HYPOGLYCEMIA A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R EFERENCES
J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS
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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright ©2003 by ICON Group International, Inc. Copyright ©2003 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1
Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Hypoglycemia: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-597-83940-9 1. Hypoglycemia-Popular works. I. Title.
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Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors, or authors. ICON Group International, Inc., the editors, and the authors are not responsible for the content of any Web pages or publications referenced in this publication.
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Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on hypoglycemia. 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 HYPOGLYCEMIA ....................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Hypoglycemia ............................................................................. 14 E-Journals: PubMed Central ....................................................................................................... 71 The National Library of Medicine: PubMed ................................................................................ 72 CHAPTER 2. NUTRITION AND HYPOGLYCEMIA............................................................................ 113 Overview.................................................................................................................................... 113 Finding Nutrition Studies on Hypoglycemia ............................................................................ 113 Federal Resources on Nutrition ................................................................................................. 117 Additional Web Resources ......................................................................................................... 117 CHAPTER 3. ALTERNATIVE MEDICINE AND HYPOGLYCEMIA ..................................................... 121 Overview.................................................................................................................................... 121 National Center for Complementary and Alternative Medicine................................................ 121 Additional Web Resources ......................................................................................................... 128 General References ..................................................................................................................... 133 CHAPTER 4. DISSERTATIONS ON HYPOGLYCEMIA ....................................................................... 135 Overview.................................................................................................................................... 135 Dissertations on Hypoglycemia ................................................................................................. 135 Keeping Current ........................................................................................................................ 136 CHAPTER 5. CLINICAL TRIALS AND HYPOGLYCEMIA .................................................................. 137 Overview.................................................................................................................................... 137 Recent Trials on Hypoglycemia ................................................................................................. 137 Keeping Current on Clinical Trials ........................................................................................... 138 CHAPTER 6. PATENTS ON HYPOGLYCEMIA .................................................................................. 141 Overview.................................................................................................................................... 141 Patents on Hypoglycemia .......................................................................................................... 141 Patent Applications on Hypoglycemia....................................................................................... 161 Keeping Current ........................................................................................................................ 184 CHAPTER 7. BOOKS ON HYPOGLYCEMIA ...................................................................................... 185 Overview.................................................................................................................................... 185 Book Summaries: Federal Agencies............................................................................................ 185 Book Summaries: Online Booksellers......................................................................................... 220 The National Library of Medicine Book Index ........................................................................... 223 Chapters on Hypoglycemia ........................................................................................................ 225 CHAPTER 8. MULTIMEDIA ON HYPOGLYCEMIA ........................................................................... 235 Overview.................................................................................................................................... 235 Video Recordings ....................................................................................................................... 235 Audio Recordings....................................................................................................................... 236 Bibliography: Multimedia on Hypoglycemia ............................................................................. 237 CHAPTER 9. PERIODICALS AND NEWS ON HYPOGLYCEMIA ........................................................ 239 Overview.................................................................................................................................... 239 News Services and Press Releases.............................................................................................. 239 Newsletter Articles .................................................................................................................... 242 Academic Periodicals covering Hypoglycemia........................................................................... 243 CHAPTER 10. RESEARCHING MEDICATIONS................................................................................. 245 Overview.................................................................................................................................... 245 U.S. Pharmacopeia..................................................................................................................... 245 Commercial Databases ............................................................................................................... 246 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 251
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Overview.................................................................................................................................... 251 NIH Guidelines.......................................................................................................................... 251 NIH Databases........................................................................................................................... 253 Other Commercial Databases..................................................................................................... 256 The Genome Project and Hypoglycemia .................................................................................... 257 APPENDIX B. PATIENT RESOURCES ............................................................................................... 261 Overview.................................................................................................................................... 261 Patient Guideline Sources.......................................................................................................... 261 Finding Associations.................................................................................................................. 269 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 271 Overview.................................................................................................................................... 271 Preparation................................................................................................................................. 271 Finding a Local Medical Library................................................................................................ 271 Medical Libraries in the U.S. and Canada ................................................................................. 271 ONLINE GLOSSARIES................................................................................................................ 277 Online Dictionary Directories ................................................................................................... 280 HYPOGLYCEMIA DICTIONARY ............................................................................................. 281 INDEX .............................................................................................................................................. 375
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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 hypoglycemia 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 hypoglycemia, 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 hypoglycemia, 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 hypoglycemia. 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 hypoglycemia, 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 hypoglycemia. 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 HYPOGLYCEMIA Overview In this chapter, we will show you how to locate peer-reviewed references and studies on hypoglycemia.
The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and hypoglycemia, 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 “hypoglycemia” (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: •
Hypoglycemia and Driving Source: Practical Diabetology. 21(4): 20-23. June 2002. Contact: Available from R.A. Rapaport Publishing, Inc. 150 West 22nd Street, New York, NY 10011. (800) 234-0923. Summary: Although it comes as no surprise to health care providers that hypoglycemia (low blood glucose levels) and driving are a dangerous combination that threatens the safety of many persons with diabetes and their passengers, it may be surprising to learn that little information is available regarding the magnitude of this problem. This article reviews the literature on the issues of hypoglycemia (low blood glucose levels) and driving. The authors discuss the effects of hypoglycemia on driving ability, the decision to drive, how to interpret the information on hypoglycemia and driving, and the role of
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the practitioner in reducing the risk of hypoglycemia and driving. The current data demonstrate the hypoglycemia, even as mild as 65 milligrams per deciliter, can impair driving abilities; that previous driving experience and perceived driving skills cannot be relied upon to ensure a safe drive; and that perceived ability to detect low blood glucose may not always predict accurate detection of low blood glucose. 2 figures. 14 references. •
Hypoglycemia: An Excuse for Poor Glycemic Control? Source: Clinical Diabetes. 19(4): 161-167. 2001. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: Although long term maintenance of normoglycemia (normal levels of blood glucose, or sugar) can prevent the onset and delay the progression of the microvascular (small blood vessels) complications of diabetes, a large percentage of patients with diabetes continue to have poorly controlled glucose levels. The risk of hypoglycemia (low levels of blood glucose) is a real obstacle to achieving glucose targets in patients with type 1 diabetes. However, risk of severe hypoglycemia in type 2 diabetes is minimal and should not be used as an excuse for failing to achieve glycemic goals. This article reviews the incidence of severe hypoglycemia in the major diabetes trials, the results of attempts to optimize glycemia to date, and the ways to ameliorate severe hypoglycemia in the treatment of both type 1 and type 2 diabetes. Strategies recommended for type 1 diabetes include: monitor blood glucose levels frequently; use physiological models of insulin replacement (such as multiple daily insulin injections and the newer types of insulin); avoid between meal snacks; consider the potential role of continuous glucose monitoring; and educate oneself, particularly about hypoglycemia. Severe hypoglycemia is relatively rare in patients with type 2 diabetes, however risk factors may include: a history of severe hypoglycemia, negative C peptide levels, a low level of diabetes education, or hypoglycemia unawareness. The authors conclude that patient education, empowerment, self monitoring of blood glucose (SMBG), more flexible and physiological insulin replacement regimens, and professional support can all minimize the frequency of severe hypoglycemia. 2 figures. 39 references.
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Hypoglycemia and Employment/Licensure Source: Diabetes Care. 25(Supplement 1): S132. January 2002. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: Despite the significant medical and technological advances made in managing diabetes, discrimination in employment and licensure against people with diabetes still occurs. This discrimination is often based on apprehension that the person with diabetes may present a safety risk to the employer or the public. Perhaps the greatest concern is that hypoglycemia (low blood glucose levels) will cause sudden unexpected incapacitation. This brief article presents the American Diabetes Association position statement on hypoglycemia and employment or licensure. The article notes that hypoglycemia usually occurs gradually and is generally associated with typical warning signs, which may include rapid heartbeat, perspiration, shakiness, anxiety, and hunger. A hypoglycemic reaction is not ordinarily associated with a loss of consciousness or a seizure. Those who experience recurrent episodes of severe hypoglycemia should be individually evaluated and, when appropriate, the employment position should be modified. In addition, the proper use of systems that allow rapid and accurate selfmonitoring of blood glucose levels can assist people in avoiding significant
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hypoglycemia. The article concludes that, because the effects of diabetes are unique to each individual, it is inappropriate to consider all people with diabetes the same. 1 reference. •
Hypoglycemia in Elderly Patients Treated with Oral Agents Source: Practical Diabetology. 21(4): 7-14. June 2002. Contact: Available from R.A. Rapaport Publishing, Inc. 150 West 22nd Street, New York, NY 10011. (800) 234-0923. Summary: Elderly patients with type 2 diabetes who take antidiabetes medication are at increased risk for hypoglycemia (low levels of blood glucose). Whether there may be clinically significant advantages in the choice of available oral therapies, particularly the insulin secretagogues, for this population is unclear. This review article addresses this issue. The authors note that, as in younger patients with diabetes, the elderly need good glycemic control to prevent or delay diabetic complications. However, elderly patients are more susceptible to the development of hypoglycemia, which presents a particularly serious threat in this population. Fortunately, several newer insulin secretagogues are now available that, when used alone or in combination, can control hyperglycemia in older patients with much less risk of dangerously low levels of blood glucose. The authors discuss the choice of appropriate medications, other preventive strategies, how to treat hypoglycemic episodes, the classification of hypoglycemia by severity, and the reasons why the elderly are at higher risk for hypoglycemia. 2 figures. 1 table. 21 references.
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Acute Hypoglycemia in Humans Causes Attentional Dysfunction While Nonverbal Intelligence is Preserved Source: Diabetes Care. 24(10): 1745-1750. October 2001. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: Experimentally induced hypoglycemia (low blood glucose, or sugar) in humans causes progressive but reversible cognitive dysfunction, but it is not known to what extent neuropsychological tests measure the abilities of cognitive functioning that are important in everyday life. This article reports on a study that examined the effects of acute insulin induced hypoglycemia on attention and intelligence in adults who do not have diabetes. Results showed that hypoglycemia induced a significant deterioration in tests sensitive to both visual and auditory selective attention. During hypoglycemia, attentional flexibility deteriorated and speed of information processing was delayed. Sustained attention was preserved and intelligence scores did not deteriorate during hypoglycemia. The authors conclude that, on the basis of these results, it can be surmised that many complex attention tasks relevant to everyday life are impaired during moderate hypoglycemia. In the context of hypoglycemia developing during everyday activities, examples of practical problems may include difficulty in filling out forms, interpreting timetables, or locating items on supermarket shelves. 1 table. 32 references.
