacini G. Source: The American Journal of Physiology. 1997 October; 273(4 Pt 1): E701-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9357798

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Impaired feedback control of fat induced gastric inhibitory polypeptide (GIP) secretion by insulin in obesity and glucose intolerance. Author(s): Ebert R, Frerichs H, Creutzfeldt W. Source: European Journal of Clinical Investigation. 1979 April; 9(2 Pt 1): 129-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=111943

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Increased glucose intolerance related to digoxin treatment in patients with type 2 diabetes mellitus. Author(s): Spigset O, Mjorndal T. Source: Journal of Internal Medicine. 1999 October; 246(4): 419-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10583713

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Increased risk factors for coronary artery disease in Japanese subjects with hyperinsulinemia or glucose intolerance. Author(s): Yamada N, Yoshinaga H, Sakurai N, Shimano H, Gotoda T, Ohashi Y, Yazaki Y, Kosaka K. Source: Diabetes Care. 1994 February; 17(2): 107-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8137680

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Influences of increased oxidative stress on endothelial function, platelets function, and fibrinolysis in hypertension associated with glucose intolerance. Author(s): Tomiyama H, Kushiro T, Okazaki R, Yoshida H, Doba N, Yamashina A. Source: Hypertens Res. 2003 April; 26(4): 295-300. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12733697

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Inhibition of adipogenesis and development of glucose intolerance by soluble preadipocyte factor-1 (Pref-1). Author(s): Lee K, Villena JA, Moon YS, Kim KH, Lee S, Kang C, Sul HS. Source: The Journal of Clinical Investigation. 2003 February; 111(4): 453-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12588883

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Insulin levels and the natural history of glucose intolerance in Nauruans. Author(s): Dowse GK, Zimmet PZ, Collins VR. Source: Diabetes. 1996 October; 45(10): 1367-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8826973

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Insulin release, insulin sensitivity, and glucose intolerance. Author(s): Efendic S, Wajngot A, Cerasi E, Luft R. Source: Proceedings of the National Academy of Sciences of the United States of America. 1980 December; 77(12): 7425-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7012840

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Insulin resistance, glucose intolerance, and hyperinsulinemia in patients with microvascular angina. Author(s): Fuh MM, Jeng CY, Young MM, Sheu WH, Chen YD, Reaven GM. Source: Metabolism: Clinical and Experimental. 1993 September; 42(9): 1090-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8412759

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Insulin resistance, glucose intolerance, and hyperinsulinemia. Hypertriglyceridemia versus hypercholesterolemia. Author(s): Sheu WH, Shieh SM, Fuh MM, Shen DD, Jeng CY, Chen YD, Reaven GM. Source: Arterioscler Thromb. 1993 March; 13(3): 367-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8443140

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Insulin resistance, glucose intolerance, hyperinsulinemia and dyslipidemia in patients with angiographically demonstrated coronary artery disease. Author(s): Young MH, Jeng CY, Sheu WH, Shieh SM, Fuh MM, Chen YD, Reaven GM. Source: The American Journal of Cardiology. 1993 August 15; 72(5): 458-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8352190

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Insulin response to glucose and tolbutamide in "essential" versus "pancreatic" mild glucose intolerance. Author(s): Vague P, Ramahandridona G, Gerolami A. Source: Diabetes. 1974 November; 23(11): 896-901. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4430416

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Insulin responses in equivocal and definite diabetes, with special reference to subjects who had mild glucose intolerance but later developed definite diabetes. Author(s): Kosaka K, Hagura R, Kuzuya T. Source: Diabetes. 1977 October; 26(10): 944-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=908463

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Insulin secretory responses in patients with glucose intolerance due to extrapancreatic causes. Comparison with idiopathic diabetes mellitus. Author(s): Kosaka K, Kuzuya T, Hagura R, Akanuma Y, Kanazawa Y. Source: Endocrinol Jpn. 1981 August; 28(4): 487-98. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6763894

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Interactions between insulin resistance and insulin secretion in the development of glucose intolerance. Author(s): Cavaghan MK, Ehrmann DA, Polonsky KS. Source: The Journal of Clinical Investigation. 2000 August; 106(3): 329-33. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10930434

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Internalized racism is associated with glucose intolerance among Black Americans in the U.S. Virgin Islands. Author(s): Tull ES, Chambers EC. Source: Diabetes Care. 2001 August; 24(8): 1498. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11473095

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Letter: Glucose intolerance and diuretics. Author(s): Ram CV. Source: Lancet. 1976 May 29; 1(7970): 1186. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=58231

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Letter: Glucose intolerance and peripheral glucose uptake in acutely intoxicated alcoholics. Author(s): Eriksson CE, Hed R, Lindblad LE, Nygren A, Sundblad L. Source: Lancet. 1974 April 27; 1(7861): 811-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4132746

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Letter: Glucose intolerance in pulmonary. Author(s): Nichols GP. Source: Am Rev Respir Dis. 1974 September; 110(3): 368. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4414239

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Letter: Pyridoxine and oestrogen-induced glucose intolerance. Author(s): Cornish EJ, Tesoriero W. Source: British Medical Journal. 1975 September 13; 3(5984): 649-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1164654

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Limitations of glycosylated haemoglobin as an index of glucose intolerance. Author(s): Snehalatha C, Ramachandran A, Satyavani K, Vijay V. Source: Diabetes Research and Clinical Practice. 2000 February; 47(2): 129-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10670913

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Limited insulin responses in older non-obese control subjects without glucose intolerance. Author(s): Corredor DG, Jung Y, Khurana RC, Creech R, Christy W, Nealis T, Danowski TS. Source: Pol Med Sci Hist Bull. 1971 January; 14(1): 13-20. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5100384

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Lipids, glucose intolerance and vascular disease: the Framingham Study. Author(s): Wilson PW, Kannel WB, Anderson KM. Source: Monogr Atheroscler. 1985; 13: 1-11. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4088270

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Lipoprotein response to exercise training and a low-fat diet in older subjects with glucose intolerance. Author(s): Hughes VA, Fiatarone MA, Ferrara CM, McNamara JR, Charnley JM, Evans WJ. Source: The American Journal of Clinical Nutrition. 1994 April; 59(4): 820-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8147325

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Lipoprotein(a) levels in hemodialysis patients: relation to glucose intolerance and hemodialysis duration. Author(s): Fiorini F, Masturzo P, Mij M, Bertolini S. Source: Nephron. 1995; 70(4): 500-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7477660

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Lithium carbonate-induced nephrogenic diabetes insipidus and glucose intolerance. Author(s): Martinez-Maldonado M, Terrell J. Source: Archives of Internal Medicine. 1973 December; 132(6): 881-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4757260

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Long-term (5-year) effects of a reduced-fat diet intervention in individuals with glucose intolerance. Author(s): Swinburn BA, Metcalf PA, Ley SJ. Source: Diabetes Care. 2001 April; 24(4): 619-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11315819

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Long-term effects of fluoxetine on glycemic control in obese patients with noninsulin-dependent diabetes mellitus or glucose intolerance: influence on muscle glycogen synthase and insulin receptor kinase activity. Author(s): Breum L, Bjerre U, Bak JF, Jacobsen S, Astrup A. Source: Metabolism: Clinical and Experimental. 1995 December; 44(12): 1570-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8786726

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Long-term risk of malignant neoplasm associated with gestational glucose intolerance. Author(s): Tanko LB, Bagger YZ, Christiansen C. Source: Cancer. 2004 June 15; 100(12): 2680-1; Author Reply 2681. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15197812

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Long-term risk of malignant neoplasm associated with gestational glucose intolerance. Author(s): Dawson SI. Source: Cancer. 2004 January 1; 100(1): 149-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14692035

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Low birth weight, family history of diabetes, and glucose intolerance in Swedish middle-aged men. Author(s): Carlsson S, Persson PG, Alvarsson M, Efendic S, Norman A, Svanstrom L, Ostenson CG, Grill V. Source: Diabetes Care. 1999 July; 22(7): 1043-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10388964

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Making things easier is not so easy. The 1997 American Diabetes Association criteria and glucose intolerance. Author(s): Aguilar-Salinas CA, Garcia-Garcia E, Lerman-Garber I, Gomez-Perez FJ, Rull JA. Source: Diabetes Care. 1998 June; 21(6): 1027-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9614628

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Maternal ante-natal parameters as predictors of persistent postnatal glucose intolerance: a comparative study between Afro-Caribbeans, Asians and Caucasians. Author(s): Sinha B, Brydon P, Taylor RS, Hollins A, Munro A, Jenkins D, Dunne F. Source: Diabetic Medicine : a Journal of the British Diabetic Association. 2003 May; 20(5): 382-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12752487

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Maternal fructosamine and glycosylated haemoglobin in the prediction of gestational glucose intolerance. Author(s): Aziz NL, Abdelwahab S, Moussa M, Georgy M. Source: Clin Exp Obstet Gynecol. 1992; 19(4): 235-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1294344

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Maternal glucose intolerance and the subcutaneous terbutaline pump. Author(s): Lindenbaum C, Ludmir J, Teplick FB, Cohen AW, Samuels P. Source: American Journal of Obstetrics and Gynecology. 1992 March; 166(3): 925-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1550166

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Maternal obesity and glucose intolerance during pregnancy among MexicanAmericans. Author(s): Kieffer EC. Source: Paediatric and Perinatal Epidemiology. 2000 January; 14(1): 14-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10703030

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Mechanism of glucose intolerance during fasting: differences between lean and obese subjects. Author(s): Goschke H. Source: Metabolism: Clinical and Experimental. 1977 October; 26(10): 1147-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=895529

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Mechanism of glucose intolerance in cystic fibrosis. Author(s): Clodi HP, Pfeiffer EF. Source: The New England Journal of Medicine. 1970 February 19; 282(8): 455-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5412202

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Mechanisms associating body fat distribution to glucose intolerance and diabetes mellitus: window with a view. Author(s): Kissebah AH, Peiris AN, Evans DJ. Source: Acta Med Scand Suppl. 1988; 723: 79-89. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3293360

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Mechanisms of epinephrine-induced glucose intolerance in normal humans. Author(s): Sacca L, Vigorito C, Cicala M, Ungaro B, Sherwin RS. Source: The Journal of Clinical Investigation. 1982 February; 69(2): 284-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7035494

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Mechanisms of glucose intolerance during triglyceride infusion. Author(s): Rigalleau V, Beylot M, Pachiaudi C, Guillot C, Deleris G, Gin H. Source: The American Journal of Physiology. 1998 October; 275(4 Pt 1): E641-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9755083

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Medical pathology conference. A 54-year-old man with progressive glucose intolerance. Author(s): Garcia JH, Reynertson R, Breatnach E, Herrera GA. Source: Ala J Med Sci. 1985 July; 22(3): 281-7. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2992306

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Metabolic disturbances increasing the risk of coronary heart disease during diureticbased antihypertensive therapy: lipid alterations and glucose intolerance. Author(s): Ames RP. Source: American Heart Journal. 1983 November; 106(5 Pt 2): 1207-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6637786

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Metabolic effects of physical training in subjects with oral glucose intolerance. Author(s): Erle G, Cortesi S, Zen F, Mingardi R, Sicolo N. Source: International Journal of Sports Medicine. 1985 October; 6(5): 303-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4055193

76

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More on thyroid status in patients with chronic renal failure: effect of glucose intolerance on serum reverse T3. Author(s): De Marchi S, Cecchin E, Tesio F, Borean M. Source: Clinical Nephrology. 1984 May; 21(5): 303-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6734000

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Natural history of glucose intolerance in obesity. A ten year observation. Author(s): Toeller M, Gries FA, Dannehl K. Source: Int J Obes. 1982; 6 Suppl 1: 145-9. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6749720

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Neonatal morbidities in infants of mothers with glucose intolerance in pregnancy. Author(s): Widness JA, Cowett RM, Coustan DR, Carpenter MW, Oh W. Source: Diabetes. 1985 June; 34 Suppl 2: 61-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3996769

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Nifedipine vs. enalapril in treatment of hypertensive patients with glucose intolerance. Author(s): Andronico G, Piazza G, Mangano MT, Mule G, Carone MB, Cerasola G. Source: Journal of Cardiovascular Pharmacology. 1991; 18 Suppl 10: S52-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1725004

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Nitrogen utilization, enzyme activity, glucose intolerance and leukocyte chemotaxis in human experimental zinc depletion. Author(s): Baer MT, King JC, Tamura T, Margen S, Bradfield RB, Weston WL, Daugherty NA. Source: The American Journal of Clinical Nutrition. 1985 June; 41(6): 1220-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3890515

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Nodular glomerulosclerosis without glucose intolerance: long-term follow-up. Author(s): Gonzalo A, Navarro J, Mampaso F, Ortuno J. Source: Nephron. 1994; 66(4): 481-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8015658

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Non-insulin-dependent diabetes mellitus, glucose intolerance, blood pressure, hypertension, and antihypertensive drugs. Author(s): Jarrett RJ, Fitzgerald AP. Source: Diabetic Medicine : a Journal of the British Diabetic Association. 1994 AugustSeptember; 11(7): 646-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7955988

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Obesity, glucose intolerance and diabetes and their links to cardiovascular disease. Implications for laboratory medicine. Author(s): Dominiczak MH. Source: Clinical Chemistry and Laboratory Medicine : Cclm / Fescc. 2003 September; 41(9): 1266-78. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14598880

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Obesity, glucose intolerance, hyperinsulinemia, and response to antihypertensive drugs. Author(s): Modan M, Almog S, Fuchs Z, Chetrit A, Lusky A, Halkin H. Source: Hypertension. 1991 April; 17(4): 565-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2013483

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Obesity, lipids, and glucose intolerance. The Framingham Study. Author(s): Kannel WB, Gordon T, Castelli WP. Source: The American Journal of Clinical Nutrition. 1979 June; 32(6): 1238-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=443188

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Obesity, very low density lipoproteins, and glucose intolerance over fourteen years: The Framingham Study. Author(s): Wilson PW, McGee DL, Kannel WB. Source: American Journal of Epidemiology. 1981 November; 114(5): 697-704. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7304597

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Occult glucose intolerance: incidence in a general population. Author(s): Searcy RL, Low EM. Source: Calif Med. 1967 May; 106(5): 364-7. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6046045

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Occurrence of intercapillary nodular glomerulosclerosis in the absence of glucose intolerance. Author(s): Kanwar YS, Garces J, Molitch ME. Source: American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation. 1990 March; 15(3): 281-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2407111

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Office guide to diagnosis and classification of diabetes mellitus and other categories of glucose intolerance. Author(s): Shuman CR, Spratt IL. Source: Diabetes Care. 1981 March-April; 4(2): 335. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7215090

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On the role of islet amyloid polypeptide in glucose intolerance and anorexia of pancreatic cancer. Author(s): Herrington MK, Arnelo U, Permert J. Source: Pancreatology : Official Journal of the International Association of Pancreatology (Iap). [et Al.]. 2001; 1(3): 267-74. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12120206

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Oral contraceptive use: prospective follow-up of women with suspected glucose intolerance. Author(s): Duffy TJ, Ray R. Source: Contraception. 1984 September; 30(3): 197-208. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6509976

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Outcome of diabetic pregnancy and glucose intolerance in pregnancy: an audit of fetal loss in Newcastle General Hospital 1977-1990. Author(s): Hawthorne G, Snodgrass A, Tunbridge M. Source: Diabetes Research and Clinical Practice. 1994 October; 25(3): 183-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7851273

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Pakistan National Diabetes Survey prevalence of glucose intolerance and associated factors in North West at Frontier Province (NWFP) of Pakistan. Author(s): Shera AS, Rafique G, Khwaja IA, Baqai S, Khan IA, King H, Ahmed KI. Source: J Pak Med Assoc. 1999 September; 49(9): 206-11. Erratum In: Jpma J Pak Med Assoc 1999 December; 49(12): 317. Ahmed Ki[corrected to Khwaja Ia]. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10646320

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Pakistan National Diabetes Survey: prevalence of glucose intolerance and associated factors in Baluchistan province. Author(s): Shera AS, Rafique G, Khawaja IA, Baqai S, King H. Source: Diabetes Research and Clinical Practice. 1999 April; 44(1): 49-58. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10414940

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Parallel changes of proinsulin and islet amyloid polypeptide in glucose intolerance. Author(s): MacNamara CM, Barrow BA, Manley SE, Levy JC, Clark A, Turner RC. Source: Diabetes Research and Clinical Practice. 2000 October; 50(2): 117-26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10960722

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Pathogenesis of glucose intolerance in uremia. Author(s): DeFronzo RA. Source: Metabolism: Clinical and Experimental. 1978 December; 27(12 Suppl 2): 1866-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=723638

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Pathogenic factors of glucose intolerance in obese Japanese adolescents with type 2 diabetes. Author(s): Kobayashi K, Amemiya S, Higashida K, Ishihara T, Sawanobori E, Kobayashi K, Mochizuki M, Kikuchi N, Tokuyama K, Nakazawa S. Source: Metabolism: Clinical and Experimental. 2000 February; 49(2): 186-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10690942

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Patterns of glucose intolerance and free fatty acid behavior in viral hepatitis. Author(s): Granot C, Bar-On H, Shafrir E. Source: Isr J Med Sci. 1981 January; 17(1): 12-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7007283

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PAX6 mutation as a genetic factor common to aniridia and glucose intolerance. Author(s): Yasuda T, Kajimoto Y, Fujitani Y, Watada H, Yamamoto S, Watarai T, Umayahara Y, Matsuhisa M, Gorogawa S, Kuwayama Y, Tano Y, Yamasaki Y, Hori M. Source: Diabetes. 2002 January; 51(1): 224-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11756345

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Perinatal significance of diagnosing glucose intolerance during pregnancy with portable glucose meter. Author(s): Jakobi P, Weissman A, Egozi J, Minuchin O, Geva A. Source: Journal of Perinatal Medicine. 2003; 31(2): 140-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12747230

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Peripheral neuropathy in myotonic dystrophy. Relation to glucose intolerance. Author(s): Olson ND, Jou MF, Quast JE, Nuttall FQ. Source: Archives of Neurology. 1978 November; 35(11): 741-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=718472

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Placental weight to birthweight ratio is increased in mild gestational glucose intolerance. Author(s): Lao TT, Lee CP, Wong WM. Source: Placenta. 1997 March-April; 18(2-3): 227-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9089786

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Plasma insulin; insulin resistance and glucose intolerance in children with bilharzial hepatic fibrosis. Author(s): Zaki K, Kantoosh M, Hamam MA, Shoheib S, Mikhail N, Nour H, Zaki F. Source: Hepatogastroenterology. 1980 December; 27(6): 417-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7009363

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Postpartum glucose intolerance in Chinese women with gestational diabetes. Author(s): Yang X, Hsu-Hage BH, Dong L, Zhang H, Zhang C, Zhang Y. Source: Diabetic Medicine : a Journal of the British Diabetic Association. 2003 August; 20(8): 687-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12873301

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Preliminary report: BGLIIA-BGLIIB haplotype of growth hormone cluster is associated with glucose intolerance in non-insulin-dependent diabetes mellitus and with growth hormone deficit in growth retardation. Author(s): Bottini E, Lucarelli P, Amante A, Saccucci P, Gloria-Bottini F. Source: Metabolism: Clinical and Experimental. 2002 January; 51(1): 1-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11782864

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Prevalence and concomitants of glucose intolerance in European obese children and adolescents. Author(s): Invitti C, Guzzaloni G, Gilardini L, Morabito F, Viberti G. Source: Diabetes Care. 2003 January; 26(1): 118-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12502667

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Prevalence and determinants of diabetes mellitus and glucose intolerance in a Canarian Caucasian population - comparison of the 1997 ADA and the 1985 WHO criteria. The Guia Study. Author(s): de Pablos-Velasco PL, Martinez-Martin FJ, Rodriguez-Perez F, Ania BJ, Losada A, Betancor P; Guia Study. Source: Diabetic Medicine : a Journal of the British Diabetic Association. 2001 March; 18(3): 235-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11318846

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Prevalence of diabetes and glucose intolerance in 199 offspring of thirty-seven conjugal diabetic parents. Author(s): Tattersal RB, Fajans SS. Source: Diabetes. 1975 May; 24(5): 452-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1126589

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Prevalence of glucose intolerance among Malays in Brunei. Author(s): van Eekelen A, Stokvis-Brantsma H, Frolich M, Smelt AH, Stokvis H. Source: Diabetes Care. 2000 September; 23(9): 1435-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10977050

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Prevalence of glucose intolerance among Native Hawaiians in two rural communities. Native Hawaiian Health Research (NHHR) Project. Author(s): Grandinetti A, Chang HK, Mau MK, Curb JD, Kinney EK, Sagum R, Arakaki RF. Source: Diabetes Care. 1998 April; 21(4): 549-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9571341

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Prevalence of glucose intolerance in urban and rural communities in Saudi Arabia. Author(s): Al-Nuaim AR. Source: Diabetic Medicine : a Journal of the British Diabetic Association. 1997 July; 14(7): 595-602. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9223399

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Preventing cardiovascular disease in diabetes and glucose intolerance: evidence and implications for care. Author(s): Rennert NJ, Charney P. Source: Primary Care. 2003 September; 30(3): 569-92. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14692202

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QTc duration is associated with levels of insulin and glucose intolerance. The Zutphen Elderly Study. Author(s): Dekker JM, Feskens EJ, Schouten EG, Klootwijk P, Pool J, Kromhout D. Source: Diabetes. 1996 March; 45(3): 376-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8593946

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Re: "Weight history, glucose intolerance, and insulin levels in middle-aged Swedish men". Author(s): Longnecker MP, Michalek JE. Source: American Journal of Epidemiology. 1999 August 15; 150(4): 430-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10453822

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Recombinant human betacellulin promotes the neogenesis of beta-cells and ameliorates glucose intolerance in mice with diabetes induced by selective alloxan perfusion. Author(s): Yamamoto K, Miyagawa J, Waguri M, Sasada R, Igarashi K, Li M, Nammo T, Moriwaki M, Imagawa A, Yamagata K, Nakajima H, Namba M, Tochino Y, Hanafusa T, Matsuzawa Y. Source: Diabetes. 2000 December; 49(12): 2021-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11118003

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Reduced glucose effectiveness as a feature of glucose intolerance: evidence in elderly type-2 diabetic subjects. Author(s): Viviani GL, Pacini G. Source: Aging (Milano). 1999 June; 11(3): 169-75. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10476312

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Rehydration of moderately dehydrated children with transient glucose intolerance using rice oral rehydration solution. Author(s): Yurdakok K, Ozmert E, Yalcin SS, Coskun T. Source: Acta Paediatrica (Oslo, Norway : 1992). 1999 January; 88(1): 34-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10090544

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Rehydration of two patients with secondary glucose intolerance by using rice-oral rehydration solution (R-ORS) Author(s): Yurdakok K, Ozmert E. Source: Journal of Pediatric Gastroenterology and Nutrition. 1996 November; 23(4): 50910. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8956201

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Relation of high blood pressure to glucose intolerance, plasma lipids and educational status in an Arabian Gulf population. Author(s): Al-Mahroos F, Al-Roomi K, McKeigue PM. Source: International Journal of Epidemiology. 2000 February; 29(1): 71-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10750606

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Relations between deletion polymorphism of the angiotensin-converting enzyme gene and insulin resistance, glucose intolerance, hyperinsulinemia, and dyslipidemia. Author(s): Katsuya T, Horiuchi M, Chen YD, Koike G, Pratt RE, Dzau VJ, Reaven GM. Source: Arteriosclerosis, Thrombosis, and Vascular Biology. 1995 June; 15(6): 779-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7773733

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Relationship between height, glucose intolerance, and hypertension in an urban African black adult population: a case for the "thrifty phenotype" hypothesis? Author(s): Olatunbosun ST, Bella AF. Source: Journal of the National Medical Association. 2000 June; 92(6): 265-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10918760

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Relationship of glucose intolerance to coronary risk in Afro-Caribbeans compared with Europeans. Author(s): Chaturvedi N, McKeigue PM, Marmot MG. Source: Diabetologia. 1994 August; 37(8): 765-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7988778

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Relationship of the angiotensin-converting enzyme gene polymorphism to glucose intolerance, insulin resistance, and hypertension in NIDDM. Author(s): Huang XH, Rantalaiho V, Wirta O, Pasternack A, Koivula T, Hiltunen T, Nikkari T, Lehtimaki T. Source: Human Genetics. 1998 March; 102(3): 372-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9544854

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Relationships between maternal glucose intolerance and neonatal blood glucose. Author(s): Haworth JC, Dilling LA. Source: The Journal of Pediatrics. 1976 November; 89(5): 810-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=978332

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Relative importance of maternal constitutional factors and glucose intolerance of pregnancy in the development of newborn macrosomia. Author(s): Okun N, Verma A, Mitchell BF, Flowerdew G. Source: The Journal of Maternal-Fetal Medicine. 1997 September-October; 6(5): 285-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9360188

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Reproducibility of hemoglobin AIc and sensitivity to various degrees of glucose intolerance. Author(s): Dunn PJ, Cole RA, Soeldner JS, Gleason RE. Source: Annals of Internal Medicine. 1979 September; 91(3): 390-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=475166

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Reversal of diet-induced glucose intolerance by hepatic expression of a variant glycogen-targeting subunit of protein phosphatase-1. Author(s): Gasa R, Clark C, Yang R, DePaoli-Roach AA, Newgard CB. Source: The Journal of Biological Chemistry. 2002 January 11; 277(2): 1524-30. Epub 2001 November 13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11707447

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Risk factors for death in men with glucose intolerance. Author(s): Jarrett RJ. Source: Bmj (Clinical Research Ed.). 1993 August 28; 307(6903): 569. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8401007

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Risk factors for glucose intolerance in active acromegaly. Author(s): Kreze A, Kreze-Spirova E, Mikulecky M. Source: Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Medicas E Biologicas / Sociedade Brasileira De Biofisica. [et Al.]. 2001 November; 34(11): 1429-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11668352

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Role of glucose intolerance in cardiac diastolic function in essential hypertension. Author(s): Nagano N, Nagano M, Yo Y, Iiyama K, Higaki J, Mikami H, Ogihara T. Source: Hypertension. 1994 June; 23(6 Pt 2): 1002-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8206582

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Role of hyperinsulinemia and glucose intolerance in the pathogenesis of nonalcoholic fatty liver in patients with normal body weight. Author(s): Lee JH, Rhee PL, Lee JK, Lee KT, Kim JJ, Koh KC, Paik SW, Rhee JC, Choi KW. Source: Korean J Intern Med. 1998 February; 13(1): 12-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9538625

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Role of insulin in the pathogenesis of hypertension associated with glucose intolerance. Author(s): Takahashi H, Nakanishi T, Nishimura M, Fukumitsu S, Yoshimura M. Source: Clinical and Experimental Hypertension (New York, N.Y. : 1993). 1993 May; 15(3): 575-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8490597

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Roles of insulin resistance and beta-cell dysfunction in the pathogenesis of glucose intolerance in cystic fibrosis. Author(s): Austin A, Kalhan SC, Orenstein D, Nixon P, Arslanian S. Source: The Journal of Clinical Endocrinology and Metabolism. 1994 July; 79(1): 80-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8027259

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Screening for glucose intolerance in siblings of children with diabetes. Author(s): Rosenbloom AL, Bianchi R, Chin FT. Source: Metabolism: Clinical and Experimental. 1973 February; 22(2): 351-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4687960

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Screening for insulin receptor gene DNA polymorphisms associated with glucose intolerance in a Scandinavian population. Author(s): Sten-Linder M, Vilhelmsdotter S, Wedell A, Stern I, Pollare T, Arner P, Efendic S, Luft R, Luthman H. Source: Diabetologia. 1991 April; 34(4): 265-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1676686

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Secondary hyperparathyroidism and glucose intolerance in children with uremia. Author(s): Mak RH, Turner C, Haycock GB, Chantler C. Source: Kidney International. Supplement. 1983 December; 16: S128-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6588242

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Secondary syphilis presenting with arthritis, hepatitis, and glucose intolerance. Author(s): Williams WC, Marion GS. Source: The Journal of Family Practice. 1987 November; 25(5): 509-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3681210

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Senile cataract and glucose intolerance: the Israel Study of glucose Intolerance Obesity and Hypertension (The Israel GOH Study). Author(s): Karasik A, Modan M, Halkin H, Treister G, Fuchs Z, Lusky A. Source: Diabetes Care. 1984 January-February; 7(1): 52-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6705665

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Sepsis, glucose intolerance, and protein malnutrition: a metabolic paradox. Author(s): Dahn M, Kirkpatrick JR, Bouwman D. Source: Archives of Surgery (Chicago, Ill. : 1960). 1980 December; 115(12): 1415-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6778457

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Serum reverse T3 assay for predicting glucose intolerance in uremic patients on dialysis therapy. Author(s): De Marchi S, Cecchin E, Villalta D, Tesio F. Source: Clinical Nephrology. 1987 April; 27(4): 189-98. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3581526

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Should all pregnant women be screened for gestational glucose intolerance? Author(s): Ales KL, Santini DL. Source: Lancet. 1989 May 27; 1(8648): 1187-91. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2566747

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Should we treat minor degrees of glucose intolerance in pregnancy? Author(s): Bonomo M, Gandini ML, Farina A, Bonfadini E, Pisoni MP, Prudenziati A, Mion E, Greco P. Source: Ann Ist Super Sanita. 1997; 33(3): 393-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9542269

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Size at birth and glucose intolerance in a relatively genetically homogeneous, highbirth weight population. Author(s): Birgisdottir BE, Gunnarsdottir I, Thorsdottir I, Gudnason V, Benediktsson R. Source: The American Journal of Clinical Nutrition. 2002 August; 76(2): 399-403. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12145013

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Sleep-disordered breathing, glucose intolerance, and insulin resistance. Author(s): Punjabi NM, Ahmed MM, Polotsky VY, Beamer BA, O'Donnell CP. Source: Respiratory Physiology & Neurobiology. 2003 July 16; 136(2-3): 167-78. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12853008

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Smoking, lipids, glucose intolerance, and blood pressure as risk factors for peripheral atherosclerosis compared with ischemic heart disease in the Edinburgh Artery Study. Author(s): Fowkes FG, Housley E, Riemersma RA, Macintyre CC, Cawood EH, Prescott RJ, Ruckley CV. Source: American Journal of Epidemiology. 1992 February 15; 135(4): 331-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1550087

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Somatostatin and diabetes mellitus: the role of glucagon in diabetic hyperglycemia and glucose intolerance. Author(s): Wahren J. Source: Scandinavian Journal of Clinical and Laboratory Investigation. 1976 October; 36(6): 497-503. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1006141

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Standardized comparison of glucose intolerance in west African-origin populations of rural and urban Cameroon, Jamaica, and Caribbean migrants to Britain. Author(s): Mbanya JC, Cruickshank JK, Forrester T, Balkau B, Ngogang JY, Riste L, Forhan A, Anderson NM, Bennett F, Wilks R. Source: Diabetes Care. 1999 March; 22(3): 434-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10097925

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Studies of glucose intolerance in cirrhosis of the liver. Author(s): Shankar TP, Solomon SS, Duckworth WC, Himmelstein S, Gray S, Jerkins T, Bobal MA, Iyer RS. Source: The Journal of Laboratory and Clinical Medicine. 1983 October; 102(4): 459-69. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6352838

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Studies of glucose intolerance in septic injured patients. Author(s): Gump FE, Long C, Killian P, Kinney JM. Source: The Journal of Trauma. 1974 May; 14(5): 378-88. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4823949

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Studies on glucose intolerance in chronic renal failure: estimation of insulin sensitivity before and after initiation of hemodialysis. Author(s): Oshida Y, Sato Y, Shiraishi S, Sakamoto N. Source: Clinical Nephrology. 1987 July; 28(1): 35-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3304745

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Study of the effect of changing glucose, insulin, and insulin-like growth factor-I levels on serum corticosteroid binding globulin in lean, obese, and obese subjects with glucose intolerance. Author(s): Fernandez-Real JM, Pugeat M, Emptoz-Bonneton A, Ricart W. Source: Metabolism: Clinical and Experimental. 2001 October; 50(10): 1248-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11586502

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Subclinical states of glucose intolerance and risk of death in the U.S. Author(s): Saydah SH, Loria CM, Eberhardt MS, Brancati FL. Source: Diabetes Care. 2001 March; 24(3): 447-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11289466

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Targeted disruption of the glucose transporter 4 selectively in muscle causes insulin resistance and glucose intolerance. Author(s): Zisman A, Peroni OD, Abel ED, Michael MD, Mauvais-Jarvis F, Lowell BB, Wojtaszewski JF, Hirshman MF, Virkamaki A, Goodyear LJ, Kahn CR, Kahn BB. Source: Nature Medicine. 2000 August; 6(8): 924-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10932232

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Teenage pregnancy. BMI and patterns in weight gain and their effect on glucose intolerance. Author(s): Kurzel RB. Source: Annals of the New York Academy of Sciences. 1997 May 28; 817: 365-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9239208

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The association of physical activity with obesity, fat distribution and glucose intolerance in Pima Indians. Author(s): Kriska AM, LaPorte RE, Pettitt DJ, Charles MA, Nelson RG, Kuller LH, Bennett PH, Knowler WC. Source: Diabetologia. 1993 September; 36(9): 863-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8405759

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The genetics of the glucose intolerance disorders. Author(s): Rotter JI, Rimoin DL. Source: The American Journal of Medicine. 1981 January; 70(1): 116-26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7457485

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The glucose intolerance of acute pancreatitis: hormonal response to arginine. Author(s): Solomon SS, Duckworth WC, Jallepalli P, Bobal MA, Iyer R. Source: Diabetes. 1980 January; 29(1): 22-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6991312

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The impact of impaired insulin release and insulin resistance on glucose intolerance after renal transplantation. Author(s): Hjelmesaeth J, Hagen M, Hartmann A, Midtvedt K, Egeland T, Jenssen T. Source: Clinical Transplantation. 2002 December; 16(6): 389-96. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12437616

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The negative association between traditional physical activities and the prevalence of glucose intolerance in Alaska Natives. Author(s): Adler AI, Boyko EJ, Schraer CD, Murphy NJ. Source: Diabetic Medicine : a Journal of the British Diabetic Association. 1996 June; 13(6): 555-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8799660

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The postprandial state: mechanisms of glucose intolerance. Author(s): Dinneen SF. Source: Diabetic Medicine : a Journal of the British Diabetic Association. 1997 August; 14 Suppl 3: S19-24. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9272609

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The prevalence of three major risk factors of cardiovascular disease: (glucose intolerance, hypertension, hyperlipoproteinaemia) in a sample of Thai social class 1. Author(s): Viseshakul D, Premwatana P, Chulrojanamontri V, Kewsiri D. Source: J Med Assoc Thai. 1979 March; 62(3): 116-21. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=429940

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The relationship between insulin resistance and insulin secretion in Japanese subjects with borderline glucose intolerance. Author(s): Wasada T, Arii H, Kuroki H, Saeki A, Katsumori K, Saito S, Omori Y. Source: Diabetes Research and Clinical Practice. 1995 October; 30(1): 53-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8745206

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The role of apolipoprotein E and glucose intolerance in gallstone disease in middle aged subjects. Author(s): Niemi M, Kervinen K, Rantala A, Kauma H, Paivansalo M, Savolainen MJ, Lilja M, Kesaniemi YA. Source: Gut. 1999 April; 44(4): 557-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10075965

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The role of growth hormone in the glucose intolerance of uremia. Author(s): DeFronzo RA, Tobin J, Boden G, Andres R. Source: Acta Diabetol Lat. 1979 October-December; 16(4): 279-86. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=399149

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The role of obesity in the association of cardiovascular risk factors and glucose intolerance in small Japanese and North American communities. Author(s): Adachi H, Goetz FC, Jacobs DR, Tsuruta M, Hirai Y, Fujiura Y, Imaizumi T. Source: Diabetes Research and Clinical Practice. 2000 July; 49(1): 41-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10808062

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The severity of periodontal disease is associated with the development of glucose intolerance in non-diabetics: the Hisayama study. Author(s): Saito T, Shimazaki Y, Kiyohara Y, Kato I, Kubo M, Iida M, Koga T. Source: Journal of Dental Research. 2004 June; 83(6): 485-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15153457

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Thyroid hormone excess and glucose intolerance. Author(s): Dimitriadis GD, Raptis SA. Source: Experimental and Clinical Endocrinology & Diabetes : Official Journal, German Society of Endocrinology [and] German Diabetes Association. 2001; 109 Suppl 2: S22539. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11460573

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Tissue glycogen content and glucose intolerance. Author(s): Kasuga M, Ogawa W, Ohara T. Source: The Journal of Clinical Investigation. 2003 May; 111(9): 1282-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12727918

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Transient oculomotor nerve palsy. Association with thiazide-induced glucose intolerance. Author(s): Miller NR, Moses H. Source: Jama : the Journal of the American Medical Association. 1978 October 20; 240(17): 1887-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=691201

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Treatment of glucose intolerance in pregnancy: staged diabetes management. Author(s): Mazze RS. Source: Int J Clin Pharmacol Ther Toxicol. 1993 October; 31(10): 497-505. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8262688

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Trends in pulmonary function in patients with cystic fibrosis correlate with the degree of glucose intolerance at baseline. Author(s): Milla CE, Warwick WJ, Moran A. Source: American Journal of Respiratory and Critical Care Medicine. 2000 September; 162(3 Pt 1): 891-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10988101

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Trp64Arg mutation of beta 3-adrenergic receptor and insulin sensitivity in subjects with glucose intolerance. Author(s): Arii K, Suehiro T, Yamamoto M, Ito H, Ikeda Y, Nakauchi Y, Hashimoto K. Source: Intern Med. 1997 September; 36(9): 603-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9313101

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Ultrasonographic manifestations of carotid atherosclerosis and glucose intolerance in elderly eastern Finnish men. Author(s): Tuomilehto J, Qiao Q, Salonen R, Nissinen A, Salonen JT. Source: Diabetes Care. 1998 August; 21(8): 1349-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9702446

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Undiagnosed glucose intolerance encountered in clinical practice: reappraisal of the use of the oral glucose tolerance test. Author(s): Hwu CM, Kwok CF, Ku BI, Lin YT, Lee YS, Hsiao LC, Lee SH, Ho LT. Source: Zhonghua Yi Xue Za Zhi (Taipei). 2001 August; 64(8): 435-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11720141

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Undiagnosed glucose intolerance in the community: the Isle of Ely Diabetes Project. Author(s): Williams DR, Wareham NJ, Brown DC, Byrne CD, Clark PM, Cox BD, Cox LJ, Day NE, Hales CN, Palmer CR, et al. Source: Diabetic Medicine : a Journal of the British Diabetic Association. 1995 January; 12(1): 30-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7712700

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Use of antihypertensive agents in patients with glucose intolerance. Author(s): McKenney JM, Goodman RP, Wright JT Jr. Source: Clin Pharm. 1985 November-December; 4(6): 649-56. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2866862

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Validation of capillary glucose measurements to detect glucose intolerance or type 2 diabetes mellitus in the general population. Author(s): Kruijshoop M, Feskens EJ, Blaak EE, de Bruin TW. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 2004 March; 341(1-2): 33-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14967156

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Vitamin and mineral deficiencies which may predispose to glucose intolerance of pregnancy. Author(s): Jovanovic-Peterson L, Peterson CM. Source: Journal of the American College of Nutrition. 1996 February; 15(1): 14-20. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8632110

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Waist to hip ratio, body mass index, and glucose intolerance from Funagata population-based diabetes survey in Japan. Author(s): Sekikawa A, Eguchi H, Igarashi K, Tominaga M, Abe T, Fukuyama H, Kato T. Source: The Tohoku Journal of Experimental Medicine. 1999 September; 189(1): 11-20. Erratum In: Tohoku J Exp Med 2000 April; 190(4): 295. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10622204

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Weight change amongst Nauruans over 6.5 years: extent, and association with glucose intolerance. Author(s): Sicree RA, Zimmet PZ, King H, Coventry JS. Source: Diabetes Research and Clinical Practice. 1987 November-December; 3(6): 327-36. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3665732

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Weight history, glucose intolerance, and insulin levels in middle-aged Swedish men. Author(s): Carlsson S, Persson PG, Alvarsson M, Efendic S, Norman A, Svanstrom L, Ostenson CG, Grill V. Source: American Journal of Epidemiology. 1998 September 15; 148(6): 539-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9753008

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Which cutoff level should be used in screening for glucose intolerance in pregnancy? Definition of Screening Methods for Gestational Diabetes Study Group of the Lombardy Section of the Italian Society of Diabetology. Author(s): Bonomo M, Gandini ML, Mastropasqua A, Begher C, Valentini U, Faden D, Morabito A. Source: American Journal of Obstetrics and Gynecology. 1998 July; 179(1): 179-85. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9704785

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CHAPTER 2. NUTRITION AND GLUCOSE INTOLERANCE Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and glucose intolerance.

Finding Nutrition Studies on Glucose Intolerance 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 “glucose intolerance” (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 glucose intolerance: •

Hypercholesterolemia in diabetes and glucose intolerance in the U.S. population. Author(s): National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892. Source: Harris, M I Diabetes-Care. 1991 May; 14(5): 366-74 0149-5992

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Inverse association between fish intake and risk of glucose intolerance in normoglycemic elderly men and women. Author(s): Department of Epidemiology, National Institute of Public Health and Environmental Protection, Bilthoven, Netherlands. Source: Feskens, E J Bowles, C H Kromhout, D Diabetes-Care. 1991 November; 14(11): 935-41 0149-5992

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Prevalence and determinants of glucose intolerance in a Dutch caucasian population. The Hoorn Study. Author(s): Institute for Research in Extramural Medicine, Vrije Universiteit, Amsterdam, the Netherlands. [email protected] Source: Mooy, J M Grootenhuis, P A de Vries, H Valkenburg, H A Bouter, L M Kostense, P J Heine, R J Diabetes-Care. 1995 September; 18(9): 1270-3 0149-5992

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Prevalence of glucose intolerance among Native Hawaiians in two rural communities. Native Hawaiian Health Research (NHHR) Project. Author(s): Pacific Biomedical Research Center, Manoa, Hawaii. [email protected] Source: Grandinetti, A Chang, H K Mau, M K Curb, J D Kinney, E K Sagum, R Arakaki, R F Diabetes-Care. 1998 April; 21(4): 549-54 0149-5992

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Subclinical states of glucose intolerance and risk of death in the U.S. Author(s): Department of Epidemiology, Johns Hopkins University School of Hygiene and Public Health, Baltimore, Maryland, USA. Source: Saydah, S H Loria, C M Eberhardt, M S Brancati, F L Diabetes-Care. 2001 March; 24(3): 447-53 0149-5992

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Ultrasonographic manifestations of carotid atherosclerosis and glucose intolerance in elderly eastern Finnish men. Author(s): Department of Epidemiology and Health Promotion, National Public Health Institute, Helsinki, Finland. [email protected] Source: Tuomilehto, J Qiao, Q Salonen, R Nissinen, A Salonen, J T Diabetes-Care. 1998 August; 21(8): 1349-52 0149-5992

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

Amitraz-induced glucose intolerance in rats: antagonism by yohimbine but not by prazosin. Author(s): Department of Veterinary Physiology and Pharmacology, Iowa State University, Ames 50011. Source: Smith, B E Hsu, W H Yang, P C Arch-Toxicol. 1990; 64(8): 680-3 0340-5761

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Betel nut (Areca catechu) consumption and the induction of glucose intolerance in adult CD1 mice and in their F1 and F2 offspring. Author(s): Cellular Mechanisms Research Group, London Hospital Medical College, UK.

Nutrition

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Source: Boucher, B J Ewen, S W Stowers, J M Diabetologia. 1994 January; 37(1): 49-55 0012-186X •

Glucose tolerance and insulin response to glucose load before and after enzyme inducing therapy in subjects with glucose intolerance and patients with NIDDM having hyperinsulinemia or relative insulin deficiency. Author(s): Department of Internal Medicine, University of Oulu, Finland. Source: Sotaniemi, E A Karvonen, I Diabetes-Res. 1989 July; 11(3): 131-9 0265-5985

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Glutamate decarboxylase (GAD65) and tyrosine phosphatase-like protein (IA-2) autoantibodies index in a regional population is related to glucose intolerance and body mass index. Author(s): Department of Family Medicine, Umea University, Sweden. Source: Rolandsson, O Hagg, E Hampe, C Sullivan, E P Nilsson, M Jansson, G Hallmans, G Lernmark, A Diabetologia. 1999 May; 42(5): 555-9 0012-186X

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Spontaneous glucose intolerance in the progeny of low dose streptozotocin-induced diabetic mice. Author(s): Medical Clinic III, Justus Liebig University, Giessen, Germany. Source: Linn, T Loewk, E Schneider, K Federlin, K Diabetologia. 1993 December; 36(12): 1245-51 0012-186X

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/

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Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: •

AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats

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

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

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

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

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

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

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

The following is a specific Web list relating to glucose intolerance; 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: •

Minerals Chromium Source: Healthnotes, Inc.; www.healthnotes.com

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CHAPTER 3. ALTERNATIVE MEDICINE AND GLUCOSE INTOLERANCE Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to glucose intolerance. At the conclusion of this chapter, we will provide additional sources.

National Center for Complementary and Alternative Medicine The National Center for Complementary and Alternative Medicine (NCCAM) of the National Institutes of Health (http://nccam.nih.gov/) has created a link to the National Library of Medicine’s databases to facilitate research for articles that specifically relate to glucose intolerance and complementary medicine. To search the database, go to the following Web site: http://www.nlm.nih.gov/nccam/camonpubmed.html. Select “CAM on PubMed.” Enter “glucose intolerance” (or synonyms) into the search box. Click “Go.” The following references provide information on particular aspects of complementary and alternative medicine that are related to glucose intolerance: •

A combined high-fiber, low-glycemic index diet normalizes glucose tolerance and reduces hyperglycemia and hyperinsulinemia in adults with hepatic cirrhosis. Author(s): Barkoukis H, Fiedler KM, Lerner E. Source: Journal of the American Dietetic Association. 2002 October; 102(10): 1503-7; Discussion 1507-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12396175

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A modified high-fat diet induces insulin resistance in rat skeletal muscle but not adipocytes. Author(s): Wilkes JJ, Bonen A, Bell RC. Source: The American Journal of Physiology. 1998 October; 275(4 Pt 1): E679-86. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9755088

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A study on Asian Indian and American vegetarians: indications of a racial predisposition to glucose intolerance. Author(s): Scholfield DJ, Behall KM, Bhathena SJ, Kelsay J, Reiser S, Revett KR. Source: The American Journal of Clinical Nutrition. 1987 December; 46(6): 955-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3318380

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Aberrant crypt focus promotion and glucose intolerance: correlation in the rat across diets differing in fat, n-3 fatty acids and energy. Author(s): Koohestani N, Chia MC, Pham NA, Tran TT, Minkin S, Wolever TM, Bruce WR. Source: Carcinogenesis. 1998 September; 19(9): 1679-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9771941

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Acute effect of low-calorie and low-carbohydrate diet on serum triiodothyronineresponse to glucose ingestion and its relation to glucose tolerance. Author(s): Koh H, Tsushima M, Waki M, Matsuyama T. Source: Hormone and Metabolic Research. Hormon- Und Stoffwechselforschung. Hormones Et Metabolisme. 1994 October; 26(10): 470-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7851870

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Adaptogenic activity of Siotone, a polyherbal formulation of Ayurvedic rasayanas. Author(s): Bhattacharya SK, Bhattacharya A, Chakrabarti A. Source: Indian J Exp Biol. 2000 February; 38(2): 119-28. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11218827

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Adaptogenic activity of Withania somnifera: an experimental study using a rat model of chronic stress. Author(s): Bhattacharya SK, Muruganandam AV. Source: Pharmacology, Biochemistry, and Behavior. 2003 June; 75(3): 547-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12895672

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Age-associated changes in the endocrine system. Author(s): Winger JM, Hornick T. Source: Nurs Clin North Am. 1996 December; 31(4): 827-44. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8969342

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Anti-diabetic effects of onion and garlic sulfoxide amino acids in rats. Author(s): Sheela CG, Kumud K, Augusti KT. Source: Planta Medica. 1995 August; 61(4): 356-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7480182

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Antihypertensive therapy in diabetic patients. Author(s): Weidmann P, Boehlen LM, de Courten M, Ferrari P.

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Source: Journal of Human Hypertension. 1992 December; 6 Suppl 2: S23-36. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1289510 •

Balanced intakes of natural triglycerides for optimum nutrition: an evolutionary and phytochemical perspective. Author(s): Broadhurst CL. Source: Medical Hypotheses. 1997 September; 49(3): 247-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9293470

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Beneficial effects of fish oil on glucose metabolism in spontaneously hypertensive rats. Author(s): Ajiro K, Sawamura M, Ikeda K, Nara Y, Nishimura M, Ishida H, Seino Y, Yamori Y. Source: Clinical and Experimental Pharmacology & Physiology. 2000 May-June; 27(5-6): 412-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10831245

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Betel nut (Areca catechu) consumption and the induction of glucose intolerance in adult CD1 mice and in their F1 and F2 offspring. Author(s): Boucher BJ, Ewen SW, Stowers JM. Source: Diabetologia. 1994 January; 37(1): 49-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8150230

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Carbohydrate intake and body mass index in relation to the risk of glucose intolerance in an elderly population. Author(s): Feskens EJ, Bowles CH, Kromhout D. Source: The American Journal of Clinical Nutrition. 1991 July; 54(1): 136-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2058574

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Chromium as a supplement. Author(s): Lukaski HC. Source: Annual Review of Nutrition. 1999; 19: 279-302. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10448525

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Chromium deficiency, glucose intolerance, and neuropathy reversed by chromium supplementation, in a patient receiving long-term total parenteral nutrition. Author(s): Jeejeebhoy KN, Chu RC, Marliss EB, Greenberg GR, Bruce-Robertson A. Source: The American Journal of Clinical Nutrition. 1977 April; 30(4): 531-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=192066

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Chromium, glucose intolerance and diabetes. Author(s): Anderson RA.

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Source: Journal of the American College of Nutrition. 1998 December; 17(6): 548-55. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9853533 •

Clinical features and metabolic derangements in acquired generalized lipodystrophy: case reports and review of the literature. Author(s): Misra A, Garg A. Source: Medicine; Analytical Reviews of General Medicine, Neurology, Psychiatry, Dermatology, and Pediatrics. 2003 March; 82(2): 129-46. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12640189

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Cystic fibrosis-related diabetes. Author(s): Mackie AD, Thornton SJ, Edenborough FP. Source: Diabetic Medicine : a Journal of the British Diabetic Association. 2003 June; 20(6): 425-36. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12786675

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Decreased carbohydrate intake is more important than increased fat intake in the glucose intolerance by a low-carbohydrate/high-fat diet. Author(s): Wang Y, Kaneko T, Wang PY, Sato A. Source: Diabetes Research and Clinical Practice. 2002 January; 55(1): 61-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11755480

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Diabetes is related to fatty acid imbalance in Eskimos. Author(s): Ebbesson SO, Kennish J, Ebbesson L, Go O, Yeh J. Source: Int J Circumpolar Health. 1999 April; 58(2): 108-19. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10429340

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Diabetes mellitus or an impaired glucose tolerance as a potential complicating factor in patients treated with high-dose therapy and autologous bone marrow transplantation. Author(s): Schouten HC, Maragos D, Vose J, Armitage JO. Source: Bone Marrow Transplantation. 1990 November; 6(5): 333-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2291995

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Diabetogenic impact of long-chain omega-3 fatty acids on pancreatic beta-cell function and the regulation of endogenous glucose production. Author(s): Holness MJ, Greenwood GK, Smith ND, Sugden MC. Source: Endocrinology. 2003 September; 144(9): 3958-68. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12933670

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Diet selection and metabolic fuels in three models of diabetes mellitus. Author(s): Bartness TJ, Rowland NE.

Alternative Medicine 101

Source: Physiology & Behavior. 1983 October; 31(4): 539-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6361816 •

Dietary chromium tripicolinate supplementation reduces glucose concentrations and improves glucose tolerance in normal-weight cats. Author(s): Appleton DJ, Rand JS, Sunvold GD, Priest J. Source: Journal of Feline Medicine and Surgery. 2002 March; 4(1): 13-25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11869052

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Dietary factors in the aetiology of diabetes. Author(s): Virtanen SM, Aro A. Source: Annals of Medicine. 1994 December; 26(6): 469-78. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7695875

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Dietary fish oil normalize dyslipidemia and glucose intolerance with unchanged insulin levels in rats fed a high sucrose diet. Author(s): Lombardo YB, Chicco A, D'Alessandro ME, Martinelli M, Soria A, Gutman R. Source: Biochimica Et Biophysica Acta. 1996 January 19; 1299(2): 175-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8555262

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Dietary fructose in the management of intractable diarrhea of infancy. Author(s): Clark JH, Bullock L, Fitzgerald JF. Source: Journal of Pediatric Gastroenterology and Nutrition. 1986 January; 5(1): 81-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3080579

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Differential effects of honey, sucrose, and fructose on blood sugar levels. Author(s): Shambaugh P, Worthington V, Herbert JH. Source: Journal of Manipulative and Physiological Therapeutics. 1990 July-August; 13(6): 322-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2394949

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Distinct role of adiposity and insulin resistance in glucose intolerance: studies in ventromedial hypothalamic-lesioned obese rats. Author(s): Kageyama A, Hirano T, Kageyama H, Osaka T, Namba Y, Tsuji M, Adachi M, Inoue S. Source: Metabolism: Clinical and Experimental. 2002 June; 51(6): 716-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12037724

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Does a high-carbohydrate diet have different effects in NIDDM patients treated with diet alone or hypoglycemic drugs? Author(s): Parillo M, Giacco R, Ciardullo AV, Rivellese AA, Riccardi G.

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Source: Diabetes Care. 1996 May; 19(5): 498-500. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8732716 •

Does dietary fat influence insulin action? Author(s): Storlien LH, Kriketos AD, Jenkins AB, Baur LA, Pan DA, Tapsell LC, Calvert GD. Source: Annals of the New York Academy of Sciences. 1997 September 20; 827: 287-301. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9329762

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Effect of dietary fish oil on 2-deoxy-D-3H glucose uptake in isolated adipocytes of rats fed various diets. Author(s): Macho L, Fickova M, Sebokova E, Mitkova A, Klimes I. Source: Annals of the New York Academy of Sciences. 1993 June 14; 683: 237-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8352445

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Effect of eicosapentaenoic acid ethyl ester v. oleic acid-rich safflower oil on insulin resistance in type 2 diabetic model rats with hypertriacylglycerolaemia. Author(s): Minami A, Ishimura N, Sakamoto S, Takishita E, Mawatari K, Okada K, Nakaya Y. Source: The British Journal of Nutrition. 2002 February; 87(2): 157-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11895168

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Effect of ovariectomy on adipose tissue of mice in the absence of estrogen receptor alpha (ERalpha): a potential role for estrogen receptor beta (ERbeta). Author(s): Naaz A, Zakroczymski M, Heine P, Taylor J, Saunders P, Lubahn D, Cooke PS. Source: Hormone and Metabolic Research. Hormon- Und Stoffwechselforschung. Hormones Et Metabolisme. 2002 November-December; 34(11-12): 758-63. Erratum In: Horm Metab Res. 2003 April; 35(4): 271. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12660895

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Effect of pinitol treatment on insulin action in subjects with insulin resistance. Author(s): Davis A, Christiansen M, Horowitz JF, Klein S, Hellerstein MK, Ostlund RE Jr. Source: Diabetes Care. 2000 July; 23(7): 1000-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10895854

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Effect of poly herbal formulation, EuMil, on chronic stress-induced homeostatic perturbations in rats. Author(s): Muruganandam AV, Kumar V, Bhattacharya SK.