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Negotiating the Barrier of Hypoglycemia in Diabetes Source: Diabetes Spectrum. 15(1): 20-27. 2002. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org.
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Summary: Hypoglycemia (low blood glucose level) is the limiting factor in the glycemic management of diabetes. This article offers strategies for negotiating the barrier of hypoglycemia in diabetes care. Hypoglycemia is a barrier to quality of life and even survival in the short term and to true glycemic control, with its concomitant benefits, in the long term. Although it is possible to both improve glycemic control and minimize the risk of hypoglycemia in many patients with currently available regimens, by applying the principles of aggressive therapy and practicing hypoglycemia risk reduction, people with diabetes need better treatment methods that provide glucoseregulated insulin secretion or replacement if optimal levels of glycemia are to be maintained safely over a lifetime of diabetes. The authors conclude that by practicing hypoglycemia risk reduction (addressing the issue, applying the principles of aggressive therapy, and considering both the conventional risk factors and those indicative of compromised glucose counterregulation) health care providers should strive to reduce mean glycemia as much as can be accomplished safely. 2 figures. 2 tables. 55 references. •
Administration of Neutral Protamine Hagedorn Insulin at Bedtime Versus with Dinner in Type 1 Diabetes Mellitus To Avoid Nocturnal Hypoglycemia and Improve Control Source: Annals of Internal Medicine. 136(7): 547-549. April 2, 2002. Contact: Available from American College of Physicians. American Society of Internal Medicine. 190 North Independence Mall West, Philadelphia, PA 19106-1572. Website: www.acponline.org. Summary: Intensive insulin treatment of type 1 diabetes mellitus increases the risk for nocturnal hypoglycemia (low levels of blood glucose overnight). This article reports on a study undertaken to demonstrate that splitting the evening insulin regimen reduces the risk for nocturnal hypoglycemia in the intensive treatment of people with type 1 diabetes mellitus (n = 22). Each patient was randomly assigned to one of the two insulin regimens for 4 months and then switched to the other regimen for another 4 months. The treatment regimens were: mixed treatment, i.e., a mixture of human regular and neutral protamine Hagedorn (NPH) insulin administered before dinner; and split treatment, i.e., human regular insulin administered at dinner and NPH insulin administered at bedtime. During the split regimen treatment period, patients had fewer episodes of nocturnal hypoglycemia, a lower fasting blood glucose level, less variable fasting blood glucose levels, and lower hemoglobin A1c values (a measure of blood glucose over time) than during the mixed regimen. 5 figures. 2 tables. 45 references.
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Spurious Reporting of Nocturnal Hypoglycemia by CGMS in Patients With Tightly Controlled Type 1 Diabetes Source: Diabetes Care. 25(9): 1499-1503. September 2002. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: The Medtronic MiniMed Continuous Glucose Monitoring System (CGMS) is designed to continuously monitor interstitial fluid glucose levels within a range of 40400 milligrams per deciliter. It is considered an important tool for overnight glucose monitoring. This article reports on a study undertaken to determine the accuracy of this system in individuals with tightly controlled diabetes. The study included 7 adolescents and young adults. Simultaneous glucose measurements obtained by glucose analyzer, Accu-Check Advantage meter, and CGMS were compared. The CGMS results were lower than analyzer readings in 74 percent of simultaneous pairs of tests performed
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during the 24 hour period of the study. There was a trend for the poorest correlation to occur in patients with the narrowest range in daily glucose levels. When the lowest CGMS reading of the night was compared with the simultaneous analyzer reading, the CGMS level was lower in all cases by an average of 38 percent (plus or minus 15 percent). In six of seven patients, the discrepancy was believed to be clinically significant; in at least four patients, overnight glucose levels reported by CGMS were falsely low, in a range that might have resulted in inappropriate reduction of overnight insulin dose. The authors conclude that CGMS reports of asymptomatic nighttime hypoglycemia (low blood glucose) may be spurious and should be interpreted with caution in patients with tightly controlled diabetes. 2 figures. 2 tables. 12 references. •
Do Sensor Glucose Levels Accurately Predict Plasma Glucose Concentrations During Hypoglycemia and Hyperinsulinemia? Source: Diabetes Care. 25(5): 889-893. May 2002. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: The MiniMed Continuous Glucose Monitoring System (CGMS) measures subcutaneous interstitial glucose levels that are calibrated against three of more fingerstick glucose levels daily. This article reports on a study undertaken to examine whether the relationship between plasma and interstitial fluid glucose is altered by changes in plasma glucose and insulin levels and how such alterations might influence CGMS performance. To achieve this, the authors used microdialysis to provide a means to measure changes in interstitial glucose levels directly. Results showed that although hyperinsulinemia (high levels of insulin in the blood) may contribute to modest discrepancies between plasma and sensor glucose levels, the CGMS is able to accurately track acute changes in plasma glucose when calibrated across a range of plasma glucose and insulin levels. 1 figure. 1 table. 13 references.
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Influence of Caffeine on the Frequency and Perception of Hypoglycemia in FreeLiving Patients with Type 1 Diabetes Source: Diabetes Care. 23(4): 455-459. April 2000. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: This article describes a prospective randomized placebo controlled double blind study that examined the influence of caffeine on the frequency and perception of hypoglycemia in free living patients who had type 1 diabetes. A total of 34 patients who had type 1 diabetes were recruited for the study. After a lead in phase and while adhering to a low caffeine diet, subjects were randomized to capsules containing either 200 milligrams of caffeine or matched placebo with crossover at 3 months. Hypoglycemic episodes were monitored throughout with capillary blood glucose readings and a symptom questionnaire. During the study, measurements of blood pressure, middle cerebral artery blood velocity, cognitive function, glycosylated hemoglobin levels, and lipid profiles were taken at the beginning and end of each phase. Throughout the study, no changes in glycemic control or lipid profile were evident. The number of symptomatic episodes was greater with caffeine and was associated with more intense warning symptoms. For women, caffeine ingestion caused a modest pressor response. Four choice reaction time improved slightly with caffeine supplementation. The article concludes that ingestion of modest amounts of caffeine enhances the intensity of hypoglycemia warning symptoms in patients who have type 1
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diabetes without altering the prevailing standard of glycemic control or increasing the incidence of severe hypoglycemic episodes. 3 figures. 2 tables. 24 references. (AA-M). •
Detection of Hypoglycemia with the GlucoWatch Biographer Source: Diabetes Care. 24(5): 881-885. May 2001. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: This article describes a study that evaluated the hypoglycemia alert performance of the GlucoWatch biographer in a large and demographically diverse patient population. Hypoglycemia was defined as blood glucose equal to or less than 3.9 mmol/l. The analysis was based on 1,091 biographer uses from four clinical trials, which generated 14,487 paired readings. Results show that, as the low glucose alert level of the biographer was increased, the number of true positive alerts and false positive alerts increased. In a home environment study, increasing the alert level from 3.9 to 5.6 mmol/l increased the true positive fraction by approximately 50 percent and the false positive fraction less than 10 percent. When analyzed as a function of varying low glucose alert levels, results show receiver operator characteristic curves consistent with a highly useful diagnostic tool. Setting the alert level from 1.1 to 1.7 mmol/l above the level of concern was likely to optimize the trade off between true positives and false positives for each user. When the same blood glucose data are analyzed for typical monitoring practices, results show that fewer hypoglycemic events were detected than those detected with the biographer. The article concludes that the frequent and automatic nature of the biographer readings allows more effective detection of hypoglycemia than that achieved with current medical practice. In addition, it provides low glucose alert levels that can be adjusted to the patient's need to achieve a higher detection frequency at the expense of additional false positive readings. 2 figures. 1 table. 15 references. (AA-M).
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All About Hypoglycemia Source: Diabetes Self-Management. 17(1): 21-22, 24, 26-27. January-February 2000. Contact: Available from R.A. Rapaport Publishing, Inc. 150 West 22nd Street, New York, NY 10011. (800) 234-0923. Summary: This article presents an overview of hypoglycemia. When blood sugar gets too low, a condition called hypoglycemia, the body and brain are unable to function properly. Although hypoglycemia is defined as any blood sugar level under 70 milligrams per deciliter, people may treat themselves for hypoglycemia at different levels. Common causes of hypoglycemia include too much insulin or other medicine, too little food, too much physical activity, alcohol consumption, certain prescription medications, the menstrual cycle, and gastroparesis. Many symptoms accompany low blood sugar levels, but the most common symptoms are rapid heartbeat, sweating, shakiness, trembling, tingling or numbness in hands, feet, or face, difficulty thinking or concentrating, blurred vision, slurred speech, poor coordination, sleepiness, hunger, nausea, and headache. Hypoglycemia can also result in changes in emotions. Some people are unable to feel symptoms of low blood sugar until levels drop dangerously low, a condition known as hypoglycemia unawareness. Many people experience hypoglycemic episodes during sleep. This is a risky period to have hypoglycemia since a person is less likely to be aware of any warning symptoms. Failure to treat nighttime episodes of hypoglycemia can result in elevated blood glucose levels the following day. Hypoglycemia is a particular problem for older adults with diabetes. Treating
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hypoglycemia involves testing blood glucose levels, eating or drinking 10 to 15 grams of a fast-acting carbohydrate, and retesting blood glucose levels. A glucagon injection may be needed if a person is able to self treat for hypoglycemia. The article offers tips for preventing hypoglycemia. •
Assessing and Treating Hypoglycemic Events Source: Patient Care. 33(8): 22-24, 29, 33-34, 36-38, 40. April 30, 1999. Contact: Available from Medical Economics. 5 Paragon Drive, Montvale, NJ 07645. (800) 432-4570. Fax (201) 573-4956. Summary: This article presents guidelines on assessing and treating hypoglycemic events. Hypoglycemia is a complication of type 1 and type 2 diabetes. Risk is highest in the most tightly controlled patients, especially children and adolescents. Additional risk factors include a history of hypoglycemic episodes, younger age, male sex, and intensive treatment regimens. Although some patients are asymptomatic despite significantly depressed levels of blood glucose, physicians need to remember that unsuspected hypoglycemia can masquerade as a psychiatric, neurologic, or cardiovascular disorder. Symptoms include fatigue, difficulty in speaking, headache, dizziness, confusion, inability to concentrate, and coma. The actual value that defines hypoglycemia is arbitrary, so the clinical state of the patient must be correlated with the glucose level. Various types of hypoglycemia, including postprandial hypoglycemia, are characterized as spontaneous. Other spontaneous types are alimentary hypoglycemia; idiopathic hypoglycemia; and hypoglycemia caused by insulinomas, tumors, endocrine related conditions, hepatic disease, and other conditions. The most common causes of induced hypoglycemia are drugs, particularly sulfonylureas such as chlorpropamide, alcohol, and salicylates. Occasionally, factitious hypoglycemia may occur when a person selfadministers insulin or an oral hypoglycemic drug to induce hypoglycemia. Treatment options include self administration of glucose, infusion of glucose in comatose patients, and administration of glucagon. Preventing hypoglycemic reactions involves teaching the patient to recognize the symptoms and avoid a full-blown episode by ingesting carbohydrate, prescribing a medical identification bracelet, reviewing drug therapy, and advising parents of children and adolescents who have tightly controlled diabetes how to assess adverse nocturnal hypoglycemic events. 2 figures. 2 tables. 2 references.