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Source: Indian J Exp Biol. 2002 October; 40(10): 1151-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12693696 •

Effects of chromium picolinate supplementation on insulin sensitivity, serum lipids, and body weight in dexamethasone-treated rats. Author(s): Kim DS, Kim TW, Park IK, Kang JS, Om AS. Source: Metabolism: Clinical and Experimental. 2002 May; 51(5): 589-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11979390

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Effects of cisplatin and taxol on inducible nitric oxide synthase, gastrin and somatostatin in gastrointestinal toxicity. Author(s): Wang Y, Aggarwal SK. Source: Anti-Cancer Drugs. 1997 October; 8(9): 853-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9402312

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One-year treatment with ethyl esters of n-3 fatty acids in patients with hypertriglyceridemia and glucose intolerance: reduced triglyceridemia, total cholesterol and increased HDL-C without glycemic alterations. Author(s): Sirtori CR, Crepaldi G, Manzato E, Mancini M, Rivellese A, Paoletti R, Pazzucconi F, Pamparana F, Stragliotto E. Source: Atherosclerosis. 1998 April; 137(2): 419-27. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9622285

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Plasma catecholamines, dietary carbohydrate, and glucose intolerance: a comparison between young and old men. Author(s): Chen M, Halter JB, Porte D Jr. Source: The Journal of Clinical Endocrinology and Metabolism. 1986 June; 62(6): 1193-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3700584

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Role of 5-hydroxytryptamine (serotonin) in oral glucose intolerance. Author(s): Narvanen S. Source: Scand J Clin Lab Invest Suppl. 1983; 167: 1-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6581528

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Short-term treatment of glucose intolerance in middle-aged subjects by diet, exercise and sulfonylurea. Author(s): Cederholm J. Source: Upsala Journal of Medical Sciences. 1985; 90(3): 229-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4095819

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Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: •

Alternative Medicine Foundation, Inc.: http://www.herbmed.org/

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AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats

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Chinese Medicine: http://www.newcenturynutrition.com/

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drkoop.com: http://www.drkoop.com/InteractiveMedicine/IndexC.html

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

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

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

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MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine

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

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HealthGate: http://www.tnp.com/

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

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

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

The following is a specific Web list relating to glucose intolerance; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •

General Overview Cardiovascular Disease Overview Source: Healthnotes, Inc.; www.healthnotes.com Diabetes Source: Healthnotes, Inc.; www.healthnotes.com Insulin Resistance Syndrome Source: Healthnotes, Inc.; www.healthnotes.com Obesity Source: Integrative Medicine Communications; www.drkoop.com

General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the

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MEDLINEplus site at http://www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources.

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CHAPTER 4. PATENTS ON GLUCOSE INTOLERANCE Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.8 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “glucose intolerance” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on glucose intolerance, we have not necessarily excluded non-medical patents in this bibliography.

Patents on Glucose Intolerance By performing a patent search focusing on glucose intolerance, 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. 8Adapted

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

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

Liquid nutritional formula for glucose intolerance Inventor(s): Besozzi; Elizabeth M. (Columbus, OH), Cashmere; Karen A. (Columbus, OH) Assignee(s): Abbott Laboratories (Abbott Park, IL) Patent Number: 4,921,877 Date filed: December 16, 1987 Abstract: An improved nutritionally complete formula containing a unique fibercontaining carbohydrate blend, at a relatively low concentration; a unique fat blend, at a relatively high concentration; protein; carnitine; myoinositol; vitamins and minerals, including chromium. This formula is for the dietary management of patients with glucose intolerance. Excerpt(s): The invention relates to improved enteral nutritional formulas and more particularly to formulas which provide protein, low carbohydrate, high fat, dietary fiber and micronutrients specific to the needs of glucose intolerant individuals. Primary treatment for glucose intolerance is strict adherence to a diet which minimizes postprandial glucose response, and in many cases, use of medications (insulin or oral hypoglycemic agents). The American Diabetes Association (ADA) currently recommends a diet in which protein accounts for 12-20% total calories (kcal), carbohydrate for 50-60% kcal, and fat for the remaining kcal (about 30%). Diabetes Care 2:250-253, 1979. The ADA also recommends consumption of complex carbohydrates that are high in dietary fiber (40 g/day for men, 25 g/day for women), and consumption of fats that are low in cholesterol (<300 mg/day) and low in saturated fatty acids (polyunsaturated fatty acids : saturated fatty acids or P:S ratio=1 or greater), Diabetes Outlook 21:1-8, 1986. Most currently available liquid enteral formulas comply, for the most part, with the ADA recommendations. One such enteral formula sold by Fresenius Diatetik, Bad Homburg, West Germany under the name Diabetiker-Flussignahrung, contains 43% kcal as carbohydrate, 37% as fat and 20% kcal as protein. Enteral formulas commonly used in patients with glucose intolerance in the United States include Compleat.RTM. nutritional formula (Sandoz Nutrition, Minneapolis, Minn.), which contains 16% kcal as protein, 48% kcal as carbohydrate, 36% kcal from fat, and dietary fiber from fruits and vegetables, Enrich.RTM. nutritional formula (Ross Laboratories, Columbus, Ohio), which contains 14.5% kcal as protein, 55% kcal as carbohydrate, 30.5% kcal as fat, and dietary fiber from soy polysaccharide and Osmolite.RTM. nutritional formula (Ross Laboratories, Columbus, Ohio) which contains 14.0% kcal as protein, 54.6% kcal as carbohydrate and 31.4% kcal as fat. Web site: http://www.delphion.com/details?pn=US04921877__

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Use of diazoxide for the treatment of metabolic syndrome and diabetes complications Inventor(s): Morad; Latifa (Haifa, IL), Vardi; Pnina (Haifa, IL) Assignee(s): none reported Patent Number: 6,197,765 Date filed: June 8, 1999

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Abstract: The present invention discloses a treatment for syndrome-X, and resulting complications, that include hyperlipidemia, hypertension, central obesity, hyperinsulinemia and impaired glucose intolerance. Diabetic complications include excess proinsulin levels. Excerpt(s): The present invention relates to a novel treatment for metabolic syndrome and resulting complications, such as obesity, hypertension, hyperlipidemia, hyperinsulinemia and impaired glucose tolerance. In addition, it concerns the use of diazoxide for the treatment of syndrome-X and resulting complications, as well as diabetic complications. Oral diazoxide (7-chloro-3-methyl-2H-1,2,4-benzothiadiazine 1,1-diazoxide) is a nondiuretic congener of the thiazide diuretics which inhibits insulin release from the pancreas (ref. 1). Diazoxide was originally developed for the treatment of hypertension. One of the adverse affects of diazoxide was found to be hyperglycemia, which proved useful in the treatment of hypoglycemia. The hyperglycemia caused by diazoxide is usually transitory and is due to decreased insulin secretion and decreased peripheral utilization of glucose (ref. 2). Diazoxide is now used primarily for the treatment of hypoglycemia due to hyperinsulinism, associated with conditions such as inoperable islet cell adenoma or carcinoma (ref. 3). The drug is currently marketed in the U.S. under the tradename Proglycem. Syndrome-X is a metabolic syndrome. The term syndrome-X was given by Reaven et al describing a condition characterized by central obesity, and metabolic manifestations including resistance to insulin stimulated glucose uptake, hyperinsulinemia, glucose intolerance (not necessarily diabetes), increased level of very low density lipoprotein triglyceride (VLDL), decreased level of high density lipoprotein cholesterol (HDL) concentrations and hypertension (refs. 4, 5). Each of these characteristic features are considered to be risk factors for development of atherosclerosis and other `old age` diseases. It is believed that syndrome-X is caused by insulin resistance, but no treatment is available at present. Web site: http://www.delphion.com/details?pn=US06197765__ •

Use of thiazolidinedione derivatives and related antihyperglycemic agents in the treatment of impaired glucose tolerance in order to prevent or delay the onset of noninsulin-dependent diabetes mellitus Inventor(s): Antonucci; Tammy (Mequon, WI), Lockwood; Dean (Ann Arbor, MI), Norris; Rebecca (Kewadin, MI), Olefsky; Jerrold (Solano Beach, CA) Assignee(s): Sankyo Company, Limited (Tokyo, JP) Patent Number: 5,478,852 Date filed: August 23, 1994 Abstract: Novel methods of using thiazolidinone derivatives and related antihyperglycemic agents to treat populations experiencing impaired glucose intolerance in order to prevent or delay the onset of noninsulin-dependent diabetes mellitus (NIDDM) and complications arising therefrom are disclosed. Excerpt(s): The present invention pertains to a number of compounds which can be used to treat impaired glucose tolerance in order to prevent or delay the onset of noninsulindependent diabetes mellitus (NIDDM). More specifically, the present invention involves in one embodiment administering to a patient certain known thiazolidinedione derivatives and related antihyperglycemic agents which reduce fasting insulin levels and return normal glucose tolerance to an individual, thus preventing or delaying the onset of NIDDM or complications resulting therefrom. Diabetes is one of the most

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prevalent chronic disorders worldwide with significant personal and financial costs for patients and their families, as well as for society. Different types of diabetes exist with distinct etiologies and pathogeneses. For example, diabetes mellitus is a disorder of carbohydrate metabolism, characterized by hyperglycemia and glycosuria and resulting from inadequate production or utilization of insulin. Diabetes mellitus often develops from certain at risk populations, one such population is individuals with impaired glucose tolerance (IGT). Impaired glucose tolerance is a condition intermediate between frank, noninsulin-dependent diabetes mellitus and normal glucose tolerance in which the affected person's postprandial glucose response is abnormal as assessed by 2-hour postprandial plasma glucose levels. This IGT population progresses to a certain form of diabetes mellitus, specifically noninsulin-dependent diabetes mellitus (NIDDM). Web site: http://www.delphion.com/details?pn=US05478852__

Patent Applications on Glucose Intolerance As of December 2000, U.S. patent applications are open to public viewing.9 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to glucose intolerance: •

Cyclic a-amino-y hydroxyamide compounds Inventor(s): Boulanger, Michelle; (Chatou, FR), Fourquez, Jean-Marie; (Suresnes, FR), Hussson-Robert, Bernadette; (Nanterre, FR), Levens, Nigel; (Vaucresson, FR), Nosjean, Olivier; (Rueil Malmaison, FR), Wierzbicki, Michel; (L'Etang La Ville, FR) Correspondence: The Firm OF Hueschen And Sage; 500 Columbia Plaza; 350 East Michigan Avenue; Kalamazoo; MI; 49007; US Patent Application Number: 20030004138 Date filed: June 18, 2002 Abstract: Compound of formula (I): 1wherein: 2represents an optionally substituted saturated carbon ring having from 4 to 8 ring members,R.sub.1 and R.sub.4, which may be identical or different, each represents hydrogen or acyl,R.sub.2 and R.sub.3, which may be identical or different, each represents hydrogen or alkyl,R.sub.5 and R.sub.6, which may be identical or different, each represents hydrogen or alkyl, or R.sub.5 and R.sub.6 together, with the nitrogen atom carrying them, form an optionally substituted nitrogen-containing heterocycle,stereoisomers thereof, and also addition salts thereof with a pharmaceutically acceptable acid.Medicinal products containing the same which are useful for treatment of glucose intolerance or of disorders associated with hyperglycemia. Excerpt(s): A cyclic.alpha.-amino-.gamma.-hydroxy acid compound has been described in the journal J. Org. Chem. 1994, 59 (26), 8101-6, without their having been any pharmacological activity mentioned for that compound. In addition to the fact that they are new, the compounds of the present invention have valuable pharmacological properties. They have blood glucose-lowering properties, rendering them beneficial in the treatment of glucose intolerance and disorders associated with hyperglycaemia,

9

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

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such as type II diabetes or obesity. to stereoisomers thereof, and also to addition salts thereof with a pharmaceutically acceptable acid. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Novel compounds and therapeutic uses thereof Inventor(s): Sankaranarayanan, Alangudi; (Ahmedabad, IN) Correspondence: Sughrue Mion, Pllc; 2100 Pennsylvania Avenue, N.W.; Washington; DC; 20037; US Patent Application Number: 20030225102 Date filed: April 8, 2003 Abstract: The invention discloses a novel series of compound represented by general formula (I), 1its derivatives, analogs, tautomeric forms, stereoisomers, polymorphs, pharmaceutically acceptable salts, solvates wherein X, n, k, z, R1, R2, R3, R4, R5 and R6 are as defined in the specification that are useful in (i) normalizing elevated blood glucose levels in diabetes, (ii) treating disorders related to glucose intolerance and (iii) for scavenging free radicals of mammals.The invention also discloses pharmaceutically acceptable composition comprising these compounds, method for preparation of the compounds as defined above and method of treating mammals including human beings by administering an effective amount of said compounds to a subject in need thereof. The invention further discloses use of these compounds in the manufacture of a medicament useful for treatment of different disease conditions as stated above. Excerpt(s): This application claims benefit from U.S. provisional application No. 60/370,224 filed Apr. 08, 2002 which is incorporated herein by reference in its entirety. The present invention relates to novel heterocyclic compounds useful for normalizing elevated blood glucose levels in diabetics and in treating disorders related to glucose intolerance. These compounds inhibit the enzyme DPP-IV, that degrade the peptide GLP-1, providing for enhanced levels of active GLP-1, a peptide which normalizes elevated blood glucose levels. 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 glucose intolerance, 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 “glucose intolerance” (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 glucose intolerance. You can also use this procedure to view pending patent applications concerning glucose intolerance. 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 5. BOOKS ON GLUCOSE INTOLERANCE Overview This chapter provides bibliographic book references relating to glucose intolerance. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on glucose intolerance 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 “glucose intolerance” (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 glucose intolerance: •

Diabetes Mellitus in the Elderly: A Practical Guide Source: New York, NY: Raven Press. 1990. 276 p. Contact: Available from Raven Press. 1185 Avenue of the Americas, Dept. 5B, New York, NY 10036. (800) 777-2836 or (212) 930-9500. Fax (212) 869-3495. PRICE: $80.50 plus shipping (as of 1995). ISBN: 0881676241. Summary: This book consists of a series of state-of-the-art essays discussing practical aspects of diabetes mellitus as it relates to the elderly. Eighteen chapters cover topics including: the impact of diabetes on an aging society; glucose intolerance versus diabetes mellitus; glycemic control and diabetic complications; diet therapy; the role of exercise; pharmacological therapy; dermatological disorders; foot care and foot problems; diabetic retinopathy and eye disorders; diabetic renal disease; diabetic neuropathy; atherosclerotic, cardiovascular and cerebrovascular disease; hypoglycemia;

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glucose monitoring; hyperosmolar nonketotic coma; education and counseling for diabetes self-care; and diabetes mellitus and its relationship to other age-prevalent illnesses. Numerous tables, flowsheets, and diagrams are used to simplify the material presented and to provide ready reference. A section of handouts is also provided for patient education purposes. A subject index is included. 165 references. •

Medical Management of Type 2 Diabetes. 4th ed Source: Alexandria, VA: American Diabetes Association. 1998. 154 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: $31.95 for members; $39.95 for nonmembers; plus shipping and handling. ISBN: 0945448937. Order number 540401. Summary: This book, which is part of the American Diabetes Association's Clinical Education Series, provides health professionals with the information they need to give the best possible medical care to patients who have diabetes. The book offers an overview of type 2 diabetes, plus state of the art instruction in all areas affecting patients who have the disease. The book begins with a section on diagnosis and classification. Topics include types of diabetes mellitus and other categories of glucose intolerance, indications for screening, diagnostic criteria, oral glucose tolerance testing, criteria for diagnosis of gestational diabetes mellitus, and evaluation and classification of patients before treatment. The next section discusses the pathogenesis of type 2 diabetes, focusing on insulin secretion, insulin resistance, and pathogenic sequences. This is followed by a section on the management of type 2 diabetes through nutrition, exercise, and pharmacologic intervention with insulin and oral agents. Other topics include special therapeutic problems and assessment of treatment efficacy. The fourth section addresses behavior change: desirable behaviors in type 2 diabetes, factors influencing behaviors, and components of the behavior change process. This process involves assessment, planning, implementation, documentation, and evaluation. The final section is devoted to detecting and treating complications, including accelerated macrovascular disease, diabetic retinopathy, diabetic renal disease, diabetic foot problems, neuropathic conditions, metabolic problems, and infection. Included are several case studies. The book concludes with an index. 2 figures. 32 tables. Numerous references.

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Diabetes in Pictures: The Epidemiology and Primary Prevention of Non-Insulin Dependent Diabetes Mellitus Source: Frankfurt am Main, Germany: Hoechst. 1993. 43 p. Contact: Available from Hoechst Aktiengesellschaft. D-65926 Frankfurt am Main, Germany. PRICE: Single copy free. Summary: This booklet presents an overview of the epidemiology and primary prevention of noninsulin-dependent diabetes mellitus (NIDDM). The introductory section covers the worldwide incidence and prevalence of diabetes; the classification of diabetes mellitus and other categories of glucose intolerance; the public health perspectives of NIDDM; risk factors for NIDDM, including 'Westernization' of diet; and prevalence in different ethnic groups and geographic locations. Topics include the natural history of NIDDM; the role of the 'thrifty genotype' concept and the genetic basis of NIDDM; environmental determinants of NIDDM; the epidemiological contribution to understanding the pathogenesis of NIDDM; the heterogeneity of NIDDM; implications for the prevention of NIDDM, hyperinsulinemia, and cardiovascular disease; the primary prevention of NIDDM; and high risk individuals and populations. The

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monograph features full-color charts and graphs illustrating the topics. 33 figures. 32 references.

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

Classification Source: in Edelman, S.V. and Henry, R.R. Diagnosis and Management of Type 2 Diabetes. Caddo, OK: Professional Communications, Inc. 2002. p. 29-37. Contact: Available from Professional Communications, Inc., Fulfillment Center, PO Box 10, Caddo, OK 74729-0010. (800)337-9838. Fax (580)367-9989. E-mail: [email protected]. ISBN: 1884735754. PRICE: $21.95, plus shipping and handling. Summary: Diabetes mellitus and other categories of glucose intolerance can be divided into three main clinical categories: diabetes mellitus (with four clinical subclasses), impaired glucose tolerance (IGT), and gestational diabetes mellitus (GDM). This chapter on classification of diabetes is from a handbook for primary care providers that offers a concise overview of the diagnosis and management of type 2 diabetes. The authors define and discuss five subclasses of diabetes: type 1 diabetes mellitus, type 2 diabetes mellitus, GDM, malnutrition-related diabetes mellitus, and other types of diabetes associated with certain conditions. A final section considers some of the problems with classification, including exceptions to the standard categories. 2 tables. 3 references.

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Exercise Source: in Edelman, S.V. and Henry, R.R. Diagnosis and Management of Type 2 Diabetes. Caddo, OK: Professional Communications, Inc. 2002. p. 65-68. Contact: Available from Professional Communications, Inc., Fulfillment Center, PO Box 10, Caddo, OK 74729-0010. (800)337-9838. Fax (580)367-9989. E-mail: [email protected]. ISBN: 1884735754. PRICE: $21.95, plus shipping and handling. Summary: Many adults with diabetes are sedentary and obese, which can contribute to the development of glucose intolerance. Therefore, physical activity should be included as an essential treatment component in the diabetes management plan unless contraindicated in a given individual. This chapter on exercise is from a handbook for primary care providers that offers a concise overview of the diagnosis and management of type 2 diabetes. The authors describe the benefits of exercise, precautions and considerations, and a recommended exercise prescription. 2 tables. 2 references.

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New Therapies for Non-Insulin-Dependent Diabetes Mellitus: Thiazolidinediones Source: in LeRoith, D.; Taylor, S.I.; Olefsky, J.M., eds. Diabetes Mellitus: A Fundamental and Clinical Text. Philadelphia, PA: Lippincott-Raven Publishers. 1996. p. 661-668. Contact: Available from Lippincott-Raven Publishers. 12107 Insurance Way, Hagerstown, MD 21740-5184. (800) 777-2295. Fax (301) 824-7390. PRICE: $199.00. ISBN: 0397514565. Summary: The treatment of noninsulin-dependent diabetes mellitus (NIDDM) has involved the use of insulin or insulin secretagogues such as sulfonylureas or biguanides such as metformin. Although these agents have been effective to a degree, they do not deal directly with the underlying pathology of insulin resistance. This chapter, from a medical textbook on diabetes, describes the use of the thiazolidinediones, a class of drugs that may directly decrease insulin resistance by enhancing insulin action in skeletal muscle, liver, and adipose (fat) tissue. One of these compounds, troglitazone, has progressed to late-stage clinical development. The authors cover how thiazolidinediones improve insulin sensitivity in animal models of diabetes, how these drugs may improve the insulin resistance syndrome, the use of troglitazone in NIDDM, the use of troglitazone in impaired glucose tolerance (IGT), and the potential use of troglitazone in polycystic ovarian syndrome. The authors conclude that persons with other insulin-resistant states such as steroid-induced glucose intolerance and severe insulin resistance, as well as women with a history of gestational diabetes, are also populations in whom insulin-sensitizing agents would be valuable, both in treating and potentially preventing hyperglycemic states. 6 figures. 49 references.

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Carbohydrate Metabolism in Renal Failure Source: in Kopple, J.D. and Massry, S.G. Nutritional Management of Renal Disease. Baltimore, MD: Williams and Wilkins. 1997. p. 63-76. Contact: Available from Williams and Wilkins. 351 West Camden Street, Baltimore, MD 21201-2436. (800) 638-0672 or (410) 528-4223. Fax (800) 447-8438 or (410) 528-8550. PRICE: $99.00. ISBN: 068304740X. Summary: This chapter on carbohydrate metabolism is from a medical textbook on nutrition and metabolism of individuals with renal disease or renal failure. The authors note that many aspects of carbohydrate metabolism are impaired in patients with chronic renal failure (CRF). These derangements lead to glucose intolerance in these patients. The two major defects that underlie glucose intolerance in uremia are resistance to the peripheral action of insulin and impaired insulin secretion. When these two abnormalities are present in a particular patient, glucose intolerance ensues. Despite impaired insulin secretion, the increase in the blood levels of insulin in response to hyperglycemia may be decreased, normal, or increased. These variations are most likely due to differences in the degree of the impairment in insulin secretion or its metabolic clearance rate. The authors caution that these disturbances and the secondary hyperparathyroidism may all contribute to the increased risk for atherogenesis in patients with CRF. Postprandial (after meals) hyperglycemia in the glucose intolerant uremic patient may, by itself, be a risk factor for atherosclerotic cardiovascular disease. In addition, hyperinsulinemia and insulin resistant state may be associated with hypertension, which is an important risk factor for cardiac disease in uremia. 2 figures. 1 table. 88 references. (AA-M).

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Nutritional and Metabolic Liver Diseases Source: in Sherlock, S.; Dooley, J. Diseases of the Liver and Biliary System. Malden, MA: Blackwell Science, Inc. 2002. p.423-452. Contact: Available from Blackwell Science, Inc. 350 Main Street, Commerce Place, Malden, MA 02148. (800) 215-1000 or (617) 388-8250. Fax (617) 388-8270. E-mail: [email protected]. Website: www.blackwell-science.com. PRICE: $178.95. ISBN: 0632055820. Summary: This chapter on nutritional and metabolic liver diseases is from a textbook that presents a comprehensive and up-to-date account of diseases of the liver and biliary system. The chapter covers malnutrition; fatty liver, including diagnosis and classification; non-alcoholic fatty liver disease, including hepatic steatosis, steatonecrosis, the effects of the jejuno-ileal bypass, parenteral nutrition, and vitamins; carbohydrate metabolism in liver disease, including hypoglycemia and hyperglycemia; the liver in diabetes mellitus, including insulin and the liver, hepatic histology, clinical features, and liver function tests; hepatobiliary disease and diabetes, including the glucose intolerance of cirrhosis and the treatment of diabetes in patients with cirrhosis; glycogen storage disease (types I through VI) and hepatic glycogen synthetase deficiency; hereditary fructose intolerance; glutaric aciduria type II, galactosemia; mucopolysaccharidoses; familial hypercholesterolemia; amyloidosis; alpha1-antitrypsin deficiency; hereditary tyrosinemia; cystic fibrosis; liver and thyroid, including thyrotoxicosis, myxoedema, and changes with hepatocellular disease; liver and adrenal; liver and growth hormone; hepatic porphyrias, including acute intermittent porphyria, hereditary coproporphyria, variegate porphyria, porphyria cutanea tarda, erythropoietic protoporphyria, hepato-erythropoietic porphyria, and secondary coproporphyrias; hereditary hemorrhagic teleangiectasia; and dystrophic myotonica. Each section includes its own list of references for further reading. 19 figures. 6 tables. 184 references.

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Prevalence and Incidence of Non-Insulin-Dependent Diabetes Source: in Harris, M.I., et al., eds., for the National Diabetes Data Group (NDDG). Diabetes in America. 2nd ed. Bethesda, MD: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health. 1995. p. 47-67. Contact: Available from National Diabetes Information Clearinghouse (NDIC). 1 Information Way, Bethesda, MD 20892-3560. (800) 860-8747 or (301) 654-3327. Fax (301) 634-0716. E-mail: [email protected]. Also available at http://www.niddk.nih.gov/. PRICE: Full-text book and chapter available online at no charge; book may be purchased for $20.00. Order number: DM-96 (book). Summary: This chapter on the prevalence and incidence of noninsulin dependent diabetes (NIDDM, or Type II) is from a compilation and assessment of data on diabetes and its complications in the United States. In 1993, approximately 7.8 million people in the United States had been diagnosed as having diabetes. This represents a prevalence rate of 3.1 percent of the U.S. population. However, rates range from about 1.3 percent of those age 18 to 44 years to about 10.4 percent of those older than 65 years. Both the prevalence rate for diabetes and the number of people with diabetes have increased steadily since a national system for ascertaining diagnosed diabetes was established in 1958. Diabetes is more prevalent in U.S. blacks, Mexican Americans, and Native Americans, compared with non-Hispanic whites. For all ages, approximately 90 percent of people with diabetes have NIDDM, but at age greater than 45 years virtually all people with diabetes have NIDDM. In addition to known cases of NIDDM, there is about one undiagnosed case of NIDDM for every diagnosed case, based on oral glucose

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tolerance testing in U.S. population samples. About 11 percent of U.S. adults had impaired glucose tolerance (IGT) in national surveys. Rates of total glucose intolerance (diabetes plus IGT) range from 7 to 14 percent at age 20 to 44 years to 28 to 44 percent at age 45 to 74 years, depending on the racial or ethnic group studied. The authors note that monitoring of national trends in the prevalence and incidence of NIDDM is needed so that the burden of diabetes can be assessed, the impact of risk factors can be described, interventions can be developed and their impacts determined, and needs for future health services can be projected. 7 appendices. 12 figures. 6 tables. 73 references. (AA-M). •

Trace Element Metabolism in Renal Disease and Renal Failure Source: in Kopple, J.D. and Massry, S.G. Nutritional Management of Renal Disease. Baltimore, MD: Williams and Wilkins. 1997. p. 395-414. Contact: Available from Williams and Wilkins. 351 West Camden Street, Baltimore, MD 21201-2436. (800) 638-0672 or (410) 528-4223. Fax (800) 447-8438 or (410) 528-8550. PRICE: $99.00. ISBN: 068304740X. Summary: This chapter on trace element metabolism is from a medical textbook on nutrition and metabolism of individuals with renal disease or renal failure. It is generally accepted that the term 'trace element' applies to elements that occur in the body at concentrations of less than 50 mg per kg under normal conditions. The definition of 'essential' trace elements is that the element should be present in healthy tissues; deficiency of the element consistently produces functional impairment; the abnormalities induced by the deficiency are always followed by specific biochemical changes; and addition of the element prevents or corrects these changes. Topics include methodology for the measurement of trace elements; trace element concentrations in uremia; the potential contribution of trace elements to the uremic syndrome, including impairment of renal function, susceptibility to cancer, cardiovascular disease, glucose intolerance, bone disease, anemia, enzyme dysfunction, encephalopathy and coma, and immune deficiency; factors affecting trace element concentration, including inadequate intake, decreased availability, impaired reabsorption, excessive excretion, and extracorporeal losses; specific examples relating to aluminum, lead, selenium and arsenic, zinc, vanadium, silicon, and chromium; and therapeutic considerations. The authors caution that the treatment of uremia by dialysis strategies may cause changes in trace element handling. Trace elements should be considered in the case of any unexplained toxic event in uremia. 5 tables. 89 references. (AA-M).