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Sleep-Related Hypoglycemia-Associated Autonomic Failure in Type 1 Diabetes Source: Diabetes. 52(5): 1195-1203. May 2003. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: This article reports on a study of sleep-related hypoglycemia, focusing on the defenses against developing hypoglycemia and how sleep affects them. The authors studied eight adult patients with uncomplicated type 1 diabetes and eight matched nondiabetic control subjects with hyperinsulinemic stepped hypoglycemic clamps. Subjects were tested in the morning, while awake and at night, while awake throughout, and while asleep. Plasma epinephrine, plasma norepinephrine, and pancreatic polypeptide responses to hypoglycemia were reduced during sleep in subjects with diabetes, but not in the control subjects. The diabetes subjects exhibited markedly reduced awakening from sleep during hypoglycemia. Sleep efficiency (percent time asleep) was 77 percent (plus or minus 18 percent) in the subjects with diabetes, but only 26 percent (plus or minus 8 percent) in the control subjects late in the 45 milligram per deciliter hypoglycemic steps. The authors conclude that autonomic responses to
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hypoglycemia are reduced during sleep in type 1 diabetes. Also, probably because of their reduced sympathoadrenal responses, patients with type 1 diabetes are substantially less likely to be awakened by hypoglycemia. Thus, both physiological and behavioral defenses are further compromised during sleep. This sleep-related hypoglycemia-associated autonomic failure, in the context of imperfect insulin replacement, likely explains the high frequency of nocturnal hypoglycemia in type 1 diabetes. 10 figures. 6 tables. 27 references. •
Glucose Monitoring of the Arm: Risky Delays of Hypoglycemia and Hyperglycemia Detection Source: Diabetes Care. 25(6): 956-960. June 2002. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: This article reports on a study that examined whether rapid changes in blood glucose (BG) result in clinically relevant differences between capillary BG values measured at the forearm and the fingertip and whether local rubbing of the skin before blood sampling can diminish such differences. In the fasting state, the BG values at the fingertip and at the forearm were similar. However, during rapid increase in glucose, BG values at the fingertip were consistently higher than at the forearm. During rapid decrease in glucose, lower BG values were recorded at the fingertip. At the forearm, BG was delayed by a median of 35 minutes in relation to the fingertip. Rubbing of forearm skin decreased the observed differences but with a large intraindividual and interindividual variability. There were no obvious device-specific differences (three different meters were tested). The authors conclude that to avoid risky delays of hyperglycemia (high blood glucose) and hypoglycemia (low blood glucose) detection, BG monitoring at the arm should be limited to situations in which ongoing rapid changes in BG can be excluded. 2 figures. 1 table. 21 references.
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Short-Term, Delayed, and Working Memory Are Impaired During Hypoglycemia in Individuals with Type 1 Diabetes Source: Diabetes Care. 26(2): 390-396. February 2003. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: This article reports on a study undertaken to examine the effects of acute insulin-induced hypoglycemia (low blood glucose) on short-term, delayed, and working memory in individuals with type 1 diabetes. Performance in tests of immediate verbal and immediate visual memory was significantly impaired during hypoglycemia. The effect of hypoglycemia on working memory and delayed memory was more profound. Performance in the nonmemory tests, the Trail Making B Test, and the Digit Symbol Test also deteriorated during hypoglycemia. The authors conclude that all of the memory systems examined in the present study were affected significantly by acute hypoglycemia, particularly working memory and delayed memory. Mild (self-treated) hypoglycemia is common in individuals with insulin-treated diabetes; therefore, these observed effects of hypoglycemia on memory are of potential clinical importance because they could interfere with many everyday activities. 1 table. 46 references.
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How to Ameliorate the Problem of Hypoglycemia in Intensive As Well As Nonintensive Treatment of Type 1 Diabetes Source: Diabetes Care. 22(Supplement 2): B43-B52. March 1999. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: This article, which is based on a presentation given at a satellite symposium of the 16th International Diabetes Federation Congress, confutes the view that intensive treatment of type 1 diabetes carries the risk for more frequent episodes of severe hypoglycemia and that it is in principle not applicable to the vast majority of people with type 1 diabetes. Maintenance of long term near normoglycemia by intensive therapy largely, if not fully, prevents the onset of microangiopathic complications and delays progression of complications in people with type 1 diabetes. However, intensive therapy has been reported to increase the frequency of severe hypoglycemia. In addition, several experimental studies have shown that a few episodes of mild, recurrent hypoglycemia blunt the symptom and hormonal responses to hypoglycemia over the next few days. At present, the critical question is whether it is possible to maintain long term glycosylated hemoglobin (HbA1c) levels at less than 7 percent without increasing the frequency of severe hypoglycemia or mild, recurrent hypoglycemia. The answer is that it is possible to ameliorate the problem of hypoglycemia in intensive and nonintensive treatment of type 1 diabetes. The key factors are using a physiological model of insulin replacement and educating patients to determine insulin dose based on blood glucose monitoring and eating patterns. Unawareness of hypoglycemia should be suspected whenever HbA1c is less than 6.0 percent and the patient does not report autonomic symptoms when the blood glucose level is less than 3.0 mmol/L. Patients who are unaware should be treated with a short term program of meticulous prevention of hypoglycemia, which reverses the abnormalities of responses to symptoms, hormonal counterregulation, and brain cognitive function. In turn, reversal of these abnormalities decreases the risk of severe hypoglycemia. A program of meticulous prevention of hypoglycemia does not result in loss of long term near normoglycemia; that is, it is compatible with the glycemic targets of intensive therapy. 6 figures. 3 tables. 44 references. (AA-M).
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Hypoglycemia and Driving Performance (editorial) Source: Diabetes Care. 23(2): 148-149. February 2000. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: This editorial addresses the issue of hypoglycemia and driving performance by discussing a study that investigated driving impairment during progressive hypoglycemia. The study found that, for some people with diabetes, hypoglycemia that occurred while operating a driving simulator was associated with decrements in performance. In addition, many subjects took no corrective action even when they were able to recognize that their blood glucose was in the hypoglycemic range. Attempts to identify which subjects were most at risk of hypoglycemia induced driving impairments failed to implicate a history of recent severe hypoglycemia, exposure to low blood glucose in the preceding 48 hours, or the insulin regimen being used. The editorial contends that the results of the study will have an impact on people who have diabetes and who are at high risk of developing unpredictable disabling hypoglycemia by making it difficult for them to retain their driving licenses. 20 references.
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Hypoglycemia and Driving Performance: A Flashing Yellow Light? (editorial) Source: Diabetes Care. 23(2): 146-147. February 2000. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: This editorial comments on a study that investigated driving impairment during progressive hypoglycemia. The study found that, for some people with diabetes, hypoglycemia that occurred while operating a driving simulator was associated with decrements in performance. In addition, many subjects took no corrective action even when they were able to recognize that their blood glucose was in the hypoglycemic range. The editorial states that the results of this study might be interpreted to affirm the view that people who have type 1 diabetes are a potential liability to the public welfare while driving. The editorial contends that such an interpretation would be erroneous and would have a significant negative impact on millions of people who have diabetes. Of concern is the possibility that the observations made in the study would be used to adversely affect the driving privileges of people who have diabetes. The editorial urges caution in interpreting the data and argues that there is little evidence suggesting an increase in traffic accidents among people who have diabetes. Therefore, the editorial asserts that the burden of diabetes should not be increased by aggressively seeking to regulate the driving privileges of people who have diabetes. 12 references.
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Oral Hypoglycemic Drugs for Gestational Diabetes (editorial) Source: New England Journal of Medicine. 343(16): 1178-1179. October 19, 2000. Summary: This editorial comments on the use of oral hypoglycemic drugs for the treatment of gestational diabetes. Early use of first generation sulfonylurea drugs was not effective, as many women delivered infants with profound and prolonged hyperinsulinemic hypoglycemia. The observation that sulfonylurea drugs could cross the placenta and stimulate fetal insulin secretion was another cause for concern about their use in pregnancy. The risk of late fetal death for women with gestational diabetes is another concern that has been debated. Lastly, there has been concern about the possibility of congenital malformations in women taking sulfonylurea drugs during pregnancy. However, a recent randomized, controlled trial comparing the sulfonylurea drug glyburide with traditional insulin therapy found that only 4 percent of women in the glyburide group failed to achieve adequate blood glucose control. In addition, there was no evidence of any of complications resulting from fetal or neonatal hyperinsulinemia due to transplacental passage of the drug. The editorial considers the implications of these findings for clinical practice. 10 references.
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Hypoglycemia and Employment-Licensure Source: Diabetes Care. 23(Supplement 1): S109. January 2000. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: This position statement presents the position of the American Diabetes Association on the employment and licensure of people who have diabetes. Although significant medical and technological advances have been made in managing diabetes, discrimination in employment and licensure of people who have diabetes still occurs. The greatest concern about people who have diabetes may be that hypoglycemia will cause sudden unexpected incapacitation. However, hypoglycemia usually occurs gradually and is generally associated with typical warning signs. Symptoms can be
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countered by eating carbohydrates. If warning signs are absent or ignored, more severe hypoglycemia may lead to an alteration of mental function. However, most people who have diabetes do not suffer severe hypoglycemia. This condition does not occur in people who require only medical nutrition therapy and exercise to manage their diabetes. In addition, hypoglycemia is rare in people treated with oral hypoglycemic agents. Thus, most people who have diabetes can manage their condition in such a way that there is a minimal risk of incapacitation from hypoglycemia. 1 reference. •
Serum ACE Predicts Severe Hypoglycemia in Children and Adolescents With Type 1 Diabetes Source: Diabetes Care. 26(2): 274-78. February 2003. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: This study investigated whether risk of severe hypoglycemia is related to serum (S) ACE (a genotype) level during intensive treatment in children with type 1 diabetes. The study included a cohort of 86 patients with intensively treated type 1 diabetes. Severe hypoglycemia (low blood glucose) was correlated to S-ACE. Patients with S-ACE at the median level of above reported a mean of 3.0 yearly events of severe hypoglycemia compared with 0.5 events in patients with S-ACE lower than the median. Of the patients with an S-ACE at the median level or above, 27 (61 percent) reported severe hypoglycemia, compared with 17 (40 percent) patients with an S-ACE lower than the median. Insulin dose, HbA1c (glycosylated hemoglobin, a measure of blood glucose over time), age, onset age, duration, C-peptide, and sex did not differ between these two groups. The authors conclude that the elevated rate of severe hypoglycemia among patients with higher A-ACE suggests, among other factors, that a genetic determinant for severe hypoglycemia exists. Further evaluation is needed before the clinical usefulness of this test can be elucidated. 1 figure. 2 tables. 34 references.
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Self-Treatment of Hypoglycemia While Driving Source: Diabetes Research and Clinical Practice. 54(1): 17-26. 2001. Summary: While it is known that progressive hypoglycemia (low blood glucose levels) from diabetes can lead to neuroglycopenia (low enough levels of blood glucose to have an impact on the nervous system), which impairs driving, it is not clear what contributes to the patient's detection and subsequent self-correction of hypoglycemia related driving impairments. This article reports on a study of drivers with type 1 diabetes mellitus that compared who did and did not engage in self treatment during experimental hypoglycemia driving on measures of physiology and psychology. The 38 drivers drove a sophisticated driving simulator during euglycemia (normal levels of blood glucose) and progressive hypoglycemia. Subjects were continually monitored for driving performance, EEG activity, and whether they self treated with a glucose drink. For the four weeks prior to this hospital study, subjects participated in a field study. Using a hand held computer just prior to routine self measurements of BG, subjects rated neurogenic and neuroglycopenic symptoms and made judgements about BG level and ability to drive. Results showed that drivers who did and who did not self-treat did not differ in terms of their pre hospital exposure to hypoglycemia, their depth and rate of BG fall during experimental testing, or their epinephrine response to hypoglycemia. Subjects who self treated detected more neurogenic and neuroglycopenic symptoms than those who did not self treat. They also experienced less EEG defined neuroglycopenia during the progressive hypoglycemic drive as compared to those who
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did not self treat. Perceived need to self treat and EEG parameters correctly classified 88 percent of those who did treat from those who did not self treat. Further, subjects who self treated were more aware of hypoglycemia and when not to drive while hypoglycemic in the field study. The authors conclude that there is a narrow window between a patient's detection of hypoglycemic symptoms and the need to self treat, and neuroglycopenia, which impairs self treatment. Consequently, drivers with type 2 diabetes should be vigilant for signs of hypoglycemia and driving impairment (e.g., trembling, uncoordination, visual difficulties) and encouraged to treat themselves immediately when they suspect hypoglycemia while driving. 8 figures. 1 table. 30 references.
Federally Funded Research on Hypoglycemia The U.S. Government supports a variety of research studies relating to hypoglycemia. 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 hypoglycemia. 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 hypoglycemia. The following is typical of the type of information found when searching the CRISP database for hypoglycemia: •
Project Title: ALPHA AND BETA CELL FUNCTION IN NORMAL AND DIABETIC MAN Principal Investigator & Institution: Gerich, John E.; Professor of Medicine; Medicine; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2002; Project Start 01-DEC-1986; Project End 31-DEC-2002 Summary: (Adapted from Applicant's Abstract): Hypoglycemia is a common and potentially serious problem for diabetic patients regardless of whether they are treated with insulin or oral agents. Conventional risk factors (wrong insulin doses, skipped or delayed meals, exercise) explain only a small percentage of episodes. However, hypoglycemia unawareness and abnormal glucose counterregulation have recently been identified as likely explanations for many cases. The overall goal of this grant is to delineate the mechanisms responsible for hypoglycemia unawareness and for abnormal glucose counterregulation in diabetic patients. The Specific Aims of the grant application are: A) To establish the mechanisms responsible for hypoglycemia unawareness in insulin dependent Type I diabetes. The investigators will; 1) establish the normal threshold for induction of hypoglycemia unawareness by hypoglycemia and test the hypothesis that in diabetic patients the threshold is reduced; 2) test the
2 Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).
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hypothesis that hypoglycemia unawareness in diabetic individuals involves diminished beta adrenergic sensitivity; 3) test the hypothesis that hypoglycemia per se reduces beta adrenergic sensitivity; 4) test the hypothesis that there are two types of hypoglycemia unawareness - an acute reversible type due to recurrent hypoglycemia and another chronic irreversible type related to duration of diabetes, possibly representing an encephalopathic complication of diabetes. B) To assess the mechanisms responsible for impaired glucose counterregulation in noninsulin dependent diabetes mellitus. The investigator will test the hypotheses that 1) reduced glucagon responses are due to increased plasma free fatty acid levels; 2) that increased catecholamine responses are secondary (e.g. compensatory) to reduced glucagon responses; 3) that increased catecholamine responses are in part the result of poor metabolic control; 4) that subnormal increase in glucose production during hypoglycemia results from impaired glucagon responses; 5) that enhanced suppression of glucose utilization results from the effects of increased catecholamine responses on muscle; and 6) that increased muscle glycogenolysis provides gluconeogenic precursors and promotes the compensatory increase in glucose production observed during hypoglycemia. To achieve these aims the investigator will use a combination of glucose clamp, isotope and limb balance techniques in conjunction with pharmacologic interventions in normal volunteers and in research subjects having either Type I or Type II diabetes. Better understanding of the pathogenesis of hypoglycemia unawareness and abnormal glucose counterregulation should make treatment of diabetes safer and improve the chances of achieving optimal glycemic control. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ANGIOGENESIS FACTORS AND CEREBRAL ISCHEMIA Principal Investigator & Institution: Greenberg, David; Professor; Buck Institute for Age Research Novato, Ca 94945 Timing: Fiscal Year 2001; Project Start 30-SEP-1998; Project End 31-MAY-2002 Summary: Little is known about the role of Angiogenesis--the sprouting of new capillaries from existing blood vessels--in the natural history of cerebral ischemia, and its therapeutic potential in stroke is largely unexplored. The broad, long-term objective of this project is to identify mechanisms of angiogenesis in cerebral ischemia that can be adapted for therapeutic purposes. The hypotheses to be tested are: (A) Hypoxia can induce the expression and release of vascular endothelial growth factor (VEGF) in cells of the CNS; (B) Hypoxia and VEGF can stimulate the proliferation of cerebral capillary endothelial cells; (C) Ischemia and VEGF can induce angiogenesis in brain; and (D) Cerebral angiogenesis induced by ischemia or by VEGF can improve histological outcome following ischemic stroke. The specific aims are: 1. Determine the mechanisms through which hypoxia induces the expression of VEGF in neural and astroglial cells, using primary cultures from rat cerebral cortex to evaluate the relative involvement of neurons and astroglia, the role of hypoxia, hypoglycemia and glutamate, the involvement of heme proteins and hypoxia-inducible factor 1, and the level (transcriptional, post-transcriptional, or both) at which the induction of VEGF expression occurs. 2. Investigate how hypoxia stimulates VEGF receptor-mediated angiogenesis in primary cultures of endothelial cells from rat brain microvessels, by examining the effect of hypoxia, hypoglycemia, and hypoxia-conditioned medium on VEGF receptor expression, VEGF receptor-mediated signal transduction (autophosphorylation and calcium mobilization), and VEGF receptor-mediated endothelial cell proliferation. 3. Establish how cerebral ischemia induces VEGF expression, VEGF receptor expression, and angiogenesis, using the suture model of
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temporary middle cerebral artery occlusion in the rat. 4. Evaluate whether angiogenesis induced by prior focal ischemia or by administration of VEGF can decrease the size of cerebral infarcts in the same model. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ANS HYPOGLYCEMIA INDUCED GLUCAGON SECRETION IN DIABETES Principal Investigator & Institution: Havel, Peter J.; Nutrition; University of California Davis Sponsored Programs, 118 Everson Hall Davis, Ca 95616 Timing: Fiscal Year 2001; Project Start 26-APR-1997; Project End 31-MAR-2002 Summary: (Adapted from applicant's abstract): The objective of the studies outlined in this proposal is to investigate four fundamental aspects of the physiology and pathophysiology of autonomic regulation of glucagon secretion during hypoglycemia in nondiabetic animals and in animal models of diabetes. Hypoglycemia is a common and serious complication of insulin-treated diabetes mellitus in humans which limits the ability to attain improved glycemic control. The Diabetes Control and Complications Trial found a dramatic decrease of diabetic retinopathy and nephropathy with intensive therapy, but at a cost of a three-fold increase of severe hypoglycemia. Increased secretion of glucagon is a primary factor for recovery from insulin-induced hypoglycemia in nondiabetic humans. Activation of the autonomic nervous system has been demonstrated to make an important contribution to hypoglycemia-induced glucagon secretion in several species including dogs and rats, however, the role of the autonomic nervous system in humans is controversial and experiments of this type in nonhuman primates as models of human physiology have not been previously conducted. In diabetic humans, the glucagon and certain autonomic responses to hypoglycemia are often impaired. The etiology and time of onset of this impairment is poorly understood. Potential factors that may be involved include, but are not limited to, hypoglycemia-associated autonomic failure and autonomic neuropathy. Autonomic and glucagon responses to hypoglycemia are also known to be impaired in some animal models of diabetes, including diabetic rats, although few mechanistic studies have been conducted to examine the underlying etiology, nor has it been determined if pharmacological interventions can to prevent or decrease the counterregulatory defects. To address these deficits in the understanding of t he regulation of hypoglycemiainduced glucagon secretion: 1) Experiments will be conducted to examine the autonomic contribution to hypoglycemia-induced glucagon secretion in a nonhuman primate (rhesus monkeys) in the absence of diabetes. 2) To define the timing of the onset of impaired autonomic activation and glucagon secretion during hypoglycemia in rhesus monkeys with chemically-induced (streptozotocin) diabetes and the effects of different levels of metabolic control on the deficits. 3) A series of mechanistic studies will conducted in streptozotocin diabetic rats to investigate whether defects in of autonomic activation or reduced A-cell secretory responses to autonomic stimulation could contribute to impaired glucagon secretion and to determine the effects of different treatment regimens, designed to maximize chronic hyperglycemia or induce antecedent hypoglycemia, on autonomic responses and glucagon secretion. 4) Autonomic and glucagon responses to hypoglycemia will be examined in streptozotocin diabetic rats treated with pharmacologic agents that have been shown to ameliorate neural dysfunction in diabetic rats. Collectively, these experiments will lead to greater understanding of the pathophysiology and treatment of impaired hypoglycemic counterregulation in diabetes and the greater use of animal models for this area of investigation.