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Diabetes and Insulin Action Source: in Kuh, D.; Ben-Shlomo, Y. A Life Course Approach to Chronic Disease Epidemiology. Cary, NY: Oxford University Press. 1997. p. 78-100. Contact: Available from Oxford University Press. 2001 Evans Road, Cary, NY 27513. (800) 451-7556. PRICE: $65.00. ISBN: 0192627821. Summary: This chapter reviews the evidence that the risk of type 2 diabetes in adult life may be established by nutrition and growth in fetal life. Five studies have examined the relation of size at birth to impaired glucose tolerance or type 2 diabetes in later life. Two studies in England found a strong inverse association between birthweight and the prevalence of glucose intolerance in later life. The association of reduced size at birth with type 2 diabetes has also been confirmed in three other populations; however, the relationship was less strong than in the original English populations and the form of the relationship was nonlinear. Other studies in children and young adults show that

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plasma glucose levels after oral glucose challenge are inversely related to birthweight. Recent studies suggest that glucose intolerance is related more strongly to thinness at birth, measured by low ponderal index, than to low birthweight. Suggestions that the association can be accounted for by selective survival of low birthweight infants genetically predisposed to diabetes are not compatible with historical data on infant mortality rates. The association between size at birth and diabetes could be mediated through impairment of insulin secretion, resistance to the action of insulin in lowering blood glucose levels, or both. The association of thinness at birth with insulin resistance and glucose intolerance in adult life could also have a genetic or an environmental explanation. The article highlights research on these mediating influences. It concludes that, whatever the mechanism of the association between thinness at birth and risk of type 2 diabetes later in life, control of obesity is likely to be effective in reducing the risk of diabetes in individuals who were thin at birth. 3 figures. 3 tables. 72 references. (AAM). •

Genetic Counseling and Family Planning Source: in Reece, E.A. and Coustan, D.R., eds. Diabetes Mellitus in Pregnancy. 2nd ed. New York, NY: Churchill Livingstone. 1995. p. 399-415. Contact: Available from Churchill Livingstone. 300 Lighting Way, Secaucus, NJ 07094. (800) 553-5426. PRICE: $92.00. ISBN: 0443089795. Summary: This chapter reviews what is known regarding the various genetic factors that predispose an individual to glucose intolerance. The authors note that although great progress has been achieved in unraveling the genetic basis of diabetes, the exact mechanisms of inheritance remain unclear. Topics include HLA and disease susceptibility; the classification of glucose intolerance; HLA association with IDDM; HLA susceptibility and beta-cell destruction in IDDM; Non-HLA associations with IDDM; genetic counseling for IDDM, NIDDM, and gestational diabetes; and family planning considerations including prepregnancy planning, maternal complications, and contraceptive choices. 4 figures. 9 tables. 110 references. (AA-M).

•

Enteral Feeding: Methods of Delivery, Formula Selection, and Complications Source: in Kirby, D.F. and Dudrick, S.J., eds. Practical Handbook of Nutrition in Clinical Practice. Boca Raton, FL: CRC Press. 1994. p. 119-133. Contact: Available from CRC Press. 2000 Corporate Boulevard NW., Boca Raton, FL 33431. (800) 272-7737 or (561) 994-0555. Fax (800) 374-3401. E-mail: [email protected]. Website: http://www.crcpress.com. PRICE: $89.95. ISBN: 0849378478. Summary: This chapter, from a clinical nutrition textbook, discusses enteral feeding, specifically methods of delivery, formula selection, and complications. Formulas include blended diets and formulas, lactose-containing versus lactose-free, high nitrogen, elemental, specialty (pulmonary, renal failure, hepatic failure, trauma, postoperative, glucose intolerance, fiber-containing, and medium-chain triglyceride), modular diets, and supplements. Complications include mechanical, medication delivery, metabolic complications, and gastrointestinal complications, including aspiration, diarrhea, and constipation. The authors conclude that enteral nutrition is a safe and effective modality for feeding most patients who require nutritional support, including patients with disease of the gastrointestinal tract itself. Recent trends have seen a movement away from parenteral nutrition to enteral nutrition, often in patients who previously were thought not to be candidates for enteral support. 1 table. 83 references. (AA-M).

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Nutrition Care in Diabetes Mellitus and Reactive Hypoglycemia Source: in Mahan, L.K. and Escott-Stump, S. Krause's Food, Nutrition, and Diet Therapy. 9th ed. Philadelphia, PA: W.B. Saunders Company. 1996. p. 681-716. Contact: Available from W.B. Saunders Company. Order Fulfillment, 6277 Sea Harbor Drive, Orlando, FL 32887. (800) 545-2522. Fax (800) 874-6418 or (407) 352-3445. PRICE: $57.95 (as of 1996). ISBN: 0721658350. Summary: This chapter, from a textbook on food, nutrition, and diet therapy, covers nutritional care for diabetes mellitus and reactive hypoglycemia. The author describes different categories of glucose intolerance and then discusses the diagnosis of diabetes mellitus; insulin and counterregulatory hormones; the management of diabetes mellitus; the acute and long-term complications of the disease; surgery and diabetes; and diabetes and age-related issues. A final section addresses the implementation of nutrition selfmanagement. The chapter includes a brief glossary of related terms. 4 figures. 25 tables. 108 references.

•

Approach to the Elderly Patient with Hyperglycemia and Diabetes Mellitus Source: Kelley, W.N., ed. Textbook of Internal Medicine. 3rd ed. Vol 2. Philadelphia, PA: Lippincott-Raven Publishers. 1997. p. 2488-2494. Contact: Available from Lippincott-Raven Publishers. P.O. Box 1600, Hagerstown, MD 21741. (800) 638-3030 or (301) 714-2300. Fax (301) 824-7390. PRICE: $125.00 (2 volume edition) or $99.00 (single volume edition). ISBN: 0397515405 (2 volume set); 0397517297 (volume 1); 0397517300 (volume 2); 039751283x (paper). Summary: This chapter, from a textbook on internal medicine, describes for health professionals the diagnosis and management of hyperglycemia in elderly patients with diabetes mellitus. The authors point out that more than 20 percent of octogenarians have diabetes, and that type 2 diabetes accounts for about 90 percent of the cases of diabetes in older people. Topics include pathophysiology of age-related glucose intolerance and type 2 diabetes; presentation and diagnosis of type 2 diabetes; physical examination, taking a patient history, and laboratory assessment; differential diagnosis; and strategies for optimal care management. Although treatment of the older person with type 2 diabetes involves the same principles as those used with younger people, the author notes special considerations for the geriatric patient. Tables and figures outline common signs and symptoms of type 2 diabetes in older people; drugs that may affect glucose metabolism; complications that occur more often in the elderly; laboratory assessment; and a treatment algorithm. 2 figures. 4 tables. 7 references. (AA-M).

•

Nutrition Management of Adults with Diabetes Mellitus Source: in American Dietetic Association. Manual of Clinical Dietetics. Chicago, IL: American Dietetic Association. 1996. p. 649-682. Contact: Available from American Dietetic Association. 216 West Jackson Boulevard, Chicago, IL 60606. (800) 877-1600 or (312) 899-0040. Fax (312) 899-4899. PRICE: $59.95 for members, $70.00 for nonmembers. ISBN: 0880911530. Summary: This section of a manual of clinical dietetics addresses the nutrition management of adults with diabetes. According to the authors, nutrition intervention is the cornerstone of treatment for anyone who has diabetes or documented glucose intolerance. The general goal of medical nutrition therapy is to guide the person with diabetes in making food choices and behavioral changes that will help to improve

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diabetes self-management. Topics include the specific goals of nutrition management in diabetes, nutrition interventions for type 1 diabetes and for type 2 diabetes, carbohydrate distribution and insulin adjustment, exchange lists for meal planning, carbohydrate counting, blood glucose monitoring, hypoglycemia, sick day management, exercise, medical complications, and pregnancy. In addition, the authors provide information about caloric intake, protein, fat, carbohydrate, sweeteners, fiber, sodium, alcohol, and micronutrients. The chapter includes steps to follow in calculating a meal plan with exchanges. Numerous tables quantify some of the information in the chapter. A list of professional and client resources concludes the chapter. 16 tables. 42 references. (AA-M). •

Nutrition Support in Renal Failure Source: in American Dietetic Association. Manual of Clinical Dietetics. Chicago, IL: American Dietetic Association. 1996. p. 327-342. Contact: Available from American Dietetic Association. 216 West Jackson Boulevard, Chicago, IL 60606. (800) 877-1600 or (312) 899-0040. Fax (312) 899-4899. PRICE: $59.95 for members, $70.00 for nonmembers. ISBN: 0880911530. Summary: This section outlining guidelines for nutritional support in renal failure is from a manual that serves as a nutrition care guide for dietetics professionals, physicians, nurses, and other health professionals. The manual integrates current knowledge of nutrition, medical science, and food to set forth recommendations for healthy individuals and those for whom medical nutrition therapy (MNT) is indicated. The goal of nutrition support in renal failure is to achieve or maintain optimal nutritional status and preserve remaining kidney function through alterations in fluid, protein, and electrolyte intake. Nutrition support is used for patients with acute or chronic renal failure who are unable to meet nutrient requirements by oral intake. Impaired kidney function results in altered filtration, reabsorption, and excretion of metabolites and diminished urinary output. Hormonal function is also affected and may cause impaired vitamin D activation, impaired red blood cell synthesis, and glucose intolerance. The alterations differ with the cause of renal impairment; therefore, sodium, potassium, blood urea nitrogen (BUN), phosphate, urinary output, and the presence of acidosis must be monitored. The text notes the purpose, use, modifications, and adequacy of the diet. A separate section discusses enteral and parenteral nutrition, continuous arteriovenous hemofiltration, and the use of modified formulas (essential amino acids). 3 tables. 57 references. (AA-M).

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CHAPTER 6. MULTIMEDIA ON GLUCOSE INTOLERANCE Overview In this chapter, we show you how to keep current on multimedia sources of information on glucose intolerance. 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 glucose intolerance is the Combined Health Information Database. You will need to limit your search to “Videorecording” and “glucose intolerance” 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 “glucose intolerance” (or synonyms) into the “For these words:” box. The following is a typical result when searching for video recordings on glucose intolerance: •

Diabetes in Pregnancy Source: Baltimore, MD: Association of Women's Health, Obstetric, and Neonatal Nurses (AWHONN). Williams and Wilkins. 1992. Contact: Available from Williams and Wilkins Electronic Media. 351 W. Camden Street, Baltimore, MD 21201-2436. (800) 527-5597 or (410) 528-4223. Fax (800) 447-8438 or (410) 528-8550. PRICE: $165 (as of 1996). Catalog Number 17266-2. Summary: This videotape on diabetes in pregnancy is one of a series of professional nursing education programs on obstetrics. The tape covers the risk factors and pathophysiologic occurrences that result in glucose intolerance during pregnancy. Managing pregnant women with diabetes and the changes in insulin requirements during labor and the postpartum period are also addressed. (AA-M).

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CHAPTER 7. PERIODICALS AND NEWS ON GLUCOSE INTOLERANCE Overview In this chapter, we suggest a number of news sources and present various periodicals that cover glucose intolerance.

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

Gestational glucose intolerance may raise long-term cancer risk Source: Reuters Medical News Date: January 09, 2004

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Subclinical glucose intolerance increases risk of death Source: Reuters Medical News Date: March 29, 2001 The NIH

Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine. Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name. Market Wire Market Wire is more focused on technology than the other wires. To browse the latest press releases by topic, such as alternative medicine, biotechnology, fitness, healthcare, legal, nutrition, and pharmaceuticals, access Market Wire’s Medical/Health channel at http://www.marketwire.com/mw/release_index?channel=MedicalHealth. Or simply go to Market Wire’s home page at http://www.marketwire.com/mw/home, type “glucose intolerance” (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 “glucose intolerance” (or synonyms). If you know the name of a company that is relevant to glucose intolerance, 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 “glucose intolerance” (or synonyms).

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Academic Periodicals covering Glucose Intolerance Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to glucose intolerance. In addition to these sources, you can search for articles covering glucose intolerance 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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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 Institute10: •

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

•

National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25

•

National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm

•

National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm

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National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375

•

National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/

10

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/

•

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.11 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:12 •

Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html

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HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html

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NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html

•

Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/

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Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html

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Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html

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Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/

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Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html

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Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html

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Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html

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MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html

11

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). 12 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 Gateway13 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.14 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “glucose intolerance” (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 4911 14 937 40 68 5970

HSTAT15 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.16 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.17 Simply search by “glucose intolerance” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

13

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

14

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). 15 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 16 17

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 Biologists18 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.19 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.20 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.

Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are some examples that may interest you: •

CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.

•

Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.

18 Adapted 19

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. 20 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process.

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APPENDIX B. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. Since new guidelines on glucose intolerance can appear at any moment and be published by a number of sources, the best approach to finding guidelines is to systematically scan the Internetbased 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 glucose intolerance. 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 glucose intolerance. 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 “glucose intolerance”:

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Diabetes http://www.nlm.nih.gov/medlineplus/diabetes.html Genetic Brain Disorders http://www.nlm.nih.gov/medlineplus/geneticbraindisorders.html Lactose Intolerance http://www.nlm.nih.gov/medlineplus/lactoseintolerance.html Metabolic Disorders http://www.nlm.nih.gov/medlineplus/metabolicdisorders.html Metabolic Syndrome X http://www.nlm.nih.gov/medlineplus/metabolicsyndromex.html You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The 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 glucose intolerance. 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: •

Gluten-Free Diet Information Source: Flourtown, PA: Greater Philadelphia Celiac-Sprue Support Group. 1994. 3 p. Contact: Available from Greater Philadelphia Area Celiac-Sprue Support Group. 6318 Farmar Lane, Flourtown, PA 19031-1308. (215) 836-7518. PRICE: $20.00 for full information packet. Summary: This 3-page fact sheet presents, in chart form, a comparison of gluten-free and gluten-containing foods. The chart is broken down into 13 sections: flours; beverages; alcoholic beverages; cereals; starch (including pastas); soups; cheeses; desserts; dressings (including oils and spreads); spices (condiments); sweets; meats; and snack foods. Each section lists foods which are allowed, or gluten-free foods, and foods to avoid, which contain gluten. Designed for the person with celiac sprue or other glucose intolerance problems, this fact sheet provides detailed guidance for meal planning.

•

Greater Philadelphia Area Celiac-Sprue Support Group Information Packet Source: Flourtown, PA: Greater Philadelphia Celiac-Sprue Support Group. 1994. [166 p.].

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Contact: Available from Greater Philadelphia Area Celiac-Sprue Support Group. 6318 Farmar Lane, Flourtown, PA 19031-1308. (215) 836-7518. PRICE: $20.00. Summary: This information packet contains a wealth of materials to be used as a guide in following a gluten-free diet and in finding the sources for purchasing gluten-free foods. Included in the packet are brochures from organizations related to celiac disease; fact sheets about gluten-free foods; fact sheets about food additives; diet and meal planning information; information about monosodium glutamate; names and addresses of companies that manufacture and/or distribute gluten-free food; numerous recipes; a fact sheet on glucose intolerance; lists from a number of major manufacturers delineating which of their foods are gluten-free and which are not; and a chart outlining the grass family in which the gluten-gliadin fraction is found. The cover letter to the packet notes that the information was gathered by volunteers and is meant to be used as a guide only. 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 glucose intolerance. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •

AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats

•

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

•

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

•

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

•

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

•

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

•

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

Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to glucose intolerance. By consulting all of associations

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listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with glucose intolerance. 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 glucose intolerance. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797. Directory of Health Organizations The Directory of Health Organizations, provided by the National Library of Medicine Specialized Information Services, is a comprehensive source of information on associations. The Directory of Health Organizations database can be accessed via the Internet at http://www.sis.nlm.nih.gov/Dir/DirMain.html. It is composed of two parts: DIRLINE and Health Hotlines. The DIRLINE database comprises some 10,000 records of organizations, research centers, and government institutes and associations that primarily focus on health and biomedicine. To access DIRLINE directly, go to the following Web site: http://dirline.nlm.nih.gov/. Simply type in “glucose intolerance” (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 “glucose intolerance”. 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 “glucose intolerance” (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 “glucose intolerance” (or a synonym) into the search box, and click “Submit Query.”

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143

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.21

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

21

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)22: •

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/

22

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

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•

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

•

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

•

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

•

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

•

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/

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•

Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm

•

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

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GLUCOSE INTOLERANCE DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Abdominal fat: Fat (adipose tissue) that is centrally distributed between the thorax and pelvis and that induces greater health risk. [NIH] Abortion: 1. The premature expulsion from the uterus of the products of conception - of the embryo, or of a nonviable fetus. The four classic symptoms, usually present in each type of abortion, are uterine contractions, uterine haemorrhage, softening and dilatation of the cervix, and presentation or expulsion of all or part of the products of conception. 2. Premature stoppage of a natural or a pathological process. [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] Accommodation: Adjustment, especially that of the eye for various distances. [EU] Acculturation: Process of cultural change in which one group or members of a group assimilates various cultural patterns from another. [NIH] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Acidosis: A pathologic condition resulting from accumulation of acid or depletion of the alkaline reserve (bicarbonate content) in the blood and body tissues, and characterized by an increase in hydrogen ion concentration. [EU] Acne: A disorder of the skin marked by inflammation of oil glands and hair glands. [NIH] Acute lymphoblastic leukemia: ALL. A quickly progressing disease in which too many immature white blood cells called lymphoblasts are found in the blood and bone marrow. Also called acute lymphocytic leukemia. [NIH] Acute lymphocytic leukemia: ALL. A quickly progressing disease in which too many immature white blood cells called lymphoblasts are found in the blood and bone marrow. Also called acute lymphoblastic leukemia. [NIH] Acyl: Chemical signal used by bacteria to communicate. [NIH] Adaptation: 1. The adjustment of an organism to its environment, or the process by which it enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the intensity of light; the adjustment to such variations. 3. The decline in the frequency of firing 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]

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Adenoma: A benign epithelial tumor with a glandular organization. [NIH] Adenovirus: A group of viruses that cause respiratory tract and eye infections. Adenoviruses used in gene therapy are altered to carry a specific tumor-fighting gene. [NIH] Adipocytes: Fat-storing cells found mostly in the abdominal cavity and subcutaneous tissue. Fat is usually stored in the form of tryglycerides. [NIH] Adipose Tissue: Connective tissue composed of fat cells lodged in the meshes of areolar tissue. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] Adolescence: The period of life beginning with the appearance of secondary sex characteristics and terminating with the cessation of somatic growth. The years usually referred to as adolescence lie between 13 and 18 years of age. [NIH] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH] Adrenal Glands: Paired glands situated in the retroperitoneal tissues at the superior pole of each kidney. [NIH] Adrenal insufficiency: The reduced secretion of adrenal glands. [NIH] Adrenal Medulla: The inner part of the adrenal gland; it synthesizes, stores and releases catecholamines. [NIH] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adrenergic beta-Antagonists: Drugs that bind to but do not activate beta-adrenergic receptors thereby blocking the actions of beta-adrenergic agonists. Adrenergic betaantagonists are used for treatment of hypertension, cardiac arrythmias, angina pectoris, glaucoma, migraine headaches, and anxiety. [NIH] Adverse Effect: An unwanted side effect of treatment. [NIH] Aerobic: In biochemistry, reactions that need oxygen to happen or happen when oxygen is present. [NIH] Aerobic Exercise: A type of physical activity that includes walking, jogging, running, and dancing. Aerobic training improves the efficiency of the aerobic energy-producing systems that can improve cardiorespiratory endurance. [NIH] Aetiology: Study of the causes of disease. [EU] Afferent: Concerned with the transmission of neural impulse toward the central part of the nervous system. [NIH] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the 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

Dictionary 153

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] Age Factors: Age as a constituent element or influence contributing to the production of a result. It may be applicable to the cause or the effect of a circumstance. It is used with human or animal concepts but should be differentiated from aging, a physiological process, and time factors which refers only to the passage of time. [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] Agenesis: Lack of complete or normal development; congenital absence of an organ or part. [NIH]

Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Airway: A device for securing unobstructed passage of air into and out of the lungs during general anesthesia. [NIH] 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] 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] Allergen: An antigenic substance capable of producing immediate-type hypersensitivity (allergy). [EU] Allogeneic: Taken from different individuals of the same species. [NIH] Allograft: An organ or tissue transplant between two humans. [NIH] 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] 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

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herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Aluminum: A metallic element that has the atomic number 13, atomic symbol Al, and atomic weight 26.98. [NIH] Alveolar Process: The thickest and spongiest part of the maxilla and mandible hollowed out into deep cavities for the teeth. [NIH] Ameliorated: A changeable condition which prevents the consequence of a failure or accident from becoming as bad as it otherwise would. [NIH] Amenorrhea: Absence of menstruation. [NIH] Amino acid: Any organic compound containing an amino (-NH2 and a carboxyl (- COOH) group. The 20 a-amino acids listed in the accompanying table are the amino acids from which proteins are synthesized by formation of peptide bonds during ribosomal translation of messenger RNA; all except glycine, which is not optically active, have the L configuration. Other amino acids occurring in proteins, such as hydroxyproline in collagen, are formed by posttranslational enzymatic modification of amino acids residues in polypeptide chains. There are also several important amino acids, such as the neurotransmitter y-aminobutyric acid, that have no relation to proteins. Abbreviated AA. [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] Amniotic Fluid: Amniotic cavity fluid which is produced by the amnion and fetal lungs and kidneys. [NIH] Ampulla: A sac-like enlargement of a canal or duct. [NIH] Amyloid: A general term for a variety of different proteins that accumulate as extracellular fibrils of 7-10 nm and have common structural features, including a beta-pleated sheet conformation and the ability to bind such dyes as Congo red and thioflavine (Kandel, Schwartz, and Jessel, Principles of Neural Science, 3rd ed). [NIH] Amyloidosis: A group of diseases in which protein is deposited in specific organs (localized amyloidosis) or throughout the body (systemic amyloidosis). Amyloidosis may be either primary (with no known cause) or secondary (caused by another disease, including some types of cancer). Generally, primary amyloidosis affects the nerves, skin, tongue, joints, heart, and liver; secondary amyloidosis often affects the spleen, kidneys, liver, and adrenal glands. [NIH] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Anaphylatoxins: The family of peptides C3a, C4a, C5a, and C5a des-arginine produced in the serum during complement activation. They produce smooth muscle contraction, mast cell histamine release, affect platelet aggregation, and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from strongest to weakest is C5a, C3a, C4a, and C5a des-arginine. The latter is the so-called "classical" anaphylatoxin but shows no spasmogenic activity though it contains some chemotactic ability. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Androgenic: Producing masculine characteristics. [EU] Androgens: A class of sex hormones associated with the development and maintenance of

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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] Androstenedione: A steroid with androgenic properties that is produced in the testis, ovary, and adrenal cortex. It is a precursor to testosterone and other androgenic hormones. [NIH] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [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] Angina: Chest pain that originates in the heart. [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] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Aniridia: A congenital abnormality in which there is only a rudimentary iris. This is due to the failure of the optic cup to grow. Aniridia also occurs in a hereditary form, usually autosomal dominant. [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] Anovulation: Suspension or cessation of ovulation in animals and humans. [NIH] Antagonism: Interference with, or inhibition of, the growth of a living organism by another living organism, due either to creation of unfavorable conditions (e. g. exhaustion of food supplies) or to production of a specific antibiotic substance (e. g. penicillin). [NIH] Antiallergic: Counteracting allergy or allergic conditions. [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]

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Antidiuretic: Suppressing the rate of urine formation. [EU] Antifungal: Destructive to fungi, or suppressing their reproduction or growth; effective against fungal infections. [EU] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. [NIH] Antihypertensive: An agent that reduces high blood pressure. [EU] Antihypertensive Agents: Drugs used in the treatment of acute or chronic hypertension regardless of pharmacological mechanism. Among the antihypertensive agents are diuretics (especially diuretics, thiazide), adrenergic beta-antagonists, adrenergic alpha-antagonists, angiotensin-converting enzyme inhibitors, calcium channel blockers, ganglionic blockers, and vasodilator agents. [NIH] Anti-infective: An agent that so acts. [EU] Anti-Infective Agents: Substances that prevent infectious agents or organisms from spreading or kill infectious agents in order to prevent the spread of infection. [NIH] 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] Aplastic anemia: A condition in which the bone marrow is unable to produce blood cells. [NIH]

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] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Arteriosclerosis: Thickening and loss of elasticity of arterial walls. Atherosclerosis is the most common form of arteriosclerosis and involves lipid deposition and thickening of the intimal cell layers within arteries. Additional forms of arteriosclerosis involve calcification of the media of muscular arteries (Monkeberg medial calcific sclerosis) and thickening of the walls of small arteries or arterioles due to cell proliferation or hyaline deposition (arteriolosclerosis). [NIH]

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Arteriovenous: Both arterial and venous; pertaining to or affecting an artery and a vein. [EU] Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH] Aspiration: The act of inhaling. [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] Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] Attenuated: Strain with weakened or reduced virulence. [NIH] Attenuation: Reduction of transmitted sound energy or its electrical equivalent. [NIH] Aural: Pertaining to or perceived by the ear, as an aural stimulus. [EU] Autoantibodies: Antibodies that react with self-antigens (autoantigens) of the organism that produced them. [NIH] Autoantigens: Endogenous tissue constituents that have the ability to interact with autoantibodies and cause an immune response. [NIH] 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] Autologous: Taken from an individual's own tissues, cells, or DNA. [NIH] Autologous bone marrow transplantation: A procedure in which bone marrow is removed from a person, stored, and then given back to the person after intensive treatment. [NIH] Autosuggestion: Suggestion coming from the subject himself. [NIH] Azotemia: An excess of urea or other nitrogenous compounds in the blood. [EU] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacterial Physiology: Physiological processes and activities of bacteria. [NIH] Bactericidal: Substance lethal to bacteria; substance capable of killing bacteria. [NIH] Bacteriophage: A virus whose host is a bacterial cell; A virus that exclusively infects bacteria. It generally has a protein coat surrounding the genome (DNA or RNA). One of the coliphages most extensively studied is the lambda phage, which is also one of the most important. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]

Beta-pleated: Particular three-dimensional pattern of amyloidoses. [NIH] Bilateral: Affecting both the right and left side of body. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bile Acids: Acids made by the liver that work with bile to break down fats. [NIH] Bile Acids and Salts: Steroid acids and salts. The primary bile acids are derived from

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cholesterol in the liver and usually conjugated with glycine or taurine. The secondary bile acids are further modified by bacteria in the intestine. They play an important role in the digestion and absorption of fat. They have also been used pharmacologically, especially in the treatment of gallstones. [NIH] Bile duct: A tube through which bile passes in and out of the liver. [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] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biological therapy: Treatment to stimulate or restore the ability of the immune system to fight infection and disease. Also used to lessen side effects that may be caused by some cancer treatments. Also known as immunotherapy, biotherapy, or biological response modifier (BRM) therapy. [NIH] Biomarkers: Substances sometimes found in an increased amount in the blood, other body fluids, or tissues and that may suggest the presence of some types of cancer. Biomarkers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and GI tract cancers), and PSA (prostate cancer). Also called tumor markers. [NIH] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Bladder: The organ that stores urine. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Glucose: Glucose in blood. [NIH] Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood urea: A waste product in the blood that comes from the breakdown of food protein. The kidneys filter blood to remove urea. As kidney function decreases, the BUN level increases. [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] 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]

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Body Mass Index: One of the anthropometric measures of body mass; it has the highest correlation with skinfold thickness or body density. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone Marrow Transplantation: The transference of bone marrow from one human or animal to another. [NIH] Bone Resorption: Bone loss due to osteoclastic activity. [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] Breeding: The science or art of changing the constitution of a population of plants or animals through sexual reproduction. [NIH] Bronchi: The larger air passages of the lungs arising from the terminal bifurcation of the trachea. [NIH] Bronchodilator: A drug that relaxes the smooth muscles in the constricted airway. [NIH] Bypass: A surgical procedure in which the doctor creates a new pathway for the flow of body fluids. [NIH] Caesarean section: A surgical incision through the abdominal and uterine walls in order to deliver a baby. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Calcium channel blocker: A drug used to relax the blood vessel and heart muscle, causing pressure inside blood vessels to drop. It also can regulate heart rhythm. [NIH] Calcium Channel Blockers: A class of drugs that act by selective inhibition of calcium influx through cell membranes or on the release and binding of calcium in intracellular pools. Since they are inducers of vascular and other smooth muscle relaxation, they are used in the drug therapy of hypertension and cerebrovascular spasms, as myocardial protective agents, and in the relaxation of uterine spasms. [NIH] Calcium Channels: Voltage-dependent cell membrane glycoproteins selectively permeable to calcium ions. They are categorized as L-, T-, N-, P-, Q-, and R-types based on the activation and inactivation kinetics, ion specificity, and sensitivity to drugs and toxins. The L- and T-types are present throughout the cardiovascular and central nervous systems and the N-, P-, Q-, & R-types are located in neuronal tissue. [NIH] Caloric intake: Refers to the number of calories (energy content) consumed. [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;