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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: AUTONOMIC CARDIOVASCULAR REGULATION Principal Investigator & Institution: Robertson, David H.; Professor of Medicine, Pharmacology And; Medicine; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2002; Project Start 20-SEP-1997; Project End 31-JUL-2007 Summary: (provided by applicant): The autonomic nervous system is the crucial link between the brain and the cardiovascular system. It is the final common pathway by which central disturbances whether initiated by exogenous psychological or physical stress, or endogenous biochemical or structural perturbation are translated into alterations in cardiac and vascular function. There is compelling evidence that disordered autonomic engagement of the heart and vasculature contributes importantly to many forms of cardiovascular disease: arrhythmias, sudden death, hypertension, syncope, myocardial infarction, and stoke. The goal of the Program is to achieve better understanding of how the brain exerts control over the autonomic nervous system and how the latter expresses that control onto effector tissues, through the integrating theme of autonomic cardiovascular regulation. The rationale for the Program is the tightly coordinated testing of hypotheses addressing autonomic modulation of cardiovascular function in health and disease. Component projects address central and peripheral autonomic mechanisms, employing both integrated and reductionist approaches. The roles of specific gene products (the norepinephrine transporter), and afferent (baroreflex), efferent (pure autonomic failure and multiple system failure) endocrine (hypoglycemia, exercise) and vascular (nitric oxide) mechanisms are examined. The programmatic approach will facilitate the bidirectional transfer of information between the laboratory and the clinic because it brings together investigators with a wide range of skills who have a track record of discovering new fundamental knowledge and applying it to the creation of practical improvement in health. The Program should lead directly to improved therapy in cardiovascular disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: AUTONOMIC DIABETIC NEUROPATHY IN MICE Principal Investigator & Institution: Mobbs, Charles V.; Associate Professor; Neurobiology; Mount Sinai School of Medicine of Nyu of New York University New York, Ny 10029 Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 31-AUG-2005 Summary: Impairments in autonomic function are a major complication of diabetes. The autonomic nervous system involves complex interactions between central neurons and peripheral ganglia. In particular, hypothalamic and brainstem neurons sensitive to glucose and nutritional status play a critical role in regulating the autonomic nervous system. Glucose-sensitive hypothalamic neurons appear to sense glucose through a beta cell-like mechanism. A subset of hypothalamic and brainstem neurons, like beta cells and peripheral neurons but in contrast to other central neurons, are highly sensitive to deleterious effects of and glucose derivatives. Thus some diabetes-induced impairments in autonomic activity may be due to diabetes-induced damage to these glucose-sensitive hypothalamic and brainstem neurons. The proposed studies will characterize effects of diabetes on hypothalamic and brainstem neurons, including effects of diabetes on (i) regulation of key gene products (POMC and CART) thought to be produced by glucosesensitive neurons; (ii) the ability of these neurons to sense glucose and nutritional status;
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(iii) structural impairments and possible loss of these neurons. In addition, the proposed studies will assess the correlation between hypothalamic and brainstem impairments and impairments in autonomic ganglia, the vagus nerve, and sympathetic function (regulation of temperature, heart rate, and counterregulatory responses to hypoglycemia). Finally, the proposed studies will assess the role of non-enzymatic glycation in diabetes-induced impairments observed in Studies I and II. Since diabetic neuropathy is thought to entail reversible, presumably metabolic, impairments, and irreversible, presumably structural, impairments, the present study will distinguish between reversible and irreversible impairments by comparing effects of uncorrected diabetes, diabetes corrected with intensive insulin therapy, and diabetes corrected with islet transplants. The present study should clarify the mechanisms and significance of glucose-sensitive hypothalamic and brainstem neurons in autonomic diabetic neuropathy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BLOOD GENOMICS OF ANTICONVULSANT EFFICACY IN CHILDREN Principal Investigator & Institution: Glauser, Tracy A.; Children's Hospital Med Ctr (Cincinnati) 3333 Burnet Ave Cincinnati, Oh 45229 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): The selection of anticonvulsant (AED) therapy for patients with epilepsy is based on the patient's seizure type and AED side effect profile. Since significant individual variation exists in the response to therapy, the ability to identify, either prior to or early in therapy, individuals who will attain long-term seizure freedom with a specific AED would represent a significant advance in epilepsy pharmacotherapy. We propose that the genomic expression of white blood cells prior to or just after drug administration will identify individuals likely to attain seizure freedom. Our preliminary data shows: (1) seizures, stroke, hypoglycemia and hypoxia produce characteristic changes of gene expression in the blood of rats 24 hours later, (2) single seizures produce different changes in gene expression in the blood of adult patients 24 hours later, and (3) valproic acid and carbamazepine monotherapy in children with epilepsy produces changes of gene expression in blood leukocytes that are different for each drug and different from controls. This study will determine if there is a blood genomic pattern associated with AEDs and their efficacy. The aims of this study will be to: (1) Determine if there are unique whole blood genomic expression patterns in children with epilepsy experiencing seizure freedom six months after the initiation of oxcarbazepine or valproic acid; (2) Determine whether there is a pattern of gene expression in whole blood prior to treatment that correlates with seizure freedom at one or six months of therapy; (3) Determine if there is a pattern of gene expression in whole blood at one month of therapy that correlates with seizure freedom at six months of therapy. The hypotheses are: (1) The blood genomic expression patterns in children with epilepsy treated with valproic acid and oxcarbazepine will differ from each other and will differ from the blood samples prior to therapy (2) The blood genomic expression patterns in leukocytes prior to therapy or after one month of therapy will predict which patients will attain seizure freedom from oxcarbazepine or valproic acid therapy. We will study whole blood total RNA using the new human U133 Affymetrix oligonucleotide microarrays that assess over 39,000 transcripts. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: BLOOD-BRAIN BARRIER NUTRIENT TRANSPORT Principal Investigator & Institution: Simpson, Ian A.; Professor; Neuroscience and Anatomy; Pennsylvania State Univ Hershey Med Ctr 500 University Dr Hershey, Pa 17033 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2007 Summary: (provided by applicant): The overall objective of this research proposal is the investigation of the regulation of nutrient transport across the blood-brain-barrier (BBB). The functional site of the BBB is the microvascular endothelial cell and transport of any substance into, or out of, the brain occurs at the luminal (blood-facing) and abluminal (brain-facing) membranes of this polarized cell. The central hypothesis to be tested is that nutrient transport across the BBB is regulated through the cooperative activity and interaction between the specific luminal and abluminal transport systems, combined with a dynamic intracellular pool of transport proteins. We will test this hypothesis for transport systems vital to cerebral metabolism: glucose transport via the facilitative transporter protein, GLUT1, and iron transport via the transferrin receptor and the divalent metal transporter, DMT1. The polarity of transport across cells in the periphery has been described for these systems and will be used to predict potential mechanisms in the brain. We will extend the well-characterized bovine microvessel fractionation procedure for the isolation of luminal, abluminal, and intracellular membrane fractions to determine levels and activities of the respective transporters in each fraction to support/refute the predictions. The Specific Aims are: 1) the complete characterization of the microvessel fractionation with specific attention to the fractions of the intracellular compartment; 2) the determination of structure/function relationships for GLUT1 in luminal, abluminal, and endosomal fractions; 3) the mechanism of regulation of iron transport across the BBB; and 4) the adaptation of these studies to the rat for the analysis of the effects of diabetes, hypoglycemia, as well as the genetically determined defect in iron transport in the Belgrade rat. The strength of this proposal is the availability of sufficient tissue from the bovine microvessel preparation to reliably determine activity and structure/function relationships for both of these transport systems within each compartment. The application of this information to studies in the rat, both in a miniaturized microvessel fractionation and in situ, will provide further information on the response to situations of altered metabolism, such as diabetes and hypoglycemia. Taken together these studies will provide new information on the regulation of transport across the BBB and will further our understanding of nutrient and drug delivery to the brain Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: BRAIN ENERGY METABOLISM AND HYPOGLYCEMIA Principal Investigator & Institution: Boyle, Patrick J.; Associate Professor of Medicine; Internal Medicine; University of New Mexico Albuquerque Controller's Office Albuquerque, Nm 87131 Timing: Fiscal Year 2001; Project Start 06-APR-1999; Project End 31-MAR-2004 Summary: The brain is an obligate glucose consumer and is unable to synthesize or store more than a few minutes of glucose for use during hypoglycemia. Normal subjects who experience recurrent hypoglycemia have increased rates of brain glucose uptake during subsequent hypoglycemia and therefore have no need to signal for counterregulatory hormone responses to increase systemic glucose production. This alteration leads to symptomatic unawareness of subnormal glucose concentrations. In patients with type 1 diabetes this adaptation contributes to an increased risk of serious hypoglycemia
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(seizures, comas, and episodes requiring the assistance of others in order to recover). The precise mechanism by which this adaptation occurs and the time course over which it can be induced have not been elucidated. In concert with low systemic glucose concentrations, cortisol concentrations rise during hypoglycemia and may be involved in inducing an increased brain glucose uptake. Over-insulinization associated with hypoglycemia may also play a role in the development of increased brain glucose uptake and the development of hypoglycemia unawareness. Each of the aforementioned issues will be addressed in normal man in experiments planned for the initial years of this proposal. Past experiments at the University of New Mexico have demonstrated that rates of brain oxygen utilization fail to decrease during hypoglycemia despite significant reductions in whole brain glucose uptake. Two possible mechanisms seem tenable: 1) that the amount of glucose metabolized anaerobically decreases and/or 2) alternate fuels like lactate, ketones or glutamate are oxidized instead of glucose. Experiments utilizing uniformly labeled 13C-glucose kinetics and determining the rate of appearance of uniformly labeled 13C-lactate in cortical venous effluent will assess whether or not rates of anaerobic glycolysis decrease during hypoglycemia. Also, since the brain may have the capacity to consume lactate or ketones during hypoglycemia, kinetic modeling utilizing stable isotopes of these potential fuels will be completed to assess their use as alternate fuels. These studies will help define basic brain metabolism pertinent to over 1 million patients with type 1 diabetes. Better metabolic control, the key to the prevention of long-term complications of diabetes, will thus become more achievable. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BRAIN GLUCOSENSING NEURONS IN HEALTH AND DIABETES Principal Investigator & Institution: Levin, Barry E.; Professor and Acting Chair; U.S. Dept/Vets Affairs Med Ctr(E Orange) Affairs Medical Center East Orange, Nj 07019 Timing: Fiscal Year 2001; Project Start 01-JUN-1998; Project End 31-MAY-2005 Summary: The brain requires glucose for its normal physiologic function. It has evolved glucosensing neurons which both sense and regulate peripheral glucose metabolism and energy homeostasis. Glucose responsive (GR) neurons increase their firing rate as ambient glucose levels rise whereas glucose sensitive (GS) neurons lower their firing rate as glucose levels rise. Our previous studies have identified some of the physiologic functions of these neurons and their responses to pathological states such as type 1 and 2 diabetes mellitus. This proposal will continue those studies to further delineate the function of these neurons in health and disease. The specific aims follow 2 hypotheses. Hypothesis I: Glucosensing neurons represent a unique class of sensor-integratoreffector neurons involved in the regulation of energy homeostasis. Specific Aim I: Use Ca+2 imaging combined with single cell polymerase chain reaction (SC-PCR), as well as in situ hybridization and immunocytochemistry with c-fos expression, to characterize arcuate (ARC), ventromedial nucleus (VMN) and substantial nigra (SN) GR and GS neurons by their response to and/or expression of components of the glucosensing mechanism, glucose, sulfonylureas, potassium channel openers, neuropeptides and neurotransmitters. Specific Aim II: Characterize the response of SN DA neurons to systemic hyper- vs. hypoglycemia using microdialysis. Specific Aim III: Use Ca2+ imaging with SC-PCR, in situ hybridization plus immunocytochemistry and microdialysis to characterize the effects of type I and type II diabetes on the molecular and functional properties of glucosensing neurons. Hypothesis II: Because ARC GR neurons use glucose as a signaling molecule acting at the KATP channel to sense glucose, they are selectively vulnerable to conditions which limit energy substrates as a
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source of intracellular ATP and to toxins that selectively target GR neurons. Specific Aim IV: Verify that a single bout of hypoglycemia produces apoptosis in ARC neurons using other markers of apoptosis. Then demonstrate the phenotype of apoptotic cells and that functional markers of ARC glucosensing (c-fos expression to systemic hyper- or hypoglycemia) are attenuated in such animals. Finally, show that these changes cannot be prevented by lactate or pyruvate. Specific Aim V: Demonstrate that brain glucosensing neurons are the target of toxins known to destroy pancreatic beta-cells (alloxan) and ARC neurons (gold thioglucose) using molecular and functional tests. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BRAIN TRAUMA ASSESSMENT SYSTEM Principal Investigator & Institution: Sewell, John M.; Active Signal Technologies, Inc. 13025 Beaver Dam Rd Cockeysville, Md 21030 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2004 Summary: (provided by applicant): With over 1.5 million persons suffering head injury annually in the U.S., and approximately 50,000 dying from these injuries, a need exists for early direct assessment of brain injury. Currently, injuries must be inferred from Glascow Coma Scores (GCS), low blood pressure, and/or low pulse oximetry, but there is no direct method of measuring brain condition at the scene. Active Signal proposes to test a small, portable, hand-held device to perform non-invasive measurements of brain injury, allowing direct assessment of injury even with lack of patient responsiveness. Thus, brain injury will be distinguished from low CGS caused by drugs, alcohol and hypoglycemia, and the information used for triaging and even early intervention. The brain trauma assessment system (BTAS) is modeled on one that has successfully identified neurological status on >150 trauma patients at the University of Maryland Shock Trauma Center (STC). Here, EMTs will use the BTAS on patients at the scene of injury and during transport. The measurements will be compared to the diagnosis upon admission to the STC to evaluate the device's sensitivity and specificity. Active Signal will make adjustments to accommodate demands of the EMS environment in preparation for a broad study in Phase II. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: RESPONSES
CENTRAL
GLP-1
SYSTEMS
IN
COUNTER
REGULATORY
Principal Investigator & Institution: Elmquist, Joel K.; Associate Professor; Beth Israel Deaconess Medical Center St 1005 Boston, Ma 02215 Timing: Fiscal Year 2001; Project Start 15-MAR-2001; Project End 31-JAN-2003 Summary: Intensive therapy is essential to optimize glucose control in insulindependent diabetes mellitus (IDDM). However, avoiding hypolglycemia is a major challenge for the management of IDDM. The central nervous system monitors glucose levels and coordinates a counter regulatory response during periods of hypoglycemia. However, the mechanism(s) and central pathways that underlie the counter regulatory response are not understood. Our preliminary findings suggest central glucagon-like peptide 1 (GLP-1) systems regulate sympathetic outflow and are involved in regulating CNS responses to insulin-induced hypoglycemia. We hypothesis that the action of GLP1 systems are fundamental in the coordinated endocrine and autonomic counter regulatory responses during hypoglycemia. In this proposal, we outline experiments designed to characterize the neuroanatomic mechanisms by which leptin and serotonin systems interact to regulate food intake. First, we will determine the effect of peripheral
22
Hypoglycemia
and central injections of GLP-1R agonists and antagonists on activating the sympathoadrenal and blood pressure responses. Next, using retrograde tracing and in situ hybridization, we will determine if subpopulations of GLP-1 sensitive neurons in hypothalamus and brainstem innervate sympathetic preganglionic neurons in the interomedial lateral cell column in the (IML) spinal cord. Third, using micro injections into selected brain regions, we will determine the sites in the brain that respond to GLP1 resulting in increased blood pressure and activation of adrenal catecholamine secretion. Fourth, using central injections of GLP-1 receptor antagonists we will determine the effect of central antagonism of GLP-1Rs on the counter regulatory responses to hypoglycemia. Finally, using GLP-1R-/- mice and mine over expressing GLP-1 receptor agonists, we will determine the effects on the coordinated counter regulatory responses following insulin-induced hypoglycemia in GLP-1R knockout mice and EXN-4 over expressing transgenic mice. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CENTRAL MECHANISMS
NERVOUS
SYSTEM
COUNTERREGULATORY
Principal Investigator & Institution: Jacobson, Lauren; Assistant Professor; Pharmacology & Neuroscience; Albany Medical College of Union Univ Union University Albany, Ny 12208 Timing: Fiscal Year 2003; Project Start 01-JAN-2003; Project End 31-DEC-2004 Summary: (provided by applicant): Hypoglycemia unawareness and counterregulatory failure are serious and life-threatening drawbacks to the use of intensive insulin therapy to control type 1 diabetes. Adrenomedullary epinephrine secretion is one of the most rapidly effective and readily preserved defenses against hypoglycemia. Elucidating neural pathways underlying the regulation of counterregulatory responses, and of epinephrine in particular, will aid in designing therapies to combat hypoglycemia unawareness. We have recently found that reduced brain histaminergic activity correlates with impaired counterregulation, and that inhibiting histamine synthesis decreases epinephrine responses to hypoglycemia. As part of an overall goal to identify neural mechanisms for hypoglycemia unawareness, we hypothesize that brain histamine neurons are involved in hypoglycemia-induced secretion of epinephrine, and possibly other counterregulatory hormones. We further hypothesize that manipulation of central histamine levels will aid in identifying additional neural pathways controlling these responses. To address our hypotheses, we will: (1) use specific histamine antagonists and measure counterregulatory hormones to test if hypoglycemia-induced epinephrine secretion will be selectively (a) inhibited by brain-penetrant histamine H1or H2- receptor antagonists, (b) unaffected by nonpenetrant antagonists, and (c) enhanced by increasing central histamine with the H3 autoreceptor antagonist, thioperamide. We will also (2) integrate hypoglycemic clamp techniques in unrestrained, chronically cannulated mice to test (a) the impact of streptozotocin (STZ)diabetes on the progression of counterregulatory failure and (b) the hypothesis that thioperamide-evoked increases in central histamine will reverse counterregulatory deficits induced by recurrent hypoglycemia in STZ mice. Finally (3), using brains of mice from Aims 1 and 2, we will combine in situ hybridization analysis of neuronal c-fos gene expression with histochemical analysis (histidine decarboxylase mRNA) or histamine antagonist administration, to test the hypotheses that (a) defined neural pathways, including hypothalamic histamine neurons, exhibit altered activity after recurrent hypoglycemia, and (b) experimental alterations in central histaminergic tone will reveal additional neuron populations relevant to counterregulation. These studies
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23
will provide novel information on the neuropharmacology of glucose control that may reveal therapeutic strategies to prevent hypoglycemia unawareness. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CEREBRAL HYPERKETONEMIA
ACTIVATION
IN
HYPOGLYCEMIA
AND