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called also vas capillare. [EU] 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] 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] Carcinoid: A type of tumor usually found in the gastrointestinal system (most often in the appendix), and sometimes in the lungs or other sites. Carcinoid tumors are usually benign. [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] Cardiorespiratory: Relating to the heart and lungs and their function. [EU] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] Carnitine: Constituent of striated muscle and liver. It is used therapeutically to stimulate gastric and pancreatic secretions and in the treatment of hyperlipoproteinemias. [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] Cataract: An opacity, partial or complete, of one or both eyes, on or in the lens or capsule, especially an opacity impairing vision or causing blindness. The many kinds of cataract are classified by their morphology (size, shape, location) or etiology (cause and time of occurrence). [EU] Catecholamines: A general class of ortho-dihydroxyphenylalkylamines derived from tyrosine. [NIH] Catheters: A small, flexible tube that may be inserted into various parts of the body to inject or remove liquids. [NIH] Causal: Pertaining to a cause; directed against a cause. [EU] Cause of Death: Factors which produce cessation of all vital bodily functions. They can be analyzed from an epidemiologic viewpoint. [NIH] Celiac Disease: A disease characterized by intestinal malabsorption and precipitated by gluten-containing foods. The intestinal mucosa shows loss of villous structure. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Cycle: The complex series of phenomena, occurring between the end of one cell division and the end of the next, by which cellular material is divided between daughter cells. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing

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specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell 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] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] 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] Chemotactic Factors: Chemical substances that attract or repel cells or organisms. The concept denotes especially those factors released as a result of tissue injury, invasion, or immunologic activity, that attract leukocytes, macrophages, or other cells to the site of infection or insult. [NIH] Chemotaxis: The movement of cells or organisms toward or away from a substance in response to its concentration gradient. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] Chin: The anatomical frontal portion of the mandible, also known as the mentum, that contains the line of fusion of the two separate halves of the mandible (symphysis menti). This line of fusion divides inferiorly to enclose a triangular area called the mental protuberance. On each side, inferior to the second premolar tooth, is the mental foramen for the passage of blood vessels and a nerve. [NIH] Cholestasis: Impairment of biliary flow at any level from the hepatocyte to Vater's ampulla. [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] Chromaffin System: The cells of the body which stain with chromium salts. They occur along the sympathetic nerves, in the adrenal gland, and in various other organs. [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] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all

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human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic Disease: Disease or ailment of long duration. [NIH] Chronic 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] 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] Circadian: Repeated more or less daily, i. e. on a 23- to 25-hour cycle. [NIH] Circadian Rhythm: The regular recurrence, in cycles of about 24 hours, of biological processes or activities, such as sensitivity to drugs and stimuli, hormone secretion, sleeping, feeding, etc. This rhythm seems to be set by a 'biological clock' which seems to be set by recurring daylight and darkness. [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] Cirrhosis: A type of chronic, progressive liver disease. [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] Clamp: A u-shaped steel rod used with a pin or wire for skeletal traction in the treatment of certain fractures. [NIH] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]

Clinical 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] Cohort Studies: Studies in which subsets of a defined population are identified. These groups may or may not be exposed to factors hypothesized to influence the probability of the occurrence of a particular disease or other outcome. Cohorts are defined populations which, as a whole, are followed in an attempt to determine distinguishing subgroup characteristics. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline,

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hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Collapse: 1. A state of extreme prostration and depression, with failure of circulation. 2. Abnormal falling in of the walls of any part of organ. [EU] Colloidal: Of the nature of a colloid. [EU] Common Bile Duct: The largest biliary duct. It is formed by the junction of the cystic duct and the hepatic duct. [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU] Concomitant: Accompanying; accessory; joined with another. [EU] 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] 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] Constipation: Infrequent or difficult evacuation of feces. [NIH] Constitutional: 1. Affecting the whole constitution of the body; not local. 2. Pertaining to the constitution. [EU] Constriction: The act of constricting. [NIH] Consultation: A deliberation between two or more physicians concerning the diagnosis and the proper method of treatment in a case. [NIH] Contraceptive: An agent that diminishes the likelihood of or prevents conception. [EU] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Control group: In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works. [NIH] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary 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] Corticosteroid: Any of the steroids elaborated by the adrenal cortex (excluding the sex 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

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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] Creatinine: A compound that is excreted from the body in urine. Creatinine levels are measured to monitor kidney function. [NIH] Cultured cells: Animal or human cells that are grown in the laboratory. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] 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] Cyclosporine: A drug used to help reduce the risk of rejection of organ and bone marrow transplants by the body. It is also used in clinical trials to make cancer cells more sensitive to anticancer drugs. [NIH] Cystic Duct: The tube that carries bile from the gallbladder into the common bile duct and the small intestine. [NIH] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a 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] Cytotoxicity: Quality of being capable of producing a specific toxic action upon cells of special organs. [NIH] Dairy Products: Raw and processed or manufactured milk and milk-derived products. These are usually from cows (bovine) but are also from goats, sheep, reindeer, and water buffalo. [NIH] Data Collection: Systematic gathering of data for a particular purpose from various sources, including questionnaires, interviews, observation, existing records, and electronic devices. The process is usually preliminary to statistical analysis of the data. [NIH] Decompensation: Failure of compensation; cardiac decompensation is marked by dyspnea, venous engorgement, and edema. [EU] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Delivery of Health Care: The concept concerned with all aspects of providing and distributing health services to a patient population. [NIH] Demography: Statistical interpretation and description of a population with reference to distribution, composition, or structure. [NIH] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Desensitization: The prevention or reduction of immediate hypersensitivity reactions by administration of graded doses of allergen; called also hyposensitization and immunotherapy. [EU]

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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] Developing Countries: Countries in the process of change directed toward economic growth, that is, an increase in production, per capita consumption, and income. The process of economic growth involves better utilization of natural and human resources, which results in a change in the social, political, and economic structures. [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] Diabetic Foot: Ulcers of the foot as a complication of diabetes. Diabetic foot, often with infection, is a common serious complication of diabetes and may require hospitalization and disfiguring surgery. The foot ulcers are probably secondary to neuropathies and vascular problems. [NIH] Diabetic Retinopathy: Retinopathy associated with diabetes mellitus, which may be of the background type, progressively characterized by microaneurysms, interretinal punctuate macular edema, or of the proliferative type, characterized by neovascularization of the retina and optic disk, which may project into the vitreous, proliferation of fibrous tissue, vitreous hemorrhage, and retinal detachment. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Dialyzer: A part of the hemodialysis machine. (See hemodialysis under dialysis.) The dialyzer has two sections separated by a membrane. One section holds dialysate. The other holds the patient's blood. [NIH] 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] Dietary Fiber: The remnants of plant cell walls that are resistant to digestion by the alimentary enzymes of man. It comprises various polysaccharides and lignins. [NIH] Dietetics: The study and regulation of the diet. [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] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Discrete: Made up of separate parts or characterized by lesions which do not become blended; not running together; separate. [NIH]

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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] Disposition: A tendency either physical or mental toward certain diseases. [EU] Dissection: Cutting up of an organism for study. [NIH] Diuretic: A drug that increases the production of urine. [NIH] Diuretics, Thiazide: Diuretics characterized as analogs of 1,2,4-benzothiadiazine-1,1dioxide. All have a common mechanism of action and differ primarily in the dose required to produce a given effect. They act directly on the kidney to increase the excretion of sodium chloride and water and also increase excretion of potassium ions. [NIH] Dose-dependent: Refers to the effects of treatment with a drug. If the effects change when the dose of the drug is changed, the effects are said to be dose dependent. [NIH] Drive: A state of internal activity of an organism that is a necessary condition before a given stimulus will elicit a class of responses; e.g., a certain level of hunger (drive) must be present before food will elicit an eating response. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] Duct: A tube through which body fluids pass. [NIH] Duodenum: The first part of the small intestine. [NIH] Dyes: Chemical substances that are used to stain and color other materials. The coloring may or may not be permanent. Dyes can also be used as therapeutic agents and test reagents in medicine and scientific research. [NIH] 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] Dyspnea: Difficult or labored breathing. [NIH] Dystrophic: Pertaining to toxic habitats low in nutrients. [NIH] Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [NIH] Educational Status: Educational attainment or level of education of individuals. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Elastic: Susceptible of resisting and recovering from stretching, compression or distortion

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applied by a force. [EU] Elastin: The protein that gives flexibility to tissues. [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] 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] Enalapril: An angiotensin-converting enzyme inhibitor that is used to treat hypertension. [NIH]

Encephalopathy: A disorder of the brain that can be caused by disease, injury, drugs, or chemicals. [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] 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] Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [NIH] Endopeptidases: A subclass of peptide hydrolases. They are classified primarily by their catalytic mechanism. Specificity is used only for identification of individual enzymes. They comprise the serine endopeptidases, EC 3.4.21; cysteine endopeptidases, EC 3.4.22; aspartic endopeptidases, EC 3.4.23, metalloendopeptidases, EC 3.4.24; and a group of enzymes yet to be assigned to any of the above sub-classes, EC 3.4.99. EC 3.4.-. [NIH] 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]

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Endothelium, Vascular: Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components from interstitium to lumen; this function has been most intensively studied in the blood capillaries. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] Endotoxic: Of, relating to, or acting as an endotoxin (= a heat-stable toxin, associated with the outer membranes of certain gram-negative bacteria. Endotoxins are not secreted and are released only when the cells are disrupted). [EU] Endotoxins: Toxins closely associated with the living cytoplasm or cell wall of certain microorganisms, which do not readily diffuse into the culture medium, but are released upon lysis of the cells. [NIH] End-stage renal: Total chronic kidney failure. When the kidneys fail, the body retains fluid and harmful wastes build up. A person with ESRD needs treatment to replace the work of the failed kidneys. [NIH] Energy balance: Energy is the capacity of a body or a physical system for doing work. Energy balance is the state in which the total energy intake equals total energy needs. [NIH] Enteral Nutrition: Nutritional support given via the alimentary canal or any route connected to the gastrointestinal system (i.e., the enteral route). This includes oral feeding, sip feeding, and tube feeding using nasogastric, gastrostomy, and jejunostomy tubes. [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] Epidemic: Occurring suddenly in numbers clearly in excess of normal expectancy; said especially of infectious diseases but applied also to any disease, injury, or other healthrelated event occurring in such outbreaks. [EU] Epidemiologic Studies: Studies designed to examine associations, commonly, hypothesized causal relations. They are usually concerned with identifying or measuring the effects of risk factors or exposures. The common types of analytic study are case-control studies, cohort studies, and cross-sectional studies. [NIH] Epidemiological: Relating to, or involving epidemiology. [EU] 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] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach.

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[NIH]

Estrogen: One of the two female sex hormones. [NIH] Estrogen receptor: ER. Protein found on some cancer cells to which estrogen will attach. [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] Ethnic Groups: A group of people with a common cultural heritage that sets them apart from others in a variety of social relationships. [NIH] Evacuation: An emptying, as of the bowels. [EU] Evoke: The electric response recorded from the cerebral cortex after stimulation of a peripheral sense organ. [NIH] Excipients: Usually inert substances added to a prescription in order to provide suitable consistency to the dosage form; a binder, matrix, base or diluent in pills, tablets, creams, salves, etc. [NIH] Exercise Test: Controlled physical activity, more strenuous than at rest, which is performed in order to allow assessment of physiological functions, particularly cardiovascular and pulmonary, but also aerobic capacity. Maximal (most intense) exercise is usually required but submaximal exercise is also used. The intensity of exercise is often graded, using criteria such as rate of work done, oxygen consumption, and heart rate. Physiological data obtained from an exercise test may be used for diagnosis, prognosis, and evaluation of disease severity, and to evaluate therapy. Data may also be used in prescribing exercise by determining a person's exercise capacity. [NIH] Exercise Tolerance: The exercise capacity of an individual as measured by endurance (maximal exercise duration and/or maximal attained work load) during an exercise test. [NIH]

Exhaustion: The feeling of weariness of mind and body. [NIH] Exocrine: Secreting outwardly, via a duct. [EU] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] 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] Extracorporeal: Situated or occurring outside the body. [EU] Eye Infections: Infection, moderate to severe, caused by bacteria, fungi, or viruses, which occurs either on the external surface of the eye or intraocularly with probable inflammation, visual impairment, or blindness. [NIH] Facial: Of or pertaining to the face. [EU] 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] Fat: Total lipids including phospholipids. [NIH] Fatty Liver: The buildup of fat in liver cells. The most common cause is alcoholism. Other

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causes include obesity, diabetes, and pregnancy. Also called steatosis. [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] Ferritin: An iron-containing protein complex that is formed by a combination of ferric iron with the protein apoferritin. [NIH] Fertilization in Vitro: Fertilization of an egg outside the body when the egg is normally fertilized in the body. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [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] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Filtration: The passage of a liquid through a filter, accomplished by gravity, pressure, or vacuum (suction). [EU] Flavoring Agents: Substances added to foods and medicine to improve the quality of taste. [NIH]

Fluid Therapy: Therapy whose basic objective is to restore the volume and composition of the body fluids to normal with respect to water-electrolyte balance. Fluids may be administered intravenously, orally, by intermittent gavage, or by hypodermoclysis. [NIH] Fluoxetine: The first highly specific serotonin uptake inhibitor. It is used as an antidepressant and often has a more acceptable side-effects profile than traditional antidepressants. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Food Additives: Substances which are of little or no nutritive value, but are used in the processing or storage of foods or animal feed, especially in the developed countries; includes antioxidants, food preservatives, food coloring agents, flavoring agents, anti-infective agents (both plain and local), vehicles, excipients and other similarly used substances. Many of the same substances are pharmaceutic aids when added to pharmaceuticals rather than to foods. [NIH]

Food Coloring Agents: Natural or synthetic dyes used as coloring agents in processed foods. [NIH] Food Preservatives: Substances capable of inhibiting, retarding or arresting the process of fermentation, acidification or other deterioration of foods. [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] Forearm: The part between the elbow and the wrist. [NIH] Free Radicals: Highly reactive molecules with an unsatisfied electron valence pair. Free

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radicals are produced in both normal and pathological processes. They are proven or suspected agents of tissue damage in a wide variety of circumstances including radiation, damage from environment chemicals, and aging. Natural and pharmacological prevention of free radical damage is being actively investigated. [NIH] Fructosamine: An amino sugar formed when glucose non-enzymatically reacts with the Nterminal amino group of proteins. The fructose moiety is dervied from glucose by the "classical" Amadori rearrangement. [NIH] Fructose Intolerance: An autosomal recessive fructose metabolism disorder due to deficient fructose-1-phosphate aldolase (EC 2.1.2.13) activity, resulting in accumulation of fructose-1phosphate. The accumulated fructose-1-phosphate inhibits glycogenolysis and gluconeogenesis, causing severe hypoglycemia following ingestion of fructose. Prolonged fructose ingestion in infants leads ultimately to hepatic failure and death. Patients develop a strong distaste for sweet food, and avoid a chronic course of the disease by remaining on a fructose- and sucrose-free diet. [NIH] Fundus: The larger part of a hollow organ that is farthest away from the organ's opening. The bladder, gallbladder, stomach, uterus, eye, and cavity of the middle ear all have a fundus. [NIH] Galactosemia: Buildup of galactose in the blood. Caused by lack of one of the enzymes needed to break down galactose into glucose. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Ganglion: 1. A knot, or knotlike mass. 2. A general term for a group of nerve cell bodies located outside the central nervous system; occasionally applied to certain nuclear groups within the brain or spinal cord, e.g. basal ganglia. 3. A benign cystic tumour occurring on a aponeurosis or tendon, as in the wrist or dorsum of the foot; it consists of a thin fibrous capsule enclosing a clear mucinous fluid. [EU] Ganglionic Blockers: Agents having as their major action the interruption of neural transmission at nicotinic receptors on postganglionic autonomic neurons. Because their actions are so broad, including blocking of sympathetic and parasympathetic systems, their therapeutic use has been largely supplanted by more specific drugs. They may still be used in the control of blood pressure in patients with acute dissecting aortic aneurysm and for the induction of hypotension in surgery. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gastric: Having to do with the stomach. [NIH] Gastric Inhibitory Polypeptide: A gastrointestinal hormone consisting of a 43-amino acid polypeptide (molecular weight 5105). It inhibits gastric secretion and motility and stimulates release of insulin. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]

Gastroenterology: A subspecialty of internal medicine concerned with the study of the physiology and diseases of the digestive system and related structures (esophagus, liver, gallbladder, and pancreas). [NIH] Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gastrostomy: Creation of an artificial external opening into the stomach for nutritional support or gastrointestinal compression. [NIH]

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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] Gene Therapy: The introduction of new genes into cells for the purpose of treating disease by restoring or adding gene expression. Techniques include insertion of retroviral vectors, transfection, homologous recombination, and injection of new genes into the nuclei of single cell embryos. The entire gene therapy process may consist of multiple steps. The new genes may be introduced into proliferating cells in vivo (e.g., bone marrow) or in vitro (e.g., fibroblast cultures) and the modified cells transferred to the site where the gene expression is required. Gene therapy may be particularly useful for treating enzyme deficiency diseases, hemoglobinopathies, and leukemias and may also prove useful in restoring drug sensitivity, particularly for leukemia. [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] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Geographic Locations: All of the continents and every country situated within, the United States and each of the constituent states arranged by region, Canada and each of its provinces, Australia and each of its states, the major bodies of water and major islands on both hemispheres, and selected major cities. Although the geographic locations are not printed in index medicus as main headings, in indexing they are significant in epidemiologic studies and historical articles and for locating administrative units in education and the delivery of health care. [NIH] Geriatric: Pertaining to the treatment of the aged. [EU] Germ Cells: The reproductive cells in multicellular organisms. [NIH] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] Gestational: Psychosis attributable to or occurring during pregnancy. [NIH] 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] Gingivitis: Inflammation of the gingivae. Gingivitis associated with bony changes is referred to as periodontitis. Called also oulitis and ulitis. [EU] 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] Gliadin: Simple protein, one of the prolamines, derived from the gluten of wheat, rye, etc. May be separated into 4 discrete electrophoretic fractions. It is the toxic factor associated with celiac disease. [NIH] Glipizide: An oral hypoglycemic agent which is rapidly absorbed and completely metabolized. [NIH] Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus. [EU]

Glomeruli: Plural of glomerulus. [NIH]

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Glomerulosclerosis: Scarring of the glomeruli. It may result from diabetes mellitus (diabetic glomerulosclerosis) or from deposits in parts of the glomerulus (focal segmental glomerulosclerosis). The most common signs of glomerulosclerosis are proteinuria and kidney failure. [NIH] Glomerulus: A tiny set of looping blood vessels in the nephron where blood is filtered in the kidney. [NIH] 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 tolerance: The power of the normal liver to absorb and store large quantities of glucose and the effectiveness of intestinal absorption of glucose. The glucose tolerance test is a metabolic test of carbohydrate tolerance that measures active insulin, a hepatic function based on the ability of the liver to absorb glucose. The test consists of ingesting 100 grams of glucose into a fasting stomach; blood sugar should return to normal in 2 to 21 hours after ingestion. [NIH] Glucose Tolerance Test: Determination of whole blood or plasma sugar in a fasting state before and at prescribed intervals (usually 1/2 hr, 1 hr, 3 hr, 4 hr) after taking a specified amount (usually 100 gm orally) of glucose. [NIH] Glucuronic Acid: Derivatives of uronic acid found throughout the plant and animal kingdoms. They detoxify drugs and toxins by conjugating with them to form glucuronides in the liver which are more water-soluble metabolites that can be easily eliminated from the body. [NIH] Glutamate: Excitatory neurotransmitter of the brain. [NIH] Glutathione Peroxidase: An enzyme catalyzing the oxidation of 2 moles of glutathione in the presence of hydrogen peroxide to yield oxidized glutathione and water. EC 1.11.1.9. [NIH]

Gluten: The protein of wheat and other grains which gives to the dough its tough elastic character. [EU] Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. [NIH] Glycogen: A sugar stored in the liver and muscles. It releases glucose into the blood when cells need it for energy. Glycogen is the chief source of stored fuel in the body. [NIH] Glycogen Storage Disease: A group of inherited metabolic disorders involving the enzymes responsible for the synthesis and degradation of glycogen. In some patients, prominent liver involvement is presented. In others, more generalized storage of glycogen occurs, sometimes with prominent cardiac involvement. [NIH] Glycogen Synthase: An enzyme that catalyzes the transfer of D-glucose from UDPglucose into 1,4-alpha-D-glucosyl chains. EC 2.4.1.11. [NIH] Glycolysis: The pathway by which glucose is catabolized into two molecules of pyruvic acid with the generation of ATP. [NIH] Glycoproteins: Conjugated protein-carbohydrate compounds including mucins, mucoid,

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and amyloid glycoproteins. [NIH] Glycosaminoglycans: Heteropolysaccharides which contain an N-acetylated hexosamine in a characteristic repeating disaccharide unit. The repeating structure of each disaccharide involves alternate 1,4- and 1,3-linkages consisting of either N-acetylglucosamine or Nacetylgalactosamine. [NIH] Glycosuria: The presence of glucose in the urine; especially the excretion of an abnormally large amount of sugar (glucose) in the urine, i.e., more than 1 gm. in 24 hours. [EU] Gonad: A sex organ, such as an ovary or a testicle, which produces the gametes in most multicellular animals. [NIH] Gonadal: Pertaining to a gonad. [EU] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] 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] Graft Survival: The survival of a graft in a host, the factors responsible for the survival and the changes occurring within the graft during growth in the host. [NIH] Gravidity: Pregnancy; the condition of being pregnant, without regard to the outcome. [EU] Growth factors: Substances made by the body that function to regulate cell division and cell survival. Some growth factors are also produced in the laboratory and used in biological therapy. [NIH] Guanylate Cyclase: An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2. [NIH] Habitual: Of the nature of a habit; according to habit; established by or repeated by force of habit, customary. [EU] Hawaii: A group of islands in Polynesia, in the north central Pacific Ocean, comprising eight major and 114 minor islands, largely volcanic and coral. Its capital is Honolulu. It was first reached by Polynesians about 500 A.D. It was discovered and named the Sandwich Islands in 1778 by Captain Cook. The islands were united under the rule of King Kamehameha 1795-1819 and requested annexation to the United States in 1893 when a provisional government was set up. Hawaii was established as a territory in 1900 and admitted as a state in 1959. The name is from the Polynesian Owhyhii, place of the gods, with reference to the two volcanoes Mauna Kea and Mauna Loa, regarded as the abode of the gods. (From Webster's New Geographical Dictionary, 1988, p493 & Room, Brewer's Dictionary of Names, 1992, p2330 [NIH] Health Behavior: Behaviors expressed by individuals to protect, maintain or promote their health status. For example, proper diet, and appropriate exercise are activities perceived to influence health status. Life style is closely associated with health behavior and factors influencing life style are socioeconomic, educational, and cultural. [NIH] Health Services: Services for the diagnosis and treatment of disease and the maintenance of health. [NIH] Health Status: The level of health of the individual, group, or population as subjectively assessed by the individual or by more objective measures. [NIH] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH]

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Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemochromatosis: A disease that occurs when the body absorbs too much iron. The body stores the excess iron in the liver, pancreas, and other organs. May cause cirrhosis of the liver. Also called iron overload disease. [NIH] 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] 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] 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]

Heparin: Heparinic acid. A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts. [NIH] Hepatic: Refers to the liver. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatobiliary: Pertaining to the liver and the bile or the biliary ducts. [EU] Hepatocellular: Pertaining to or affecting liver cells. [EU] Hepatocyte: A liver cell. [NIH] Hepatology: The field of medicine concerned with the functions and disorders of the liver. [NIH]

Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] 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]

Heterozygotes: Having unlike alleles at one or more corresponding loci on homologous chromosomes. [NIH]

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Hirsutism: Excess hair in females and children with an adult male pattern of distribution. The concept does not include hypertrichosis, which is localized or generalized excess hair. [NIH]

Histology: The study of tissues and cells under a microscope. [NIH] Homeobox: Distinctive sequence of DNA bases. [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] Homozygotes: An individual having a homozygous gene pair. [NIH] 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] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [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] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU] Hydroxylysine: A hydroxylated derivative of the amino acid lysine that is present in certain collagens. [NIH] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hyperandrogenism: A state characterized or caused by an excessive secretion of androgens by the adrenal cortex, ovaries, or testes. The clinical significance in males is negligible, so the term is used most commonly with reference to the female. The common manifestations in women are hirsutism and virilism. It is often caused by ovarian disease (particularly the polycystic ovary syndrome) and by adrenal diseases (particularly adrenal gland hyperfunction). [NIH] Hypercholesterolemia: Abnormally high levels of cholesterol in the blood. [NIH] Hyperglycemia: Abnormally high blood sugar. [NIH] Hyperlipidaemia: A general term for elevated concentrations of any or all of the lipids in the plasma, including hyperlipoproteinaemia, hypercholesterolaemia, etc. [EU] Hyperlipidemia: An excess of lipids in the blood. [NIH] Hyperlipoproteinemia: Metabolic disease characterized by elevated plasma cholesterol and/or triglyceride levels. The inherited form is attributed to a single gene mechanism. [NIH] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions

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upon subsequent exposure to that particular antigen. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hyperthyroidism: Excessive functional activity of the thyroid gland. [NIH] Hypertriglyceridemia: Condition of elevated triglyceride concentration in the blood; an inherited form occurs in familial hyperlipoproteinemia IIb and hyperlipoproteinemia type IV. It has been linked to higher risk of heart disease and arteriosclerosis. [NIH] Hypertrophy: General increase in bulk of a part or organ, not due to tumor formation, nor to an increase in the number of cells. [NIH] Hypoglycemia: Abnormally low blood sugar [NIH] Hypoglycemic: An orally active drug that produces a fall in blood glucose concentration. [NIH]

Hypoglycemic Agents: Agents which lower the blood glucose level. [NIH] Hypogonadism: Condition resulting from or characterized by abnormally decreased functional activity of the gonads, with retardation of growth and sexual development. [NIH] 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] 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] Iatrogenic: Resulting from the activity of physicians. Originally applied to disorders induced in the patient by autosuggestion based on the physician's examination, manner, or discussion, the term is now applied to any adverse condition in a patient occurring as the result of treatment by a physician or surgeon, especially to infections acquired by the patient during the course of treatment. [EU] Idiopathic: Describes a disease of unknown cause. [NIH] Ileal: Related to the ileum, the lowest end of the small intestine. [NIH] Ileum: The lower end of the small intestine. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]

Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] 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] Immunogenic: Producing immunity; evoking an immune response. [EU] Immunoglobulin: A protein that acts as an antibody. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunology: The study of the body's immune system. [NIH]

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Immunophilins: Members of a family of highly conserved proteins which are all cis-trans peptidyl-prolyl isomerases (peptidylprolyl isomerase). They bind the immunosuppressant drugs cyclosporine; tacrolimus and sirolimus. They possess rotomase activity, which is inhibited by the immunosuppressant drugs that bind to them. EC 5.2.1.- [NIH] Immunosuppressant: An agent capable of suppressing immune responses. [EU] Immunosuppression: Deliberate prevention or diminution of the host's immune response. It may be nonspecific as in the administration of immunosuppressive agents (drugs or radiation) or by lymphocyte depletion or may be specific as in desensitization or the simultaneous administration of antigen and immunosuppressive drugs. [NIH] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunosuppressive Agents: Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of suppressor T-cell populations or by inhibiting the activation of helper cells. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of interleukins and other cytokines are emerging. [NIH] Immunotherapy: Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Implantation: The insertion or grafting into the body of biological, living, inert, or radioactive material. [EU] Impotence: The inability to perform sexual intercourse. [NIH] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH] Incubation: The development of an infectious disease from the entrance of the pathogen to the appearance of clinical symptoms. [EU] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infancy: The period of complete dependency prior to the acquisition of competence in walking, talking, and self-feeding. [NIH] Infantile: Pertaining to an infant or to infancy. [EU] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease.

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[EU]

Infertility: The diminished or absent ability to conceive or produce an offspring while sterility is the complete inability to conceive or produce an offspring. [NIH] Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Ingestion: Taking into the body by mouth [NIH] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Inoperable: Not suitable to be operated upon. [EU] Inorganic: Pertaining to substances not of organic origin. [EU] Inositol: An isomer of glucose that has traditionally been considered to be a B vitamin although it has an uncertain status as a vitamin and a deficiency syndrome has not been identified in man. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1379) Inositol phospholipids are important in signal transduction. [NIH] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Insulator: Material covering the metal conductor of the lead. It is usually polyurethane or silicone. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune, genetic, and environmental factors are involved in the development of type I diabetes. [NIH] Insulin-like: Muscular growth factor. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intestinal: Having to do with the intestines. [NIH] Intestinal Mucosa: The surface lining of the intestines where the cells absorb nutrients. [NIH] Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intramuscular: IM. Within or into muscle. [NIH] Intravenous: IV. Into a vein. [NIH] Involuntary: Reaction occurring without intention or volition. [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] Iris: The most anterior portion of the uveal layer, separating the anterior chamber from the

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posterior. It consists of two layers - the stroma and the pigmented epithelium. Color of the iris depends on the amount of melanin in the stroma on reflection from the pigmented epithelium. [NIH] Islet: Cell producing insulin in pancreas. [NIH] Jejunostomy: Surgical formation of an opening through the abdominal wall into the jejunum, usually for enteral hyperalimentation. [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] Ketoacidosis: Acidosis accompanied by the accumulation of ketone bodies (ketosis) in the body tissues and fluids, as in diabetic acidosis. [EU] Ketone Bodies: Chemicals that the body makes when there is not enough insulin in the blood and it must break down fat for its energy. Ketone bodies can poison and even kill body cells. When the body does not have the help of insulin, the ketones build up in the blood and then "spill" over into the urine so that the body can get rid of them. The body can also rid itself of one type of ketone, called acetone, through the lungs. This gives the breath a fruity odor. Ketones that build up in the body for a long time lead to serious illness and coma. [NIH] Ketosis: A condition of having ketone bodies build up in body tissues and fluids. The signs of ketosis are nausea, vomiting, and stomach pain. Ketosis can lead to ketoacidosis. [NIH] Kidney 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] Kinetics: The study of rate dynamics in chemical or physical systems. [NIH] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Lactation: The period of the secretion of milk. [EU] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Least-Squares Analysis: A principle of estimation in which the estimates of a set of parameters in a statistical model are those quantities minimizing the sum of squared differences between the observed values of a dependent variable and the values predicted by the model. [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] Leptin: A 16-kD peptide hormone secreted from white adipocytes and implicated in the regulation of food intake and energy balance. Leptin provides the key afferent signal from fat cells in the feedback system that controls body fat stores. [NIH] Lesion: An area of abnormal tissue change. [NIH] 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] Libido: The psychic drive or energy associated with sexual instinct in the broad sense (pleasure and love-object seeking). It may also connote the psychic energy associated with instincts in general that motivate behavior. [NIH] Ligaments: Shiny, flexible bands of fibrous tissue connecting together articular extremities of bones. They are pliant, tough, and inextensile. [NIH]

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Ligation: Application of a ligature to tie a vessel or strangulate a part. [NIH] Likelihood Functions: Functions constructed from a statistical model and a set of observed data which give the probability of that data for various values of the unknown model parameters. Those parameter values that maximize the probability are the maximum likelihood estimates of the parameters. [NIH] Linear Models: Statistical models in which the value of a parameter for a given value of a factor is assumed to be equal to a + bx, where a and b are constants. The models predict a linear regression. [NIH] Linkage: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Lipid: Fat. [NIH] Lipid A: Lipid A is the biologically active component of lipopolysaccharides. It shows strong endotoxic activity and exhibits immunogenic properties. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] Lipodystrophy: A collection of rare conditions resulting from defective fat metabolism and characterized by atrophy of the subcutaneous fat. They include total, congenital or acquired, partial, abdominal infantile, and localized lipodystrophy. [NIH] Lipopolysaccharides: Substance consisting of polysaccaride and lipid. [NIH] Lipoprotein: Any of the lipid-protein complexes in which lipids are transported in the blood; lipoprotein particles consist of a spherical hydrophobic core of triglycerides or cholesterol esters surrounded by an amphipathic monolayer of phospholipids, cholesterol, and apolipoproteins; the four principal classes are high-density, low-density, and very-lowdensity lipoproteins and chylomicrons. [EU] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver Cirrhosis: Liver disease in which the normal microcirculation, the gross vascular anatomy, and the hepatic architecture have been variably destroyed and altered with fibrous septa surrounding regenerated or regenerating parenchymal nodules. [NIH] 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] Logistic Models: Statistical models which describe the relationship between a qualitative dependent variable (that is, one which can take only certain discrete values, such as the presence or absence of a disease) and an independent variable. A common application is in epidemiology for estimating an individual's risk (probability of a disease) as a function of a given risk factor. [NIH] Longitudinal study: Also referred to as a "cohort study" or "prospective study"; the analytic method of epidemiologic study in which subsets of a defined population can be identified who are, have been, or in the future may be exposed or not exposed, or exposed in different degrees, to a factor or factors hypothesized to influence the probability of occurrence of a given disease or other outcome. The main feature of this type of study is to observe large numbers of subjects over an extended time, with comparisons of incidence rates in groups that differ in exposure levels. [NIH]

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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] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphoblasts: Interferon produced predominantly by leucocyte cells. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] Lymphocyte Depletion: Immunosuppression by reduction of circulating lymphocytes or by T-cell depletion of bone marrow. The former may be accomplished in vivo by thoracic duct drainage or administration of antilymphocyte serum. The latter is performed ex vivo on bone marrow before its transplantation. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lysosomal Storage Diseases: Inborn errors of metabolism characterized by defects in specific lysosomal hydrolases and resulting in intracellular accumulation of unmetabolized substrates. [NIH] Macrophage: A type of white blood cell that surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system cells. [NIH] Malabsorption: Impaired intestinal absorption of nutrients. [EU] Malignancy: A cancerous tumor that can invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]

Mandible: The largest and strongest bone of the face constituting the lower jaw. It supports the lower teeth. [NIH] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] 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]

Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] Medical Records: Recording of pertinent information concerning patient's illness or illnesses. [NIH] Medicament: A medicinal substance or agent. [EU]

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MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Meiosis: A special method of cell division, occurring in maturation of the germ cells, by means of which each daughter nucleus receives half the number of chromosomes characteristic of the somatic cells of the species. [NIH] Melanin: The substance that gives the skin its color. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Menopause: Permanent cessation of menstruation. [NIH] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH] Mental Retardation: Refers to sub-average general intellectual functioning which originated during the developmental period and is associated with impairment in adaptive behavior. [NIH]

Metabolic acidosis: (met-ah-BOL-ik as-id-O-sis): A condition in which the blood is too acidic. It may be caused by severe illness or sepsis (bacteria in the bloodstream). [NIH] Metabolic Clearance Rate: Volume of biological fluid completely cleared of drug metabolites as measured in unit time. Elimination occurs as a result of metabolic processes in the kidney, liver, saliva, sweat, intestine, heart, brain, or other site. [NIH] Metabolic disorder: A condition in which normal metabolic processes are disrupted, usually because of a missing enzyme. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] 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] 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] Micronutrients: Essential dietary elements or organic compounds that are required in only small quantities for normal physiologic processes to occur. [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] Midaxillary line: An imaginary vertical line that passes midway between the anterior and posterior axillary (armpit) folds. [NIH]

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Millimeter: A measure of length. A millimeter is approximately 26-times smaller than an inch. [NIH] Mineralocorticoids: A group of corticosteroids primarily associated with the regulation of water and electrolyte balance. This is accomplished through the effect on ion transport in renal tubules, resulting in retention of sodium and loss of potassium. Mineralocorticoid secretion is itself regulated by plasma volume, serum potassium, and angiotensin II. [NIH] Minority Groups: A subgroup having special characteristics within a larger group, often bound together by special ties which distinguish it from the larger group. [NIH] Mitochondrial Swelling: Increase in volume of mitochondria due to an influx of fluid; it occurs in hypotonic solutions due to osmotic pressure and in isotonic solutions as a result of altered permeability of the membranes of respiring mitochondria. [NIH] 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] Monoclonal antibodies: Laboratory-produced substances that can locate and bind to cancer cells wherever they are in the body. Many monoclonal antibodies are used in cancer detection or therapy; each one recognizes a different protein on certain cancer cells. Monoclonal antibodies can be used alone, or they can be used to deliver drugs, toxins, or radioactive material directly to a tumor. [NIH] Monocyte: A type of white blood cell. [NIH] Mononuclear: A cell with one nucleus. [NIH] Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Motility: The ability to move spontaneously. [EU] Motor nerve: An efferent nerve conveying an impulse that excites muscular contraction. [NIH]

Mucopolysaccharidoses: Group of lysosomal storage diseases each caused by an inherited deficiency of an enzyme involved in the degradation of glycosaminoglycans (mucopolysaccharides). The diseases are progressive and often display a wide spectrum of clinical severity within one enzyme deficiency. [NIH] Multicenter study: A clinical trial that is carried out at more than one medical institution. [NIH]

Multiple sclerosis: A disorder of the central nervous system marked by weakness, numbness, a loss of muscle coordination, and problems with vision, speech, and bladder control. Multiple sclerosis is thought to be an autoimmune disease in which the body's immune system destroys myelin. Myelin is a substance that contains both protein and fat (lipid) and serves as a nerve insulator and helps in the transmission of nerve signals. [NIH]

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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] Mutagenesis: Process of generating genetic mutations. It may occur spontaneously or be induced by mutagens. [NIH] Mutagens: Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. [NIH] Mydriatic: 1. Dilating the pupil. 2. Any drug that dilates the pupil. [EU] Myelin: The fatty substance that covers and protects nerves. [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] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myotonic Dystrophy: A condition presenting muscle weakness and wasting which may be progressive. [NIH] Nasogastric: The process of passing a small, flexible plastic tube through the nose or mouth into the stomach or small intestine. [NIH] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] 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] Neonatal: Pertaining to the first four weeks after birth. [EU] Neoplasm: A new growth of benign or malignant tissue. [NIH] Nephrogenic: Constant thirst and frequent urination because the kidney tubules cannot respond to antidiuretic hormone. The result is an increase in urine formation and excessive urine flow. [NIH] Nephropathy: Disease of the kidneys. [EU] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neural Pathways: Neural tracts connecting one part of the nervous system with another. [NIH]

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Neuromuscular: Pertaining to muscles and nerves. [EU] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neuropathy: A problem in any part of the nervous system except the brain and spinal cord. Neuropathies can be caused by infection, toxic substances, or disease. [NIH] Neuropeptide: A member of a class of protein-like molecules made in the brain. Neuropeptides consist of short chains of amino acids, with some functioning as neurotransmitters and some functioning as hormones. [NIH] Neurosecretory Systems: A system of neurons that has the specialized function to produce and secrete hormones, and that constitutes, in whole or in part, an endocrine organ or system. [NIH] Neurotransmitter: Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel across the synaptic cleft to either excite or inhibit the target cell. Among the many substances that have the properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic acid, substance P, enkephalins, endorphins, and serotonin. [EU] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] 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] Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the

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next. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nutritional Status: State of the body in relation to the consumption and utilization of nutrients. [NIH] Nutritional Support: The administration of nutrients for assimilation and utilization by a patient by means other than normal eating. It does not include fluid therapy which normalizes body fluids to restore water-electrolyte balance. [NIH] Nutritive Value: An indication of the contribution of a food to the nutrient content of the diet. This value depends on the quantity of a food which is digested and absorbed and the amounts of the essential nutrients (protein, fat, carbohydrate, minerals, vitamins) which it contains. This value can be affected by soil and growing conditions, handling and storage, and processing. [NIH] Observational study: An epidemiologic study that does not involve any intervention, experimental or otherwise. Such a study may be one in which nature is allowed to take its course, with changes in one characteristic being studied in relation to changes in other characteristics. Analytical epidemiologic methods, such as case-control and cohort study designs, are properly called observational epidemiology because the investigator is observing without intervention other than to record, classify, count, and statistically analyze results. [NIH] Obstetrics: A medical-surgical specialty concerned with management and care of women during pregnancy, parturition, and the puerperium. [NIH] Oculomotor: Cranial nerve III. It originate from the lower ventral surface of the midbrain and is classified as a motor nerve. [NIH] Oculomotor Nerve: The 3d cranial nerve. The oculomotor nerve sends motor fibers to the levator muscles of the eyelid and to the superior rectus, inferior rectus, and inferior oblique muscles of the eye. It also sends parasympathetic efferents (via the ciliary ganglion) to the muscles controlling pupillary constriction and accommodation. The motor fibers originate in the oculomotor nuclei of the midbrain. [NIH] Odds Ratio: The ratio of two odds. The exposure-odds ratio for case control data is the ratio of the odds in favor of exposure among cases to the odds in favor of exposure among noncases. The disease-odds ratio for a cohort or cross section is the ratio of the odds in favor of disease among the exposed to the odds in favor of disease among the unexposed. The prevalence-odds ratio refers to an odds ratio derived cross-sectionally from studies of prevalent cases. [NIH] Odour: A volatile emanation that is perceived by the sense of smell. [EU] Oestrogen: A generic term for oestrus-producing steroid compounds; the female sex hormones. In humans, oestrogen is formed in the ovary, possibly the adrenal cortex, the testis, and the foetoplacental unit; it has various functions in both sexes. It is responsible for the development of the female secondary sex characteristics, and during the menstrual cycle it acts on the female genitalia to produce an environment suitable for the fertilization, implantation, and nutrition of the early embryo. Oestrogen is used in oral contraceptives and as a palliative in cancer of the breast after menopause and cancer of the prostate; other uses include the relief of the discomforts of menopause, inhibition of lactation, and treatment of osteoporosis, threatened abortion, and various functional ovarian disorders. [EU]

Oligomenorrhea: Abnormally infrequent menstruation. [NIH] Omega-3 fatty acid: A type of fat obtained in the diet and involved in immunity. [NIH]

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Oncology: The study of cancer. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Optic cup: The white, cup-like area in the center of the optic disc. [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] Osteoclasts: A large multinuclear cell associated with the absorption and removal of bone. An odontoclast, also called cementoclast, is cytomorphologically the same as an osteoclast and is involved in cementum resorption. [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] Ovariectomy: The surgical removal of one or both ovaries. [NIH] Ovaries: The pair of female reproductive glands in which the ova, or eggs, are formed. The ovaries are located in the pelvis, one on each side of the uterus. [NIH] Ovary: Either of the paired glands in the female that produce the female germ cells and secrete some of the female sex hormones. [NIH] Overweight: An excess of body weight but not necessarily body fat; a body mass index of 25 to 29.9 kg/m2. [NIH] Ovulation: The discharge of a secondary oocyte from a ruptured graafian follicle. [NIH] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]

Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). [NIH] Oxygenation: The process of supplying, treating, or mixing with oxygen. No:1245 oxygenation the process of supplying, treating, or mixing with oxygen. [EU] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Palsy: Disease of the peripheral nervous system occurring usually after many years of increased lead absorption. [NIH] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Pancreatic cancer: Cancer of the pancreas, a salivary gland of the abdomen. [NIH] 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

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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] Parathyroid: 1. Situated beside the thyroid gland. 2. One of the parathyroid glands. 3. A sterile preparation of the water-soluble principle(s) of the parathyroid glands, ad-ministered parenterally as an antihypocalcaemic, especially in the treatment of acute hypoparathyroidism with tetany. [EU] Parathyroid Glands: Two small paired endocrine glands in the region of the thyroid gland. They secrete parathyroid hormone and are concerned with the metabolism of calcium and phosphorus. [NIH] Parathyroid hormone: A substance made by the parathyroid gland that helps the body store and use calcium. Also called parathormone, parathyrin, or PTH. [NIH] Parenteral: Not through the alimentary canal but rather by injection through some other route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intravenous, etc. [EU] Parenteral Nutrition: The administering of nutrients for assimilation and utilization by a patient who cannot maintain adequate nutrition by enteral feeding alone. Nutrients are administered by a route other than the alimentary canal (e.g., intravenously, subcutaneously). [NIH] Parity: The number of offspring a female has borne. It is contrasted with gravidity, which refers to the number of pregnancies, regardless of outcome. [NIH] Partial remission: The shrinking, but not complete disappearance, of a tumor in response to therapy. Also called partial response. [NIH] Particle: A tiny mass of material. [EU] Partnership Practice: A voluntary contract between two or more doctors who may or may not share responsibility for the care of patients, with proportional sharing of profits and losses. [NIH] Parturition: The act or process of given birth to a child. [EU] 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] 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]

Pediatrics: A medical specialty concerned with maintaining health and providing medical care to children from birth to adolescence. [NIH] Pelvis: The lower part of the abdomen, located between the hip bones. [NIH] Penicillin: An antibiotic drug used to treat infection. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Perfusion: Bathing an organ or tissue with a fluid. In regional perfusion, a specific area of

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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] Perinatal: Pertaining to or occurring in the period shortly before and after birth; variously defined as beginning with completion of the twentieth to twenty-eighth week of gestation and ending 7 to 28 days after birth. [EU] Perindopril: An angiotensin-converting enzyme inhibitor. It is used in patients with hypertension and heart failure. [NIH] Periodontal disease: Disease involving the supporting structures of the teeth (as the gums and periodontal membranes). [NIH] Periodontal disease: Disease involving the supporting structures of the teeth (as the gums and periodontal membranes). [NIH] Periodontitis: Inflammation of the periodontal membrane; also called periodontitis simplex. [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] Phagocyte: An immune system cell that can surround and kill microorganisms and remove dead cells. Phagocytes include macrophages. [NIH] Pharmaceutic Aids: Substances which are of little or no therapeutic value, but are necessary in the manufacture, compounding, storage, etc., of pharmaceutical preparations or drug dosage forms. They include solvents, diluting agents, and suspending agents, and emulsifying agents. Also, antioxidants; preservatives, pharmaceutical; dyes (coloring agents); flavoring agents; vehicles; excipients; ointment bases. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phlebotomy: The letting of blood from a vein. Although it is one of the techniques used in drawing blood to be used in diagnostic procedures, in modern medicine, it is used commonly in the treatment of erythrocytosis, hemochromocytosis, polycythemia vera, and porphyria cutanea tarda. Its historical counterpart is bloodletting. (From Cecil Textbook of Medicine, 19th ed & Wintrobe's Clinical Hematology, 9th ed) Venipuncture is not only for the letting of blood from a vein but also for the injecting of a drug into the vein for diagnostic analysis. [NIH] Phosphodiesterase: Effector enzyme that regulates the levels of a second messenger, the cyclic GMP. [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

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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] Photosensitivity: An abnormal cutaneous response involving the interaction between photosensitizing substances and sunlight or filtered or artificial light at wavelengths of 280400 mm. There are two main types : photoallergy and photoxicity. [EU] 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] Pilot study: The initial study examining a new method or treatment. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [NIH] 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] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasma protein: One of the hundreds of different proteins present in blood plasma, including carrier proteins ( such albumin, transferrin, and haptoglobin), fibrinogen and other coagulation factors, complement components, immunoglobulins, enzyme inhibitors, precursors of substances such as angiotension and bradykinin, and many other types of proteins. [EU] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Platinum: Platinum. A heavy, soft, whitish metal, resembling tin, atomic number 78, atomic weight 195.09, symbol Pt. (From Dorland, 28th ed) It is used in manufacturing equipment for laboratory and industrial use. It occurs as a black powder (platinum black) and as a spongy substance (spongy platinum) and may have been known in Pliny's time as "alutiae". [NIH]

Pneumonia: Inflammation of the lungs. [NIH] Polycystic: An inherited disorder characterized by many grape-like clusters of fluid-filled cysts that make both kidneys larger over time. These cysts take over and destroy working kidney tissue. PKD may cause chronic renal failure and end-stage renal disease. [NIH] Polycystic Ovary Syndrome: Clinical symptom complex characterized by oligomenorrhea or amenorrhea, anovulation, and regularly associated with bilateral polycystic ovaries. [NIH]

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Polygenic Inheritance: A phenotypic outcome that is determined by more than one gene, such as a variety of physical characteristics or diseases. [NIH] Polymerase: An enzyme which catalyses the synthesis of DNA using a single DNA strand as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH] Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Polyunsaturated fat: An unsaturated fat found in greatest amounts in foods derived from plants, including safflower, sunflower, corn, and soybean oils. [NIH] Porphyria: A group of disorders characterized by the excessive production of porphyrins or their precursors that arises from abnormalities in the regulation of the porphyrin-heme pathway. The porphyrias are usually divided into three broad groups, erythropoietic, hepatic, and erythrohepatic, according to the major sites of abnormal porphyrin synthesis. [NIH]

Porphyria Cutanea Tarda: A form of hepatic porphyria (porphyria, hepatic) characterized by photosensitivity resulting in bullae that rupture easily to form shallow ulcers. This condition occurs in two forms: a sporadic, nonfamilial form that begins in middle age and has normal amounts of uroporphyrinogen decarboxylase with diminished activity in the liver; and a familial form in which there is an autosomal dominant inherited deficiency of uroporphyrinogen decarboxylase in the liver and red blood cells. [NIH] Porphyria, Hepatic: Porphyria in which the liver is the site where excess formation of porphyrin or its precursors is found. Acute intermittent porphyria and porphyria cutanea tarda are types of hepatic porphyria. [NIH] Porphyrins: A group of compounds containing the porphin structure, four pyrrole rings connected by methine bridges in a cyclic configuration to which a variety of side chains are attached. The nature of the side chain is indicated by a prefix, as uroporphyrin, hematoporphyrin, etc. The porphyrins, in combination with iron, form the heme component in biologically significant compounds such as hemoglobin and myoglobin. [NIH] 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] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Potentiate: A degree of synergism which causes the exposure of the organism to a harmful

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substance to worsen a disease already contracted. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Prazosin: A selective adrenergic alpha-1 antagonist used in the treatment of heart failure, hypertension, pheochromocytoma, Raynaud's syndrome, prostatic hypertrophy, and urinary retention. [NIH] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Predisposition: A latent susceptibility to disease which may be activated under certain conditions, as by stress. [EU] Prednisolone: A glucocorticoid with the general properties of the corticosteroids. It is the drug of choice for all conditions in which routine systemic corticosteroid therapy is indicated, except adrenal deficiency states. [NIH] Prednisone: A synthetic anti-inflammatory glucocorticoid derived from cortisone. It is biologically inert and converted to prednisolone in the liver. [NIH] Pre-Eclampsia: Development of hypertension with proteinuria, edema, or both, due to pregnancy or the influence of a recent pregnancy. It occurs after the 20th week of gestation, but it may develop before this time in the presence of trophoblastic disease. [NIH] 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] Pregnancy Tests: Tests to determine whether or not an individual is pregnant. [NIH] Premenopausal: Refers to the time before menopause. Menopause is the time of life when a women's menstrual periods stop permanently; also called "change of life." [NIH] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Primary Prevention: Prevention of disease or mental disorders in susceptible individuals or populations through promotion of health, including mental health, and specific protection, as in immunization, as distinguished from the prevention of complications or after-effects of existing disease. [NIH] Private Practice: Practice of a health profession by an individual, offering services on a person-to-person basis, as opposed to group or partnership practice. [NIH] Probe: An instrument used in exploring cavities, or in the detection and dilatation of strictures, or in demonstrating the potency of channels; an elongated instrument for exploring or sounding body cavities. [NIH] Progeny: The offspring produced in any generation. [NIH] Progesterone: Pregn-4-ene-3,20-dione. The principal progestational hormone of the body, secreted by the corpus luteum, adrenal cortex, and placenta. Its chief function is to prepare the uterus for the reception and development of the fertilized ovum. It acts as an

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antiovulatory agent when administered on days 5-25 of the menstrual cycle. [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Proinsulin: The substance made first in the pancreas that is then made into insulin. When insulin is purified from the pancreas of pork or beef, all the proinsulin is not fully removed. When some people use these insulins, the proinsulin can cause the body to react with a rash, to resist the insulin, or even to make dents or lumps in the skin at the place where the insulin is injected. The purified insulins have less proinsulin and other impurities than the other types of insulins. [NIH] Proline: A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. [NIH] Prone: Having the front portion of the body downwards. [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] 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] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protease Inhibitors: Compounds which inhibit or antagonize biosynthesis or actions of proteases (endopeptidases). [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 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] Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or

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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] Pruritus: An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. [NIH] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Puberty: The period during which the secondary sex characteristics begin to develop and the capability of sexual reproduction is attained. [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]

Puerperium: Period from delivery of the placenta until return of the reproductive organs to their normal nonpregnant morphologic state. In humans, the puerperium generally lasts for six to eight weeks. [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] 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]

Purified Insulins: Insulins with much less of the impure proinsulin. It is thought that the use of purified insulins may help avoid or reduce some of the problems of people with diabetes such as allergic reactions. [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] Pyrimidines: A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (cytosine, thymine, and uracil) and form the basic structure of the barbiturates. [NIH] Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the

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waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radioactive: Giving off radiation. [NIH] Radiography: Examination of any part of the body for diagnostic purposes by means of roentgen rays, recording the image on a sensitized surface (such as photographic film). [NIH] Random Allocation: A process involving chance used in therapeutic trials or other research endeavor for allocating experimental subjects, human or animal, between treatment and control groups, or among treatment groups. It may also apply to experiments on inanimate objects. [NIH] Randomization: Also called random allocation. Is allocation of individuals to groups, e.g., for experimental and control regimens, by chance. Within the limits of chance variation, random allocation should make the control and experimental groups similar at the start of an investigation and ensure that personal judgment and prejudices of the investigator do not influence allocation. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Randomized clinical trial: A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be in a randomized trial. [NIH] Reabsorption: 1. The act or process of absorbing again, as the selective absorption by the kidneys of substances (glucose, proteins, sodium, etc.) already secreted into the renal tubules, and their return to the circulating blood. 2. Resorption. [EU] 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] 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] 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] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Regression Analysis: Procedures for finding the mathematical function which best describes the relationship between a dependent variable and one or more independent variables. In linear regression (see linear models) the relationship is constrained to be a straight line and least-squares analysis is used to determine the best fit. In logistic regression (see logistic models) the dependent variable is qualitative rather than continuously variable and likelihood functions are used to find the best relationship. In multiple regression the

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dependent variable is considered to depend on more than a single independent variable. [NIH]

Rehydration: The restoration of water or of fluid content to a body or to substance which has become dehydrated. [EU] Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Renal failure: Progressive renal insufficiency and uremia, due to irreversible and progressive renal glomerular tubular or interstitial disease. [NIH] Reproduction Techniques: Methods pertaining to the generation of new individuals. [NIH] Research Support: Financial support of research activities. [NIH] Resection: Removal of tissue or part or all of an organ by surgery. [NIH] Resorption: The loss of substance through physiologic or pathologic means, such as loss of dentin and cementum of a tooth, or of the alveolar process of the mandible or maxilla. [EU] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Resting metabolic rate: RMR accounts for 65 to 75 percent of daily energy expenditure and represents the minimum energy needed to maintain all physiological cell functions in the resting state. The principal determinant of RMR is lean body mass (LBM). Obese subjects have a higher RMR in absolute terms than lean individuals, an equivalent RMR when corrected for LBM and per unit surface area, and a lower RMR when expressed per kilogram of body weight. Obese persons require more energy for any given activity because of a larger mass, but they tend to be more sedentary than lean subjects. [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] Retinopathy: 1. Retinitis (= inflammation of the retina). 2. Retinosis (= degenerative, noninflammatory condition of the retina). [EU] Retrospective: Looking back at events that have already taken place. [NIH] Retrospective study: A study that looks backward in time, usually using medical records and interviews with patients who already have or had a disease. [NIH] Reverse Transcriptase Inhibitors: Inhibitors of reverse transcriptase (RNA-directed DNA polymerase), an enzyme that synthesizes DNA on an RNA template. [NIH] Rheumatism: A group of disorders marked by inflammation or pain in the connective tissue