Principal Investigator & Institution: Pan, Jullie W.; Associate Director of Neurology and Neur; Neurology; Yeshiva University 500 W 185Th St New York, Ny 10033 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-JUL-2004 Summary: (provided by applicant): Although substantial data exist on the pathophysiology of hypoglycemia, relatively less work has examined how human cerebral functional activation is modulated by hypoglycemia. However, developments in vivo MR spectroscopy and functional MRI provide important new avenues to evaluate the metabolic dynamics of functional activation. This application proposes to assess the (patho)physiology of functional activation in euglycemia and hypoglycemia (insulin induced vs. fasting induced), and to examine the effects from ketones. In particular, in this application we hypothesize that ketones can provide substrate for cerebral activation, and to that extent, can be evaluated through the dynamics of lactate generation and extent of fMRI activation. These studies will be performed in both normal control and type 1 diabetic subjects. This is an R21, rather than a RO1 application because although recent data from Amiel et al and Veneman et al have shown that ketones can improve neurological symptomatology and cognitive performance in hypoglycemia, we do not know how ketones contribute to the metabolic physiology of functional activation. In some aspects, the hypothesis of ketones being directly contributing to functional activity is risky, because of the models suggesting that glucose is an obligate fuel. However, much existing imaging data (PET and MR) can be consistent with the view that oxidation is an important component of cerebral activation. We believe that this proposal will provide data to determine the potential role for ketones in hypoglycemia both in normal subjects and in type 1 diabetes mellitus (T1 DM) since we believe that the problem of cerebral hypoglycemia in T1DM relates in part to how the brain is able (or not) to draw on alternate fuels in activation. Work from this proposal will provide new information that may significantly change the perception as to how the brain works, as well as provide impetus towards development of ketones as an option in the clinical management of hypoglycemia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CEREBRAL RESPONSES TO INSULIN-INDUCED HYPOGLYCEMIA Principal Investigator & Institution: Seaquist, Elizabeth R.; Associate Professor of Medicine; Medicine; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2002; Project Start 03-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): The overall goal of this project is to define the cerebral response to insulin-induced hypoglycemia. In diabetes, hypoglycemia limits our ability to achieve normoglycemia and thereby reduce the long-term complications of the disease. Recurrent episodes of hypoglycemia also lead to the clinical syndrome of hypoglycemia unawareness in which patients lose their ability to detect hypoglycemia until neuroglycopenia occurs. How the brain adapts to recurrent hypoglycemia is uncertain, but greater understanding of this process will provide insights into how we can better treat patients with diabetes. In this investigation, we will directly examine
24
Hypoglycemia
how the human brain responds to hypoglycemia in vivo using high field magnetic resonance imaging and 13C magnet resonance spectroscopy. We will take advantage of the relationship between cerebral blood flow and neuronal activation to determine if glucose sensing regions can be identified in humans and to determine if the response of the brain to hypoglycemia is altered by antecedent glycemia in diabetes. We will also determine if insulin has effects on the brain that are independent of glycemia. The hypotheses we intend to examine and the aims of the studies planned to address each hypothesis are below. Hypothesis #1: During hypoglycemia, regions of the brain with an abundance of glucose sensing neurons such as the hypothalamus, amygdala, and brainstem will increase blood flow at a higher glucose concentration than will other brain regions. Aim #1: To determine blood and brain glucose concentrations at which regional cerebral blood flow is increased during hypoglycemia. Hypothesis #2: Cerebral blood flow will increase during hypoglycemia at the same brain glucose but at different blood glucose concentration in patients with poorly controlled diabetes, patients with type 1 diabetes and hypoglycemia and in healthy volunteers.Aim #2A: To determine the blood and brain glucose concentrations at which regional cerebral blood flow increases during hypoglycemia in patients with poorly controlled diabetes and compare these values to those measured in healthy volunteers.Aim #2B: To determine the blood and brain glucose concentrations at which regional cerebral blood flow increases during hypoglycemia in patients with type 1 diabetes and hypoglycemia unawareness and compare these values to those measured in healthy volunteers. Hypothesis #3: Insulin has effects independent of glucose on cerebral blood flow.Aim #3: To determine if cerebral blood flow is altered by changes in serum insulin concentrations. Aim #4: To determine if insulin alters neuronal activation as measured event-related potentials. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CHROMIUM ANALYSIS AND DIABETES Principal Investigator & Institution: Paul, Kenneth G.; Biophysics Assay Lab, Inc. (Biopal, Inc) 80 Webster St Worcester, Ma 016031914 Timing: Fiscal Year 2002; Project Start 15-SEP-2002; Project End 31-MAR-2003 Summary: (provided by applicant): Diabetes is one of the most costly health problems in America and the seventh leading cause of death Chromium has been implicated in the regulation of insulin metabolism and a number of the signs and symptoms of diabetes are shared in common with demonstrated chromium deficiency These include impaired glucose tolerance, fasting hyperglycemia, glucosuria, hypoglycemia, elevated circulating insulin, decreased insulin receptor number, and peripheral neuropathy The Office of Dietary Supplements (ODS), the National Center for Complementary and Alternative Medicine (NCCAM), and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) have invited applications for basic and clinical studies of the role of chromium as adjuvant therapy in type 2 diabetes and/or impaired glucose tolerance Studies report that chromium supplementation may improve diabetes control but one of the major obstacles in evaluating the biological effects of chromium involves assessing chromium status by a simple, readily available analytical method BioPAL, utilizing neutron activation analysis (NAA), proposes to develop a nonradioactive, convenient, and standardized commercial assay for chromium in biological tissues and fluids free of the problems of complicated sample preparation and potential contamination encountered with presently used techniques Our long-term goal (Phase II) is to develop advanced technology to significantly, improve the lower-limits of sensitivity for chromium as compared to current methods, including current NAA methods The assessment of chromium levels and their relationship to insulin sensitivity
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25
as well as the possible value of chromium in the control of hypoglycemia and various other symptoms associated either with diabetes or related pathologies would be not only a valuable tool in research but a means for determining individual chromium levels by a routine, non-destructive and non-invasive technique Ultimately these methods could be developed into a simple kit for use by clinicians or even individuals Similar methods can be adapted for the determination of other trace metals from the same sample in a single analysis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CLONING OF A TYPE 2 DIABETES MODIFIER IN OBESE MICE Principal Investigator & Institution: Leibel, Rudolph L.; Professor and Head; Pediatrics; Columbia University Health Sciences New York, Ny 10032 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-JUL-2007 Summary: (provided by applicant): Type 2 diabetes mellitus (T2DM) affects over 5% of the US population, causing tremendous suffering with annual direct medical costs of over $100 billion. In both humans and rodents, susceptibility to T2DM in the context of obesity is powerfully influenced by genes that have not been identified. The inherent complexity of identifying such susceptibility genes in humans led us to use a biallelic system in enetically obese mice to identify candidate genes and pathways for T2DM that can then be tested in humans. In F2 progeny of a B6/DBA murine cross segregating for Lep-ob, we mapped a T2DM locus to a region of murine Chr1 (p<10[-8]), syntenic to human lq23. This mouse interval lies in the middle of, and is about 1/10th the physical size of, the human interval at lq23 repeatedly identified as containing diabetes susceptibility genes in human linkage studies. The diabetic endophenotypes of the obese F2 progeny of this cross are maintained in the genetically obese members of a B6.DBA N12 congenic line segregating about 5 Mb of DBA DNA from the mouse region 1at 86. The associated phenotypes in the congenic animals are: hypoinsulinemic hyperglycemia, elevated HbA1c, and hypoplastic/hypotrophic beta cells. We propose to systematically identify and analyze all genes in the DBA congenic interval, using informatics and molecular biological techniques that we have developed. The steps will include: 1.) accession and analysis of all DNA sequence for the B6.DBA congenic interval that will be further reduced by fine mapping. 2.) identification of all transcripts by computational techniques, confirmed by expression analysis in pooled organ RNAs. 3.) sequence comparisons between B6 and DBA to identify all non-synonymous coding variants in these transcripts. Identification and sequence comparison of canonical promoter elements in 1500 bp 5' of coding sequences. 4.) computational assessment of effects of coding and non-coding variants on secondary protein structure/function and transcription. 5.) analysis of in vivo/in vitro beta cell function and skeletal muscle insulin response at 30 and 60 days in congenic animals by interval DBA dose. 6.) based upon in vitro in vivo studies, quantitative gene expression analysis (B6 v. DBA) of selected transcripts in selected organs using quantitative PCR. 7.) in vitro analysis of the functional consequences of candidate coding and regulatory sequence variants. 8.) for the most compelling sequence variants, preparation of transgenic B6 knock-ins of the DBA alleles and assessment of the relevant diabetes phenotypes in the progeny. 9.) in over 5000 individuals who have participated in studies of T2DM linked to 1q23, examine orthologous candidate genes. If successful, this project could identify a major gene (and possibly a novel pathway) for diabetes susceptibility in the context of obesity. Such a gene could be used for anticipatory diagnosis and prevention, and the design of therapeutic agents. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Hypoglycemia
•
Project Title: CNS STRESS PATHWAYS AND THE DEVELOPMENT OF ACUTE HAAF Principal Investigator & Institution: Lattemann, Dianne F.; Research Professor; Psychology; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2002; Project Start 15-AUG-2002; Project End 31-JUL-2004 Summary: (provided by applicant): A major complication for insulin-requiring diabetic individuals is the development of Hypoglycemia Associated Autonomic Failure, or HAAF. In the acute form of the syndrome the experience of two or more bouts of hypoglycemia within a 24-hour period results in a blunting of the neuroendocnne counterregulatory response which would normally correct plasma glucose levels. This phenomenon can be modeled in non-diabetic humans and experimental animals, and appears to represent a form of 'stress adaptation'. With other stressors, repeated exposure to the same stressor results in a blunting of the neuroendocrine stress response to that stress. We have developed a rat model of HAAF and have found that, concomitant with the blunted neuroendocnne response, patterns of brain activation (reflected in expression of c-fos) are altered when rats are exposed to three (vs. one) bouts of hypoglycemia in a 24-hr period. Specifically c-fos was decreased in the paraventricular (PVN) and dorsomedial (DMH) hypothalamic areas, with no change in activation of the posterior paraventricular nucleus of the thalamus (THPVP), a region which has net inhibitory input to the PVN. We concluded that a combination of decreased stimulatory input (DMH) and unchanged inhibitory input (THPVP) to the PVN may play a significant role in the decreased neural activation of the PVN and thus decreased downstream neuroendocrine activation. In this series of studies we propose to test the roles of these two brain areas, which are important in the mediation of neuroendocnne responses to other types of stressors, in the neuroendocrine response to hypoglycemic stress and in the development of HAAF. We will reversibly inactivate the THPVP and the DMH with lidocaine or the inhibitory GABA analog muscimol and measure neuroendocnne responses to hypoglycemia, with hypothesized outcomes of reversal of HAAF or simulation of HAAF, respectively. Additionally, we will test the hypothesis that a net increase of inhibitory input at the PVN (reflected by GABAergic transmission) causes the expression of HAAF, by blocking GABAergic activity in the PVN in rats that are experiencing a third bout of hypoglycemia. Together these studies will provide new insight into the role of two stress-regulatory brain regions in the normal counterrregulatory response to hypoglycemia, and in the expression of HAAF; and they will further validate the role of the PVN in mediating counterregulation to hypoglycemia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: COGNITIVE FUNCTIONS & HYPOGLYCEMIA IN CHILDREN WITH IDDM Principal Investigator & Institution: Becker, Dorothy J.; Professor; Children's Hosp Pittsburgh/Upmc Hlth Sys of Upmc Health Systems Pittsburgh, Pa 15213 Timing: Fiscal Year 2001; Project Start 20-JUL-1993; Project End 31-MAY-2004 Summary: The objective of this study is to confirm the potentially detrimental effects of mild hypoglycemia on cognitive function in children with insulin dependent diabetes (IDDM), which has been suggested from previous work. The study is designed to explore differences between children and adults and males and females with and without IDDM. The effects of prior glycemic control will be assessed. In addition, pathophysiologic mechanisms that may be associated with cognitive changes during