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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] Ribosome: A granule of protein and RNA, synthesized in the nucleolus and found in the cytoplasm of cells. Ribosomes are the main sites of protein synthesis. Messenger RNA attaches to them and there receives molecules of transfer RNA bearing amino acids. [NIH] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Risk patient: Patient who is at risk, because of his/her behaviour or because of the type of person he/she is. [EU] Rod: A reception for vision, located in the retina. [NIH] 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] 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] Saturated fat: A type of fat found in greatest amounts in foods from animals, such as fatty cuts of meat, poultry with the skin, whole-milk dairy products, lard, and in some vegetable oils, including coconut, palm kernel, and palm oils. Saturated fat raises blood cholesterol more than anything else eaten. On a Step I Diet, no more than 8 to 10 percent of total calories should come from saturated fat, and in the Step II Diet, less than 7 percent of the day's total calories should come from saturated fat. [NIH] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Sebaceous: Gland that secretes sebum. [NIH] Sebaceous gland: Gland that secretes sebum. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Secretory: Secreting; relating to or influencing secretion or the secretions. [NIH] 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] Selenium: An element with the atomic symbol Se, atomic number 34, and atomic weight 78.96. It is an essential micronutrient for mammals and other animals but is toxic in large amounts. Selenium protects intracellular structures against oxidative damage. It is an essential component of glutathione peroxidase. [NIH] Senescence: The bodily and mental state associated with advancing age. [NIH]

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Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [NIH] Sepsis: The presence of bacteria in the bloodstream. [NIH] Septic: Produced by or due to decomposition by microorganisms; putrefactive. [EU] 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] Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (receptors, serotonin) explain the broad physiological actions and distribution of this biochemical mediator. [NIH] Serous: Having to do with serum, the clear liquid part of blood. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Sex Characteristics: Those characteristics that distinguish one sex from the other. The primary sex characteristics are the ovaries and testes and their related hormones. Secondary sex characteristics are those which are masculine or feminine but not directly related to reproduction. [NIH] 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] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Silicon: A trace element that constitutes about 27.6% of the earth's crust in the form of silicon dioxide. It does not occur free in nature. Silicon has the atomic symbol Si, atomic number 14, and atomic weight 28.09. [NIH] Silicon Dioxide: Silica. Transparent, tasteless crystals found in nature as agate, amethyst, chalcedony, cristobalite, flint, sand, quartz, and tridymite. The compound is insoluble in water or acids except hydrofluoric acid. [NIH] Sirolimus: A macrolide compound obtained from Streptomyces hygroscopicus that acts by selectively blocking the transcriptional activation of cytokines thereby inhibiting cytokine production. It is bioactive only when bound to immunophilins. Sirolimus is a potent immunosuppressant and possesses both antifungal and antineoplastic properties. [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] 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

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absence of respiratory effort. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [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] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Somatostatin: A polypeptide hormone produced in the hypothalamus, and other tissues and organs. It inhibits the release of human growth hormone, and also modulates important physiological functions of the kidney, pancreas, and gastrointestinal tract. Somatostatin receptors are widely expressed throughout the body. Somatostatin also acts as a neurotransmitter in the central and peripheral nervous systems. [NIH] Soybean Oil: Oil from soybean or soybean plant. [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] Sperm: The fecundating fluid of the male. [NIH] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spirochete: Lyme disease. [NIH] Spleen: An organ that is part of the lymphatic system. The spleen produces lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side of the abdomen near the stomach. [NIH] 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

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manner. [EU] Sprue: A non febrile tropical disease of uncertain origin. [NIH] Steatosis: Fatty degeneration. [EU] Steel: A tough, malleable, iron-based alloy containing up to, but no more than, two percent carbon and often other metals. It is used in medicine and dentistry in implants and instrumentation. [NIH] Stem Cells: Relatively undifferentiated cells of the same lineage (family type) that retain the ability to divide and cycle throughout postnatal life to provide cells that can become specialized and take the place of those that die or are lost. [NIH] Sterile: Unable to produce children. [NIH] Sterility: 1. The inability to produce offspring, i.e., the inability to conceive (female s.) or to induce conception (male s.). 2. The state of being aseptic, or free from microorganisms. [EU] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Stillbirth: The birth of a dead fetus or baby. [NIH] Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subcutaneous: Beneath the skin. [NIH] 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] 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] Sweat: The fluid excreted by the sweat glands. It consists of water containing sodium

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chloride, phosphate, urea, ammonia, and other waste products. [NIH] Sympathetic Nervous System: The thoracolumbar division of the autonomic nervous system. Sympathetic preganglionic fibers originate in neurons of the intermediolateral column of the spinal cord and project to the paravertebral and prevertebral ganglia, which in turn project to target organs. The sympathetic nervous system mediates the body's response to stressful situations, i.e., the fight or flight reactions. It often acts reciprocally to the parasympathetic system. [NIH] Sympathomimetic: 1. Mimicking the effects of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. 2. An agent that produces effects similar to those of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. Called also adrenergic. [EU] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Synapse: The region where the processes of two neurons come into close contiguity, and the nervous impulse passes from one to the other; the fibers of the two are intermeshed, but, according to the general view, there is no direct contiguity. [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] Syphilis: A contagious venereal disease caused by the spirochete Treponema pallidum. [NIH]

Systemic: Affecting the entire body. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Tacrolimus: A macrolide isolated from the culture broth of a strain of Streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro. [NIH] Telomerase: Essential ribonucleoprotein reverse transcriptase that adds telomeric DNA to the ends of eukaryotic chromosomes. Telomerase appears to be repressed in normal human somatic tissues but reactivated in cancer, and thus may be necessary for malignant transformation. EC 2.7.7.-. [NIH] Telomere: A terminal section of a chromosome which has a specialized structure and which is involved in chromosomal replication and stability. Its length is believed to be a few hundred base pairs. [NIH] Terbutaline: A selective beta-2 adrenergic agonist used as a bronchodilator and tocolytic. [NIH]

Testis: Either of the paired male reproductive glands that produce the male germ cells and the male hormones. [NIH] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] Tetany: 1. Hyperexcitability of nerves and muscles due to decrease in concentration of extracellular ionized calcium, which may be associated with such conditions as parathyroid hypofunction, vitamin D deficiency, and alkalosis or result from ingestion of alkaline salts; it is characterized by carpopedal spasm, muscular twitching and cramps, laryngospasm with inspiratory stridor, hyperreflexia and choreiform movements. 2. Tetanus. [EU] Therapeutics: The branch of medicine which is concerned with the treatment of diseases,

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palliative or curative. [NIH] Thinness: A state of insufficient flesh on the body usually defined as having a body weight less than skeletal and physical standards. [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] Thrombocytes: Blood cells that help prevent bleeding by causing blood clots to form. Also called platelets. [NIH] Thrombosis: The formation or presence of a blood clot inside a blood vessel. [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] Thyrotoxicosis: The clinical syndrome that reflects the response of the peripheral tissues to an excess of thyroid hormone. [NIH] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tocolysis: Any drug treatment modality designed to inhibit uterine contractions in pregnant women at risk for preterm labor. [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] 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] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxin: A poison; frequently used to refer specifically to a protein produced by some higher plants, certain animals, and pathogenic bacteria, which is highly toxic for other living organisms. Such substances are differentiated from the simple chemical poisons and the vegetable alkaloids by their high molecular weight and antigenicity. [EU] Trace element: Substance or element essential to plant or animal life, but present in extremely small amounts. [NIH] Trachea: The cartilaginous and membranous tube descending from the larynx and

Dictionary 205

branching into the right and left main bronchi. [NIH] Traction: The act of pulling. [NIH] Transcriptase: An enzyme which catalyses the synthesis of a complementary mRNA molecule from a DNA template in the presence of a mixture of the four ribonucleotides (ATP, UTP, GTP and CTP). [NIH] Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. [NIH] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] Translocation: The movement of material in solution inside the body of the plant. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] 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] Triglyceride: A lipid carried through the blood stream to tissues. Most of the body's fat tissue is in the form of triglycerides, stored for use as energy. Triglycerides are obtained primarily from fat in foods. [NIH] Troglitazone: A drug used in diabetes treatment that is being studied for its effect on reducing the risk of cancer cell growth in fat tissue. [NIH] Trophic: Of or pertaining to nutrition. [EU] Truncal: The bilateral dissection of the abdominal branches of the vagus nerve. [NIH] Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Tumor marker: A substance sometimes found in an increased amount in the blood, other body fluids, or tissues and which may mean that a certain type of cancer is in the body. Examples of tumor markers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and gastrointestinal tract cancers), and PSA (prostate cancer). Also called biomarker. [NIH] 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] 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]

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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] 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] 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] 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] Uroporphyrinogen Decarboxylase: One of the enzymes active in heme biosynthesis. It catalyzes the decarboxylation of uroporphyrinogen III to coproporphyrinogen III by the conversion of four acetic acid groups to four methyl groups. EC 4.1.1.37. [NIH] 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] 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] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasculitis: Inflammation of a blood vessel. [NIH] Vasoconstriction: Narrowing of the blood vessels without anatomic change, for which constriction, pathologic is used. [NIH] Vasodilator: An agent that widens blood vessels. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH]

Dictionary 207

Venereal: Pertaining or related to or transmitted by sexual contact. [EU] Venous: Of or pertaining to the veins. [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] 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] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Villous: Of a surface, covered with villi. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Viral Hepatitis: Hepatitis caused by a virus. Five different viruses (A, B, C, D, and E) most commonly cause this form of hepatitis. Other rare viruses may also cause hepatitis. [NIH] Virilism: Development of masculine traits in the female. [NIH] Virilization: The induction or development of male secondary sec characters, especially the induction of such changes in the female, including enlargement of the clitoris, growth of facial and body hair, development of a hairline typical of the male forehead, stimulation of secretion and proliferation of the sebaceous glands (often with acne), and deepening of the voice. Called also masculinization) [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] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] Vitamin A: A substance used in cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Vitreous: Glasslike or hyaline; often used alone to designate the vitreous body of the eye (corpus vitreum). [EU] 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] Waist circumference: To define the level at which the waist circumference is measured, a bony landmark is first located and marked. The subject stands, and the technician, positioned to the right of the subject, palpates the upper hip bone to locate the right ileum.

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Just above the uppermost lateral border of the right ileum, a horizontal mark is drawn and then crossed with a vertical mark on the midaxillary line. The measuring tape is then placed around the trunk, at the level of the mark on the right side, making sure that it is on a level horizontal plane on all sides. The tape is then tightened slightly without compressing the skin and underlying subcutaneous tissues. The measure is recorded in centimeters to the nearest millimeter. [NIH] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]

Windpipe: A rigid tube, 10 cm long, extending from the cricoid cartilage to the upper border of the fifth thoracic vertebra. [NIH] 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] Yohimbine: A plant alkaloid with alpha-2-adrenergic blocking activity. Yohimbine has been used as a mydriatic and in the treatment of impotence. It is also alleged to be an aphrodisiac. [NIH]

209

INDEX A Abdomen, 151, 169, 180, 182, 189, 190, 201, 202, 204, 206 Abdominal, 3, 29, 49, 54, 151, 152, 159, 181, 182, 189, 190, 205 Abdominal fat, 3, 151 Abortion, 151, 188, 194 Acceptor, 151, 182, 189 Accommodation, 151, 188 Acculturation, 49, 151 Acetylcholine, 151, 187 Acidosis, 121, 151, 181 Acne, 151, 207 Acute lymphoblastic leukemia, 29, 151 Acute lymphocytic leukemia, 151 Acyl, 110, 151 Adaptation, 69, 151 Adenoma, 109, 152 Adenovirus, 24, 152 Adipocytes, 17, 22, 24, 32, 35, 36, 43, 97, 102, 152, 181 Adipose Tissue, 17, 21, 24, 32, 36, 51, 60, 69, 102, 151, 152 Adjustment, 121, 151, 152 Adjuvant, 30, 152 Adolescence, 9, 152, 190 Adrenal Cortex, 152, 155, 164, 165, 177, 188, 194 Adrenal Glands, 152, 154 Adrenal insufficiency, 8, 152 Adrenal Medulla, 152, 169, 187 Adrenergic, 31, 52, 90, 152, 156, 169, 194, 203, 208 Adrenergic beta-Antagonists, 152, 156 Adverse Effect, 15, 30, 152, 200 Aerobic, 28, 37, 152, 170 Aerobic Exercise, 28, 37, 152 Aetiology, 101, 152 Afferent, 152, 181 Affinity, 152, 153, 201 Age Factors, 4, 153 Age of Onset, 153, 205 Agenesis, 42, 153 Agonist, 153, 203 Airway, 153, 159, 200 Albumin, 39, 153, 192 Algorithms, 153, 158 Alimentary, 153, 166, 169, 190

Alkaline, 151, 153, 159, 203 Alkaloid, 153, 208 Alleles, 11, 38, 153, 176 Allergen, 153, 165 Allogeneic, 35, 153 Allograft, 25, 153 Alopecia, 44, 153 Alpha Particles, 153, 197 Alpha-1, 153, 194 Alternative medicine, 126, 153 Aluminum, 118, 154 Alveolar Process, 154, 198 Ameliorated, 7, 154 Amenorrhea, 154, 192 Amino Acid Sequence, 154, 155 Amniotic Fluid, 154, 173 Ampulla, 154, 161 Amyloid, 78, 154, 175 Amyloidosis, 117, 154 Anaesthesia, 154, 179 Anal, 154, 169, 182 Anaphylatoxins, 154, 163 Anatomical, 154, 161, 179, 199 Androgenic, 26, 154, 155 Androgens, 8, 22, 26, 152, 154, 164, 177 Androstenedione, 26, 155 Anemia, 4, 38, 118, 155 Anesthetics, 155, 169 Angina, 70, 152, 155 Angiotensin-Converting Enzyme Inhibitors, 155, 156 Animal model, 13, 14, 24, 46, 116, 155 Anions, 153, 155, 180 Aniridia, 79, 155 Anorexia, 78, 155, 206 Anovulation, 22, 61, 155, 192 Antagonism, 42, 94, 155 Antiallergic, 155, 164 Antibacterial, 155, 201 Antibiotic, 155, 190, 201 Antibodies, 36, 52, 66, 155, 157, 183, 185, 192 Antibody, 5, 25, 36, 153, 155, 156, 163, 177, 178, 179, 183, 185, 201 Antidiuretic, 156, 186 Antifungal, 156, 200 Antigen, 152, 155, 156, 163, 177, 178, 179, 183

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Antigen-Antibody Complex, 156, 163 Antihypertensive, 5, 75, 76, 77, 90, 98, 156 Antihypertensive Agents, 90, 156 Anti-infective, 156, 171 Anti-Infective Agents, 156, 171 Anti-inflammatory, 156, 164, 166, 174, 194 Anti-Inflammatory Agents, 156, 164 Antineoplastic, 156, 164, 200 Antioxidant, 156, 189 Aplastic anemia, 63, 156 Apnea, 15, 156 Apolipoproteins, 156, 182 Arginine, 87, 154, 156, 187 Arterial, 156, 157, 161, 178, 195, 203 Arteries, 156, 158, 164, 183, 184, 186 Arterioles, 156, 158, 159, 184, 186 Arteriosclerosis, 82, 156, 178, 186 Arteriovenous, 121, 157, 184 Artery, 28, 34, 43, 70, 71, 86, 156, 157, 164, 196 Aspiration, 119, 157 Assay, 85, 157 Asymptomatic, 14, 33, 157, 189 Atrophy, 157, 182 Attenuated, 12, 157 Attenuation, 9, 12, 157 Aural, 58, 157 Autoantibodies, 52, 95, 157 Autoantigens, 157 Autodigestion, 157, 189 Autoimmune disease, 157, 185 Autologous, 100, 157 Autologous bone marrow transplantation, 100, 157 Autosuggestion, 157, 178 Azotemia, 157, 206 B Bacteria, 151, 155, 156, 157, 158, 169, 170, 171, 184, 200, 201, 204, 205 Bacterial Physiology, 151, 157 Bactericidal, 157, 170 Bacteriophage, 157, 205 Benign, 152, 157, 160, 172, 186 Beta-pleated, 154, 157 Bilateral, 157, 192, 205 Bile, 12, 157, 158, 165, 172, 176, 182, 202 Bile Acids, 12, 157, 202 Bile Acids and Salts, 157 Bile duct, 158 Biliary, 117, 158, 161, 163, 176, 190 Biliary Tract, 158, 190 Bilirubin, 153, 158

Biochemical, 31, 61, 118, 153, 158, 200 Biological therapy, 158, 175 Biomarkers, 13, 46, 158 Biopsy, 25, 32, 158 Biosynthesis, 22, 158, 195, 200, 206 Biotechnology, 47, 48, 126, 133, 158 Bladder, 158, 172, 185, 195, 206 Blood Coagulation, 158, 159 Blood Glucose, 14, 21, 55, 60, 83, 110, 111, 119, 121, 158, 176, 178, 180 Blood Platelets, 158, 200 Blood pressure, 4, 9, 50, 76, 82, 86, 156, 158, 160, 172, 178, 185, 201 Blood urea, 121, 158 Blood vessel, 158, 159, 160, 161, 162, 168, 174, 191, 201, 202, 204, 206 Body Composition, 4, 5, 28, 37, 40, 158 Body Fluids, 158, 159, 167, 171, 188, 201, 205 Body Mass Index, 9, 50, 59, 91, 95, 99, 159, 189 Bone Marrow, 43, 100, 151, 156, 157, 159, 165, 173, 178, 183 Bone Marrow Transplantation, 43, 100, 159 Bone Resorption, 38, 159 Bradykinin, 159, 187, 192 Breeding, 47, 159 Bronchi, 159, 169, 205 Bronchodilator, 159, 203 Bypass, 117, 159 C Caesarean section, 18, 159 Calcium, 8, 12, 156, 159, 163, 190, 203 Calcium channel blocker, 156, 159 Calcium Channel Blockers, 156, 159 Calcium Channels, 8, 159 Caloric intake, 121, 159 Capillary, 49, 90, 159, 207 Carcinogenic, 160, 180, 202 Carcinogens, 160, 161 Carcinoid, 65, 160 Carcinoma, 109, 160 Cardiac, 30, 39, 48, 69, 84, 116, 152, 160, 164, 165, 169, 174, 176, 186, 202 Cardiorespiratory, 152, 160 Cardiovascular disease, 4, 9, 10, 15, 27, 29, 77, 81, 88, 114, 116, 118, 160 Carnitine, 108, 160 Case report, 100, 160 Cataract, 44, 85, 160 Catecholamines, 53, 103, 152, 160

211

Catheters, 29, 160 Causal, 15, 23, 160, 169 Cause of Death, 11, 160 Celiac Disease, 139, 160, 173 Cell Cycle, 160, 162 Cell Differentiation, 36, 160 Cell Division, 157, 160, 161, 175, 184, 192, 195 Cell membrane, 22, 159, 161, 191 Cell Survival, 161, 175 Central Nervous System, 29, 151, 159, 161, 172, 185, 200 Cerebral, 161, 169, 170 Cerebrovascular, 113, 159, 160, 161 Cerebrum, 161 Character, 161, 165, 174 Chemotactic Factors, 161, 163 Chemotaxis, 76, 161 Chemotherapy, 29, 161 Chin, 84, 161, 184 Cholestasis, 12, 161 Cholesterol, 7, 9, 10, 62, 103, 108, 109, 157, 158, 161, 162, 164, 167, 177, 182, 183, 199, 202 Cholesterol Esters, 62, 161, 182 Chromaffin System, 161, 168 Chromium, 96, 99, 101, 103, 108, 118, 161 Chromosomal, 44, 161, 203 Chromosome, 16, 49, 161, 182, 203 Chronic Disease, 38, 118, 162 Chronic renal, 4, 48, 54, 76, 86, 116, 121, 162, 192, 206 Chylomicrons, 162, 182 Ciliary, 162, 188 Circadian, 29, 162 Circadian Rhythm, 29, 162 Circulatory system, 162, 168 Cirrhosis, 11, 13, 86, 97, 117, 162, 176 Cisplatin, 103, 162 Clamp, 6, 14, 37, 162 Clinical Medicine, 86, 162, 194 Clinical trial, 8, 30, 33, 39, 133, 162, 164, 165, 185, 195, 197 Clone, 11, 162 Cloning, 158, 162 Cohort Studies, 30, 162, 169 Collagen, 47, 154, 162, 171, 192, 195 Collapse, 163, 200 Colloidal, 153, 163 Common Bile Duct, 12, 163, 165 Complement, 9, 154, 163, 192

Complementary and alternative medicine, 97, 104, 163 Complementary medicine, 97, 163 Computational Biology, 133, 163 Conception, 151, 163, 164, 171, 194, 202 Concomitant, 46, 163 Confusion, 163, 206 Congestive heart failure, 39, 164 Connective Tissue, 159, 162, 164, 171, 198 Constipation, 119, 164 Constitutional, 83, 164 Constriction, 164, 188, 206 Consultation, 13, 39, 46, 57, 164 Contraceptive, 49, 78, 119, 164 Contraindications, ii, 164 Control group, 7, 33, 164, 197 Coordination, 164, 185 Coronary, 7, 23, 28, 30, 34, 43, 70, 71, 75, 82, 160, 164, 184, 186 Coronary Disease, 30, 164 Coronary heart disease, 7, 23, 75, 160, 164 Coronary Thrombosis, 164, 184, 186 Coronary Vessels, 164 Corticosteroid, 87, 164, 194 Cortisol, 8, 15, 40, 49, 56, 153, 165 Cortisone, 165, 166, 194 Cranial, 29, 165, 188, 191, 206 Creatinine, 165, 206 Cultured cells, 32, 165 Curative, 165, 204 Cyclic, 110, 165, 175, 187, 191, 193 Cyclosporine, 25, 165, 179 Cystic Duct, 163, 165 Cytokine, 165, 200 Cytoplasm, 161, 165, 169, 199 Cytotoxicity, 162, 165 D Dairy Products, 165, 199 Data Collection, 18, 20, 39, 165 Decompensation, 18, 19, 165 Degenerative, 165, 176, 198 Deletion, 82, 165 Delivery of Health Care, 165, 173 Demography, 34, 165 Density, 9, 77, 109, 159, 165, 167, 182, 189 Desensitization, 23, 165, 179 Deuterium, 166, 177 Developed Countries, 166, 171 Developing Countries, 6, 166 Dexamethasone, 103, 166 Diabetes Insipidus, 73, 166 Diabetic Foot, 114, 166

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Diabetic Retinopathy, 113, 114, 166 Diagnostic procedure, 107, 126, 166, 191 Dialyzer, 166, 176 Diarrhea, 101, 119, 166 Diarrhoea, 54, 166 Diastole, 166 Diastolic, 84, 166, 178 Dietary Fiber, 108, 166 Dietetics, 120, 121, 166 Digestion, 153, 157, 158, 166, 180, 182, 202 Digestive system, 166, 172 Direct, iii, 16, 19, 23, 162, 166, 197, 203 Discrete, 166, 173, 182 Disease Susceptibility, 11, 119, 167 Disinfectant, 167, 170 Disposition, 28, 167 Dissection, 167, 205 Diuretic, 64, 68, 75, 167 Diuretics, Thiazide, 156, 167 Dose-dependent, 35, 167 Drive, ii, vi, 8, 9, 12, 38, 45, 93, 120, 167, 181 Drug Interactions, 167 Drug Tolerance, 167, 204 Duct, 154, 163, 167, 170, 183, 199 Duodenum, 157, 167, 202 Dyes, 154, 167, 171, 191 Dyslipidemia, 3, 9, 23, 25, 29, 34, 59, 71, 82, 101, 167 Dyspnea, 165, 167 Dystrophic, 117, 167 E Edema, 165, 166, 167, 194, 206 Educational Status, 82, 167 Effector, 42, 151, 163, 167, 191 Efficacy, 26, 33, 37, 39, 114, 167 Elastic, 167, 174 Elastin, 162, 168 Electrolysis, 61, 155, 168 Electrolyte, 121, 164, 168, 171, 176, 185, 188, 193, 201, 206 Electrons, 156, 168, 180, 189, 197 Embryo, 151, 161, 168, 179, 188, 194, 201 Embryo Transfer, 168, 194 Enalapril, 76, 168 Encephalopathy, 118, 168 Endemic, 168, 201 Endocrine Glands, 168, 190 Endocrine System, 98, 168 Endocrinology, 12, 45, 49, 50, 53, 56, 61, 63, 65, 84, 89, 100, 103, 168

Endogenous, 16, 29, 41, 44, 100, 157, 168, 205 Endopeptidases, 168, 195 Endothelial cell, 46, 168 Endothelium, 41, 168, 169, 187 Endothelium, Lymphatic, 168 Endothelium, Vascular, 168, 169 Endothelium-derived, 169, 187 Endotoxic, 169, 182 Endotoxins, 163, 169 End-stage renal, 162, 169, 192 Energy balance, 169, 181 Enteral Nutrition, 108, 119, 169 Environmental Health, 132, 134, 169 Enzymatic, 41, 154, 159, 163, 169, 171, 198 Epidemic, 4, 6, 11, 15, 16, 34, 56, 169, 201 Epidemiologic Studies, 169, 173 Epidemiological, 6, 13, 22, 25, 40, 46, 59, 114, 169 Epigastric, 169, 189 Epinephrine, 31, 47, 75, 152, 169, 187, 205 Epithelial, 152, 169 Epithelial Cells, 169 Epithelium, 168, 169, 181 Erythrocytes, 155, 159, 169, 197 Esophagus, 166, 169, 172, 202 Estrogen, 102, 170 Estrogen receptor, 102, 170 Ethanol, 22, 170 Ethnic Groups, 6, 11, 26, 33, 114, 170 Evacuation, 164, 170 Evoke, 170, 202 Excipients, 170, 171, 191 Exercise Test, 170 Exercise Tolerance, 4, 170 Exhaustion, 155, 170 Exocrine, 170, 189 Exogenous, 40, 168, 170, 205 Extracellular, 154, 164, 170, 171, 201, 203 Extracellular Matrix, 164, 170, 171 Extracorporeal, 118, 170, 176 Eye Infections, 152, 170 F Facial, 170, 207 Faecal, 166, 170 Family Planning, 119, 133, 170 Fatty Liver, 52, 84, 117, 170 Febrile, 171, 202 Feces, 164, 170, 171 Ferritin, 52, 171 Fertilization in Vitro, 171, 194 Fetus, 18, 19, 27, 40, 151, 171, 201, 202, 206

213

Fibrinolysis, 70, 171 Fibroblasts, 44, 171 Fibrosis, 13, 46, 52, 66, 75, 79, 84, 89, 100, 117, 171, 199 Filtration, 121, 171 Flavoring Agents, 171, 191 Fluid Therapy, 171, 188 Fluoxetine, 73, 171 Fold, 19, 33, 171 Food Additives, 139, 171 Food Coloring Agents, 171 Food Preservatives, 171 Foot Care, 113, 171 Foot Ulcer, 166, 171 Forearm, 158, 171 Free Radicals, 111, 156, 171 Fructosamine, 74, 172 Fructose Intolerance, 117, 172 Fundus, 39, 172 G Galactosemia, 117, 172 Gallbladder, 151, 158, 165, 166, 172 Ganglion, 172, 188 Ganglionic Blockers, 156, 172 Gas, 172, 177, 187, 202 Gastric, 69, 157, 160, 172 Gastric Inhibitory Polypeptide, 69, 172 Gastrin, 103, 172, 177 Gastroenterology, 12, 45, 82, 101, 172 Gastrointestinal, 103, 119, 159, 160, 169, 170, 172, 200, 201, 202, 205 Gastrointestinal tract, 119, 170, 172, 200, 201, 205 Gastrostomy, 169, 172 Gene, 10, 13, 21, 24, 35, 36, 37, 42, 46, 51, 82, 83, 84, 152, 153, 158, 173, 177, 193 Gene Expression, 24, 173 Gene Therapy, 152, 173 Genetic Counseling, 119, 173 Genetics, 11, 38, 44, 83, 87, 173 Genotype, 38, 56, 114, 173, 191 Geographic Locations, 114, 173 Geriatric, 59, 120, 173 Germ Cells, 173, 184, 189, 203 Gestation, 5, 18, 20, 50, 58, 173, 191, 194, 201 Gestational Age, 6, 173 Gingivitis, 42, 173 Gland, 152, 161, 165, 173, 177, 189, 190, 192, 195, 199, 202, 204 Gliadin, 139, 173 Glipizide, 33, 173

Glomerular, 173, 198 Glomeruli, 173, 174 Glomerulosclerosis, 57, 76, 77, 174 Glomerulus, 173, 174 Glucocorticoid, 8, 166, 174, 194 Gluconeogenesis, 31, 172, 174 Glucose Tolerance Test, 5, 6, 14, 17, 26, 39, 55, 61, 90, 114, 118, 174 Glucuronic Acid, 174, 176 Glutamate, 95, 139, 174 Glutathione Peroxidase, 174, 199 Gluten, 138, 139, 160, 173, 174 Glycine, 154, 158, 174, 187, 200 Glycogen, 16, 21, 24, 31, 73, 83, 89, 117, 174 Glycogen Storage Disease, 117, 174 Glycogen Synthase, 21, 73, 174 Glycolysis, 31, 174 Glycoproteins, 159, 174 Glycosaminoglycans, 175, 185 Glycosuria, 110, 175 Gonad, 175 Gonadal, 26, 175, 202 Governing Board, 175, 194 Graft, 25, 175, 179 Graft Survival, 25, 175 Gravidity, 175, 190 Growth factors, 40, 47, 175 Guanylate Cyclase, 175, 187 H Habitual, 6, 59, 161, 175 Hawaii, 94, 145, 175 Health Behavior, 12, 30, 45, 175 Health Services, 6, 118, 165, 175 Health Status, 175 Heart attack, 160, 175 Heart failure, 155, 175, 191, 194 Heme, 158, 176, 193, 206 Hemochromatosis, 13, 176 Hemodialysis, 51, 73, 86, 166, 176, 205 Hemofiltration, 121, 176, 205 Hemoglobin, 39, 54, 66, 83, 155, 169, 176, 193 Hemorrhage, 176, 202, 207 Hemostasis, 176, 200 Heparin, 60, 176 Hepatic, 12, 14, 16, 27, 44, 66, 79, 83, 97, 117, 119, 153, 163, 172, 174, 176, 182, 193 Hepatitis, 85, 176, 207 Hepatobiliary, 12, 117, 176 Hepatocellular, 117, 176 Hepatocyte, 161, 176

214

Glucose Intolerance

Hepatology, 12, 45, 176 Hereditary, 41, 49, 117, 155, 176 Heredity, 9, 173, 176 Heterogeneity, 63, 114, 153, 176 Heterozygotes, 42, 176 Hirsutism, 177 Histology, 117, 177 Homeobox, 42, 177 Homeostasis, 15, 17, 20, 22, 32, 36, 42, 177 Homogeneous, 85, 177 Homologous, 153, 173, 176, 177, 203 Homozygotes, 13, 42, 177 Hormonal, 4, 21, 34, 40, 87, 121, 157, 164, 177 Hybrid, 162, 177 Hydrogen, 110, 151, 160, 166, 174, 177, 182, 185, 187, 189, 196 Hydrolysis, 38, 162, 177, 193, 195 Hydrophobic, 177, 182 Hydroxylysine, 163, 177 Hydroxyproline, 154, 163, 177 Hyperandrogenism, 22, 26, 177 Hypercholesterolemia, 7, 67, 71, 94, 117, 167, 177 Hyperglycemia, 6, 10, 18, 19, 20, 31, 33, 41, 86, 97, 109, 110, 116, 117, 120, 177 Hyperlipidaemia, 54, 177 Hyperlipidemia, 67, 109, 167, 177 Hyperlipoproteinemia, 177, 178 Hypersensitivity, 153, 165, 177, 199 Hyperthyroidism, 65, 68, 178 Hypertriglyceridemia, 34, 43, 51, 68, 71, 103, 167, 178 Hypertrophy, 178, 194 Hypoglycemia, 18, 20, 109, 113, 117, 120, 121, 172, 178 Hypoglycemic, 39, 101, 108, 173, 178 Hypoglycemic Agents, 108, 178 Hypogonadism, 49, 178 Hypothalamic, 30, 35, 40, 101, 178 Hypothalamus, 178, 192, 201 Hypoxemia, 15, 178 Hypoxia, 31, 178 I Iatrogenic, 19, 178 Idiopathic, 71, 178 Ileal, 117, 178 Ileum, 178, 207 Immune response, 152, 156, 157, 165, 178, 179, 202, 207 Immune system, 158, 178, 179, 183, 185, 191, 208

Immunization, 178, 179, 194 Immunogenic, 178, 182 Immunoglobulin, 155, 178, 185 Immunologic, 161, 173, 178 Immunology, 152, 178 Immunophilins, 179, 200 Immunosuppressant, 179, 200 Immunosuppression, 25, 69, 179, 183 Immunosuppressive, 25, 174, 179, 203 Immunosuppressive Agents, 179 Immunotherapy, 158, 165, 179 Impairment, 15, 22, 30, 116, 118, 119, 121, 161, 170, 179, 184 Implantation, 163, 179, 188 Impotence, 179, 208 In vitro, 22, 31, 43, 168, 173, 179, 203 In vivo, 16, 24, 31, 36, 173, 176, 179, 183, 203 Incision, 159, 179 Incubation, 12, 179 Induction, 25, 94, 99, 155, 172, 179, 207 Infancy, 101, 179 Infantile, 179, 182 Infarction, 179 Infection, 17, 18, 42, 114, 156, 158, 161, 162, 166, 170, 179, 183, 187, 190, 199, 202, 208 Infertility, 22, 180 Inflammation, 38, 42, 151, 153, 156, 162, 170, 171, 173, 176, 180, 189, 191, 192, 198, 206 Infusion, 24, 31, 75, 180 Ingestion, 98, 172, 174, 180, 203 Initiation, 86, 180, 205 Inoperable, 109, 180 Inorganic, 162, 180 Inositol, 22, 180 Insight, 42, 180 Insulator, 180, 185 Insulin-dependent diabetes mellitus, 59, 60, 61, 73, 76, 80, 180 Insulin-like, 54, 87, 180 Intermittent, 15, 117, 171, 180, 193 Interstitial, 180, 198 Intestinal, 44, 160, 174, 180, 183 Intestinal Mucosa, 160, 180 Intestine, 158, 180, 184, 201 Intoxication, 180, 206 Intracellular, 22, 159, 179, 180, 183, 187, 193, 197, 199 Intramuscular, 23, 180, 190 Intravenous, 5, 14, 29, 180, 190 Involuntary, 180, 186, 197

215

Ions, 159, 167, 168, 177, 180 Iris, 155, 180 Islet, 5, 20, 27, 35, 66, 78, 109, 181 J Jejunostomy, 169, 181 K Kb, 132, 181 Ketoacidosis, 57, 181 Ketone Bodies, 181 Ketosis, 181 Kidney stone, 181, 206 Kinetics, 159, 181 L Labile, 163, 181 Lactation, 181, 188 Latent, 9, 181, 194 Least-Squares Analysis, 181, 197 Lens, 160, 181 Leptin, 15, 24, 29, 35, 181 Lesion, 171, 181, 182 Leukemia, 173, 181 Leukocytes, 159, 161, 181 Libido, 155, 181 Ligaments, 164, 181 Ligation, 12, 182 Likelihood Functions, 182, 197 Linear Models, 9, 182, 197 Linkage, 16, 182 Lipid, 7, 9, 16, 23, 29, 33, 36, 60, 75, 156, 180, 182, 185, 189, 205 Lipid A, 16, 75, 182 Lipid Peroxidation, 182, 189 Lipodystrophy, 25, 100, 182 Lipopolysaccharides, 182 Lipoprotein, 9, 10, 73, 109, 167, 182, 183 Liver Cirrhosis, 53, 182 Localization, 8, 182 Localized, 154, 177, 179, 182, 192 Logistic Models, 182, 197 Longitudinal study, 23, 182 Low-density lipoprotein, 167, 182, 183 Lymph, 162, 168, 183 Lymphatic, 168, 179, 183, 201 Lymphoblasts, 151, 183 Lymphocyte, 156, 179, 183 Lymphocyte Depletion, 179, 183 Lymphoid, 155, 183 Lysosomal Storage Diseases, 183, 185 M Macrophage, 43, 183 Malabsorption, 62, 160, 183 Malignancy, 29, 66, 183

Malignant, 73, 156, 183, 186, 203 Malnutrition, 85, 115, 117, 153, 157, 183 Mandible, 154, 161, 183, 198 Manifest, 14, 20, 63, 183 Meat, 183, 199 Mediate, 17, 35, 46, 183 Mediator, 22, 27, 183, 200 Medical Records, 183, 198 Medicament, 111, 183 MEDLINE, 133, 184 Meiosis, 184, 203 Melanin, 181, 184, 191, 205 Membrane, 19, 22, 31, 38, 161, 163, 166, 170, 184, 189, 191, 198 Memory, 155, 184 Meninges, 161, 184 Menopause, 184, 188, 193, 194 Mental, iv, 8, 49, 132, 134, 161, 163, 167, 184, 194, 196, 199, 206 Mental Disorders, 184, 194 Mental Health, iv, 8, 132, 134, 184, 194, 196 Mental Retardation, 49, 184 Metabolic acidosis, 4, 64, 184 Metabolic Clearance Rate, 116, 184 Metabolic disorder, 166, 174, 184 Metabolite, 23, 184 MI, 56, 67, 109, 149, 184 Microbe, 184, 204 Microbiology, 151, 184 Microcirculation, 182, 184 Micronutrients, 108, 121, 184 Microorganism, 184, 190, 207 Midaxillary line, 184, 208 Millimeter, 185, 208 Mineralocorticoids, 152, 164, 185 Minority Groups, 26, 185 Mitochondrial Swelling, 185, 186 Modification, 26, 33, 154, 185, 196 Molecular, 8, 11, 12, 17, 27, 32, 36, 38, 43, 44, 45, 133, 135, 158, 163, 172, 176, 185, 197, 204 Molecule, 19, 23, 156, 163, 167, 169, 177, 185, 189, 197, 205, 206 Monitor, 34, 165, 185, 187 Monoclonal, 36, 185 Monoclonal antibodies, 36, 185 Monocyte, 42, 185 Mononuclear, 41, 46, 185 Morphology, 25, 160, 185 Motility, 172, 185, 200 Motor nerve, 185, 188

216

Glucose Intolerance

Mucopolysaccharidoses, 117, 185 Multicenter study, 26, 185 Multiple sclerosis, 38, 185 Muscle Fibers, 27, 186 Mutagenesis, 35, 186 Mutagens, 186 Mydriatic, 186, 208 Myelin, 185, 186 Myocardial infarction, 62, 164, 184, 186 Myocardial Ischemia, 164, 186 Myocardium, 184, 186 Myotonic Dystrophy, 79, 186 N Nasogastric, 169, 186 Nausea, 181, 186, 206 Necrosis, 25, 179, 184, 186 Neonatal, 18, 19, 76, 83, 123, 186 Neoplasm, 73, 186 Nephrogenic, 73, 186 Nephropathy, 25, 186 Nerve, 49, 152, 161, 171, 172, 183, 185, 186, 188, 198, 199, 202, 205, 206 Nervous System, 152, 161, 183, 186, 187, 191, 203 Neural, 44, 152, 154, 172, 186 Neural Pathways, 44, 186 Neuromuscular, 151, 187, 206 Neuronal, 35, 159, 187 Neurons, 172, 187, 203 Neuropathy, 79, 99, 113, 187 Neuropeptide, 35, 187 Neurosecretory Systems, 168, 187 Neurotransmitter, 151, 154, 159, 174, 187, 201, 202 Neutrons, 153, 187, 197 Nitric Oxide, 103, 187 Nitrogen, 76, 110, 119, 121, 153, 155, 187, 205 Norepinephrine, 152, 187 Nuclear, 168, 172, 186, 187 Nuclei, 153, 168, 173, 187, 188, 196 Nucleic acid, 186, 187, 196 Nucleus, 165, 166, 184, 185, 187, 188, 195, 196, 202 Nutritional Status, 121, 188 Nutritional Support, 119, 121, 172, 188 Nutritive Value, 171, 188 O Observational study, 54, 188 Obstetrics, 30, 49, 52, 60, 64, 74, 91, 123, 188 Oculomotor, 89, 188

Oculomotor Nerve, 89, 188 Odds Ratio, 5, 188 Odour, 188, 206 Oestrogen, 72, 188 Oligomenorrhea, 188, 192 Omega-3 fatty acid, 100, 188 Oncology, 12, 45, 189 Opacity, 160, 165, 189 Optic cup, 155, 189 Osmotic, 153, 185, 189 Osteoclasts, 38, 189 Osteoporosis, 25, 38, 188, 189 Ovariectomy, 102, 189 Ovaries, 177, 189, 192, 200 Ovary, 16, 21, 155, 175, 188, 189 Overweight, 6, 59, 68, 95, 189 Ovulation, 155, 189 Ovum, 173, 189, 194 Oxidation, 16, 151, 156, 174, 182, 189 Oxidative Stress, 70, 189 Oxygenation, 178, 189 P Palliative, 188, 189, 204 Palsy, 89, 189 Pancreas, 35, 109, 151, 158, 166, 172, 176, 180, 181, 189, 195, 201, 205 Pancreatic, 5, 14, 16, 27, 32, 35, 37, 42, 50, 52, 65, 71, 78, 100, 160, 189 Pancreatic cancer, 14, 78, 189 Pancreatitis, 87, 189 Parathyroid, 48, 190, 203 Parathyroid Glands, 190 Parathyroid hormone, 48, 190 Parenteral, 99, 117, 119, 121, 190 Parenteral Nutrition, 99, 117, 119, 121, 190 Parity, 6, 190 Partial remission, 190, 198 Particle, 9, 190, 205 Partnership Practice, 190, 194 Parturition, 188, 190 Pathogen, 179, 190 Pathogenesis, 4, 5, 17, 22, 27, 30, 41, 78, 84, 114, 190 Pathologic, 47, 151, 158, 164, 177, 190, 198, 206 Pathologies, 29, 190 Pathophysiology, 120, 190 Patient Education, 114, 138, 144, 146, 149, 190 Pediatrics, 8, 11, 12, 15, 27, 29, 32, 34, 45, 62, 83, 100, 190 Pelvis, 151, 181, 189, 190, 206

217

Penicillin, 155, 190 Peptide, 8, 43, 62, 111, 154, 168, 181, 190, 193, 195 Perfusion, 31, 81, 178, 190 Perinatal, 11, 31, 34, 57, 74, 79, 191 Perindopril, 60, 191 Periodontal disease, 89, 191 Periodontitis, 173, 191 Peripheral Nervous System, 187, 189, 191, 201, 202 Phagocyte, 41, 191 Pharmaceutic Aids, 171, 191 Pharmacologic, 9, 114, 191, 204, 206 Phenotype, 10, 16, 21, 35, 36, 44, 82, 191 Phenylalanine, 191, 205 Phlebotomy, 14, 191 Phosphodiesterase, 36, 191 Phospholipids, 170, 180, 182, 191 Phosphorus, 159, 190, 191, 192 Phosphorylated, 21, 42, 192 Phosphorylation, 12, 20, 21, 23, 27, 38, 42, 192 Photosensitivity, 192, 193 Physical Examination, 14, 120, 173, 192 Physiologic, 12, 32, 40, 42, 153, 158, 184, 192, 197, 198 Physiology, 12, 18, 20, 27, 41, 45, 64, 69, 75, 86, 94, 97, 99, 101, 168, 172, 192 Pilot study, 38, 192 Pituitary Gland, 164, 192 Plants, 153, 159, 174, 185, 187, 192, 193, 199, 204 Plasma cells, 155, 192 Plasma protein, 153, 168, 192 Platelet Aggregation, 154, 187, 192 Platelets, 70, 187, 192, 204 Platinum, 162, 192 Pneumonia, 164, 192 Polycystic, 16, 51, 53, 116, 177, 192 Polycystic Ovary Syndrome, 51, 53, 177, 192 Polygenic Inheritance, 10, 193 Polymerase, 193, 198 Polymorphic, 38, 193 Polymorphism, 51, 82, 83, 193 Polypeptide, 42, 78, 154, 162, 172, 193, 201 Polysaccharide, 108, 156, 193 Polyunsaturated fat, 51, 108, 193 Porphyria, 117, 191, 193 Porphyria Cutanea Tarda, 117, 191, 193 Porphyria, Hepatic, 193 Porphyrins, 193

Posterior, 154, 181, 184, 189, 193 Postmenopausal, 69, 189, 193 Postnatal, 35, 74, 193, 202 Postoperative, 69, 119, 193 Postprandial, 88, 108, 110, 116, 193 Potassium, 121, 167, 185, 193 Potentiate, 15, 193 Practice Guidelines, 134, 194 Prazosin, 94, 194 Precursor, 36, 155, 167, 169, 187, 191, 194, 205 Predisposition, 34, 98, 194 Prednisolone, 194 Prednisone, 25, 194 Pre-Eclampsia, 67, 194 Pregnancy Outcome, 18, 19, 31, 194 Pregnancy Tests, 173, 194 Premenopausal, 16, 194 Prevalence, 4, 7, 9, 11, 14, 30, 38, 40, 43, 57, 59, 61, 78, 80, 81, 88, 94, 114, 117, 118, 188, 194 Primary Prevention, 39, 114, 194 Private Practice, 30, 194 Probe, 42, 194 Progeny, 35, 95, 194 Progesterone, 194, 202 Progression, 32, 41, 66, 155, 195 Progressive, 11, 20, 29, 35, 75, 160, 162, 167, 185, 186, 195, 198 Proinsulin, 50, 67, 78, 109, 195, 196 Proline, 162, 177, 195 Prone, 32, 195 Prophase, 195, 203 Prophylaxis, 29, 195 Prospective Studies, 37, 195 Prospective study, 182, 195 Prostate, 158, 188, 195, 205 Protease, 17, 18, 34, 57, 195 Protease Inhibitors, 17, 34, 195 Protein C, 153, 154, 156, 157, 171, 182, 195, 206 Protein S, 158, 195, 199 Proteinuria, 174, 194, 195 Proteolytic, 153, 163, 195 Protocol, 25, 31, 33, 39, 195 Protons, 153, 177, 196, 197 Pruritus, 196, 206 Psychic, 181, 184, 196 Puberty, 9, 196 Public Health, 11, 15, 16, 33, 41, 49, 94, 114, 134, 196 Public Policy, 133, 196

218

Glucose Intolerance

Publishing, 47, 196 Puerperium, 188, 196 Pulmonary, 72, 89, 119, 158, 170, 176, 196, 207 Pulmonary Artery, 158, 196, 207 Pulse, 51, 185, 196 Purified Insulins, 195, 196 Purifying, 21, 196 Purines, 196, 200 Pyrimidines, 196, 200 Q Quality of Life, 6, 28, 33, 196 R Race, 15, 196 Radiation, 29, 172, 179, 196, 197, 208 Radioactive, 177, 179, 185, 187, 197 Radiography, 173, 197 Random Allocation, 197 Randomization, 33, 39, 197 Randomized, 7, 33, 37, 39, 167, 197 Randomized clinical trial, 33, 197 Reabsorption, 118, 121, 197 Receptor, 12, 16, 20, 23, 24, 27, 41, 46, 52, 73, 84, 90, 102, 151, 156, 197, 200 Receptors, Serotonin, 197, 200 Recurrence, 162, 197 Red blood cells, 169, 193, 197, 199 Refer, 1, 163, 182, 187, 197, 204 Reflex, 44, 197 Refraction, 197, 201 Regimen, 25, 167, 197 Regression Analysis, 5, 197 Rehydration, 82, 198 Remission, 62, 197, 198 Renal failure, 41, 46, 116, 118, 119, 121, 198 Reproduction Techniques, 194, 198 Research Support, 12, 23, 45, 198 Resection, 63, 198 Resorption, 38, 189, 197, 198 Respiration, 156, 185, 198 Resting metabolic rate, 33, 198 Retina, 166, 181, 198, 199 Retinal, 166, 198 Retinopathy, 49, 166, 198 Retrospective, 62, 198 Retrospective study, 62, 198 Reverse Transcriptase Inhibitors, 19, 198 Rheumatism, 198, 199 Rheumatoid, 38, 199 Rheumatoid arthritis, 38, 199 Ribosome, 199, 205 Risk patient, 39, 199

Rod, 162, 199 S Saliva, 184, 199 Salivary, 166, 189, 199 Saponins, 199, 202 Saturated fat, 108, 199 Sclerosis, 156, 185, 199 Screening, 6, 14, 31, 33, 39, 55, 57, 64, 84, 91, 114, 162, 199 Sebaceous, 199, 207 Sebaceous gland, 199, 207 Secretory, 20, 71, 199 Sedentary, 4, 27, 115, 198, 199 Segmental, 174, 199 Selenium, 13, 46, 118, 199 Senescence, 44, 199 Senile, 85, 189, 200 Sepsis, 31, 85, 184, 200 Septic, 31, 86, 200 Sequencing, 21, 200 Serine, 27, 168, 200 Serotonin, 103, 171, 187, 197, 200, 205 Serous, 168, 200 Serum, 4, 15, 22, 37, 39, 52, 60, 62, 67, 76, 85, 87, 98, 103, 153, 154, 163, 183, 185, 200 Sex Characteristics, 152, 155, 188, 196, 200, 203 Shock, 200, 205 Side effect, 25, 152, 158, 200, 204 Signs and Symptoms, 120, 198, 200, 206 Silicon, 118, 200 Silicon Dioxide, 200 Sirolimus, 25, 179, 200 Skeletal, 16, 17, 19, 21, 22, 23, 27, 28, 31, 32, 35, 36, 37, 97, 116, 155, 162, 200, 204 Skeleton, 200 Sleep apnea, 15, 200 Small intestine, 162, 165, 167, 177, 178, 180, 186, 201 Social Environment, 196, 201 Sodium, 121, 167, 185, 197, 201, 202 Soft tissue, 42, 159, 200, 201 Solvent, 170, 189, 201 Somatic, 152, 184, 191, 201, 203, 206 Somatostatin, 86, 103, 201 Soybean Oil, 193, 201 Specialist, 140, 201 Species, 153, 169, 177, 184, 185, 196, 201, 205, 207, 208 Specificity, 153, 159, 168, 201 Spectrum, 3, 11, 29, 185, 201

219

Sperm, 155, 161, 201 Spinal cord, 64, 161, 172, 184, 186, 187, 191, 197, 201, 203 Spirochete, 201, 203 Spleen, 154, 183, 201 Spontaneous Abortion, 194, 201 Sporadic, 14, 193, 201 Sprue, 138, 139, 202 Steatosis, 117, 171, 202 Steel, 162, 202, 206 Stem Cells, 35, 202 Sterile, 190, 202 Sterility, 180, 202 Steroid, 8, 25, 116, 155, 157, 165, 188, 199, 202 Stillbirth, 194, 202 Stimulus, 42, 157, 167, 197, 202, 204 Stomach, 151, 157, 166, 169, 172, 174, 177, 181, 186, 201, 202 Strand, 44, 193, 202 Stress, 40, 56, 98, 102, 165, 186, 189, 194, 199, 202 Stroke, 57, 132, 160, 202 Subacute, 179, 202 Subclinical, 87, 94, 126, 179, 202 Subcutaneous, 74, 152, 167, 182, 190, 202, 208 Substance P, 184, 199, 202 Substrate, 20, 23, 35, 202 Suction, 171, 202 Supplementation, 29, 99, 101, 103, 202 Suppression, 16, 34, 164, 202 Sweat, 184, 202 Sympathetic Nervous System, 155, 203 Sympathomimetic, 53, 169, 187, 203 Symptomatic, 189, 203 Synapse, 152, 203, 205 Synaptic, 8, 187, 203 Syphilis, 85, 203 Systemic, 35, 47, 154, 158, 169, 179, 194, 203 Systolic, 178, 203 T Tacrolimus, 25, 179, 203 Telomerase, 44, 203 Telomere, 44, 203 Terbutaline, 74, 203 Testis, 155, 188, 203 Testosterone, 16, 26, 40, 155, 203 Tetany, 190, 203 Therapeutics, 60, 101, 203 Thinness, 119, 204

Thorax, 151, 204, 206 Threonine, 200, 204 Threshold, 14, 178, 204 Thrombocytes, 192, 204 Thrombosis, 82, 195, 202, 204 Thyroid, 76, 89, 117, 178, 190, 204, 205 Thyroid Gland, 178, 190, 204 Thyrotoxicosis, 117, 204 Thyroxine, 153, 191, 204 Tocolysis, 30, 204 Tolerance, 4, 5, 6, 7, 14, 15, 17, 18, 19, 22, 24, 26, 27, 28, 32, 33, 37, 39, 41, 43, 95, 97, 98, 100, 101, 109, 115, 116, 118, 174, 204 Tooth Preparation, 151, 204 Topical, 170, 204 Toxic, iv, 118, 165, 167, 173, 187, 199, 204 Toxicity, 13, 46, 103, 167, 204 Toxicology, 134, 204 Toxin, 169, 204 Trace element, 118, 161, 200, 204 Trachea, 159, 204 Traction, 162, 205 Transcriptase, 198, 203, 205 Transcription Factors, 36, 205 Transduction, 23, 38, 180, 205 Transfection, 158, 173, 205 Translation, 12, 45, 154, 205 Translocation, 22, 24, 27, 205 Transmitter, 151, 183, 187, 205 Transplantation, 25, 35, 51, 52, 59, 69, 88, 162, 168, 178, 183, 205 Trauma, 50, 86, 119, 186, 190, 205 Triglyceride, 9, 75, 109, 119, 177, 178, 205 Troglitazone, 26, 116, 205 Trophic, 40, 205 Truncal, 10, 205 Tryptophan, 163, 200, 205 Tumor marker, 158, 205 Tyrosine, 24, 38, 95, 160, 205 U Ultrafiltration, 176, 205 Ultrasonography, 173, 206 Uraemia, 59, 190, 206 Urea, 157, 158, 203, 206 Uremia, 65, 78, 84, 88, 116, 118, 198, 206 Uric, 67, 196, 206 Urinary, 121, 194, 206 Urinary Retention, 194, 206 Urine, 156, 158, 165, 166, 167, 175, 181, 186, 195, 206

220

Glucose Intolerance

Uroporphyrinogen Decarboxylase, 193, 206 Uterine Contraction, 151, 204, 206 Uterus, 151, 172, 189, 194, 206 V Vagus Nerve, 205, 206 Vanadium, 118, 206 Vascular, 29, 30, 40, 41, 46, 51, 72, 82, 159, 166, 168, 169, 179, 182, 184, 187, 204, 206 Vasculitis, 190, 206 Vasoconstriction, 169, 206 Vasodilator, 156, 159, 206 Vector, 205, 206 Vein, 44, 157, 180, 187, 191, 206 Venereal, 203, 207 Venous, 33, 157, 165, 195, 207 Ventral, 178, 188, 207 Ventricle, 178, 196, 203, 207 Ventricular, 48, 207 Venules, 158, 159, 168, 184, 207 Vertebrae, 201, 207 Vesicular, 23, 207 Veterinary Medicine, 133, 207 Villous, 160, 207

Viral, 34, 79, 205, 207 Viral Hepatitis, 79, 207 Virilism, 177, 207 Virilization, 8, 207 Virulence, 157, 204, 207 Virus, 157, 205, 207 Visceral, 34, 206, 207 Vitamin A, 180, 207 Vitreous, 166, 181, 198, 207 Vitreous Hemorrhage, 166, 207 Vitro, 31, 176, 207 Vivo, 36, 183, 207 W Waist circumference, 53, 207 White blood cell, 151, 155, 181, 183, 185, 192, 208 Windpipe, 204, 208 Wound Healing, 42, 46, 208 X Xenograft, 155, 208 X-ray, 37, 187, 208 Y Yeasts, 191, 208 Yohimbine, 94, 208