Studies
27
hypoglycemia will be evaluated. A correlation between alterations in cerebral blood flow and cognitive changes during hypoglycemia will be sought. The effects of epinephrine infusion and adrenergic blockade on cognitive function and cerebral blood flow will be examined. The population to be studied will consist of 70 children and adults with IDDM and 30 adult and adolescent healthy control subjects. Attempts at improvement of glycemic control in patients with IDDM is associated with an increased incidence of hypoglycemic episodes. Mild, often unrecognized, hypoglycemia is probably far more frequent that is generally accepted. If these episodes, despite being transient, have cumulative effects, this could impair school functioning and ultimate academic achievement. If significant cognitive changes are confirmed on a large scale study of children, this potential side effect of tightened glycemic control will have to be weighed into the cost: benefit ratio of attempts to prevent the chronic complications of IDDM. Recognition of patients at risk and a better understanding of the mechanisms of cognitive changes, may allow the development of future strategies that might avoid this complication while still achieving the overall goals of diabetes therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CONTINUOUS GLUCOSE SENSORS IN YOUTH: BIOBEHAVIORAL STUDY Principal Investigator & Institution: Wysocki, Tim T.; Chief; Nemours Children's Clinic 807 Children's Way Jacksonville, Fl 322078482 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-AUG-2006 Summary: (prepared by applicant): Intensive therapy for youths with type 1 diabetes mellitus (DM) yields higher HbA1c and more frequent severe hypoglycemia (SH) than for adults. The advent of continuous glucose sensors (CGS) could yield medical and psychological benefits for these youths. The investigators submit that many patients may not realize these benefits and that psychosocial features of patients and families will affect the outcomes of adding CGS to DM therapy. To maximize the therapeutic benefits of CGS, we need clinically useful information about its glycemic and psychological effects and about psychological influences on its therapeutic utility. This information would be useful in selecting candidates for this technology and for assisting patients and families in achieving positive outcomes from its use. This application addresses four specific aims: 1.) Evaluation of the effects of 12 month?s use of a CGS device (GlucoWatch Biographer, Cygnus, Inc.) on HbA1G, the Kovatchev Low Blood Glucose Index and the frequency of severe hypoglycemia; 2.) Identification of behavioral and psychological consequence of CGS use; 3.) Analysis of psychosocial predictors of metabolic and psychological outcomes; and 4.) Evaluation of glycemic profiles of healthy youths without DM, construction of a normative glycemic profile for use in future studies and comparison of the glycemic profiles of youths with and without diabetes. Specific Aims 1 through 3 will be addressed in a randomized, controlled trial of three intensive therapy regimens that are based on different glucose monitoring methods: SMBG patients will receive current intensive therapy with four to six self-monitored blood glucose tests daily; CGS with Feedback patients will augment SMBG by using a CGS device that gives immediate glucose feedback and alarms for high, low, and rapidly falling levels; CGS without Feedback patients will augment SMBG by using the same CGS device with the feedback and alarm functions disabled. Patients and parents will complete periodic assessments of demographic factors and general and diabetes-specific psychological factors. Statistical analyses will include multivariate analyses of variance, survival analysis and individual growth modeling techniques. Specific Aim 4 will be addressed by studying a demographically similar
28
Hypoglycemia
sample of 240 healthy children and adolescents who will use the GlucoWatch Biographer without feedback for a total of 144 hours during a two-week period. The project results will enhance clinical adoption of CGS technology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: COORDINATING CENTER: GLUCOSE SENSORS IN TYPE I DIABETES Principal Investigator & Institution: Beck, Roy W.; Director; Jaeb Center for Health Research, Inc. Suite 350 Tampa, Fl 33647 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-AUG-2006 Summary: (prepared by applicant): This application is submitted in response to the RFA for a Data Coordinating Center (DCC) to serve the needs of the Type 1 Diabetes in Children Research Consortium. The objectives of this project are (1) to develop insight into the role of continuous glucose monitoring devices in the management of children with type 1 diabetes, (2) to develop a better understanding of glycemic control and hypoglycemia in children with type 1 diabetes, and (3) to gain knowledge of glucose homeostasis in children without diabetes. An ultimate objective is to develop ageappropriate treatment approaches to type 1 diabetes in children. The project is expected to include four clinical centers as well as the DCC. The role of the DCC in a multi-center project such as this one is key to its success. As it is not the purpose of the DCC application to justify the need for this research or to propose a specific protocol, this application will focus on the capabilities of the Jaeb Center to serve as the DCC for the project. The investigators will detail the approach they propose to take for the key elements of the project?s coordination, administration, and conduct. It will be apparent that the principal investigator has extensive knowledge of type 1 diabetes in children, its treatment, and the role of glucose monitoring. He will be able to provide considerable input to protocol development as a member of the Steering Committee. In essentially all areas the investigators will draw upon their experience in past and current projects to develop procedures for this study. The investigators have coordinated numerous multicenter investigator groups and have experience with all of the DCC functions and responsibilities that will be part of this project. They have been innovative in their approach to clinical trial conduct and management and have relied extensively on using the Internet to not only increase efficiency but also in many ways to enhance quality control measures. For a number of years the investigators have strived to develop a data management system that is as generic as possible so a new study can be readily added to an existing database and data management structure. This extends to web-site development in which the web-based applications the investigators have developed for their prior and current studies will serve as a template for this project. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DEPRESSION AND BRAIN STRUCTURE IN TYPE 1 DIABETES Principal Investigator & Institution: Jacobson, Alan M.; Senior Vice President; Joslin Diabetes Center Boston, Ma 02215 Timing: Fiscal Year 2002; Project Start 15-AUG-2002; Project End 31-JUL-2006 Summary: (provided by applicant): There is growing evidence that type 1 diabetes leads to an increased prevalence of depressive disorders and preliminary data suggesting that the metabolic disturbances associated with diabetes, both severe hypoglycemia and persistent hyperglycemia, lead to changes in brain structure and cognition. These findings, together with research on structural changes in the brain among depressed
Studies
29
patients without diabetes, suggest that diabetes could cause structural changes in the brain that lead to depression. No studies have evaluated mechanisms underlying the etiology of depression among patients with type 1 diabetes. Using a cross sectional research design, we propose to study six groups of subjects: All subjects (N = 180) will be ages 30-40, right-handed and matched according to age, gender and SES. Diabetic patients will have between a 15-25 year history of types of diabetes. There will be three groups of diabetic subjects without psychiatric history: 1. Well controlled (0-1 episodes of severe hypoglycemia; mean HbA1c over history of diabetes equal to or 3 episodes of severe hypoglycemia; mean HbA1c over time equal to or 9.0%; 0-1 hypoglycemic episodes). A fourth group of diabetic subjects with a history of unipolar major depression and who equally represent the glycemic control characteristics of the other three diabetic groups will also be studied. In addition, two non-diabetic control groups (history of depression; no psychiatric history) will also be studied. We will assess these patients as to brain structure, using Magnetic Resonance Imaging (MRI); depression, using the Structured Clinical Interview for DMS IV (SCID); and cognition using the Wechsler Adult Intelligence Scale III (WAIS III) and other neuropsychological tests of memory, psychomotor speed and mental efficiency. We will also evaluate medical factors (e.g., glycemic control-HbA1c; and history of severe hypoglycemia). We will examine whether: 1) structural abnormalities are more common in diabetic subjects compared to the matched community controls; 2) there is a relationship between diabetes specific medical variables, such as long-term glycemic control, and brain structure abnormalities; 3) structural abnormalities are more common in diabetic patients with a history of unipolar major depression than diabetic patients without a history of depression; and 4) the frequency of structural abnormalities in the brain among diabetic patients with a lifetime history of unipolar depression differs from the depression control group. The proposed research will, for the first time, provide evidence regarding the linkage between structural changes in the brain and depressive disorder in diabetes, and evidence about the relationship of type I diabetes and its attendant metabolic disturbances to structural changes in the brain. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DEVELOPMENT NUTRACEUTICAL
OF
AN
ANTI-DIABETES
BOTANICAL
Principal Investigator & Institution: Ilic, Nebojsa; Phytomedics, Inc. 65 Stults Rd Dayton, Nj 08810 Timing: Fiscal Year 2002; Project Start 20-SEP-2002; Project End 31-MAR-2003 Summary: (provided by applicant): This is a revised proposal for the pre-clinical development of PMI-5011, a standardized botanical extract, developed by Phytomedics Inc. and Rutgers University. PMI-5011 effectively lowers blood glucose in insulin deficient and insulin resistant animals, does not cause hypoglycemia, and is safe and non-toxic. All data suggest that PMI-5011 is an efficacious nutritional supplement for those suffering from diabetes or prediabetic conditions. Preliminary results demonstrate that PMI-5011 specifically affects hepatic gene expression in diabetic rats and promotes insulin mediated glucose uptake by muscle tissues as potential means of normalizing glycemia. Phytomedics will use the SBIR funds to complete the necessary pre-clinical investigation of PMI-5011 and to produce a sufficient supply of the standardized and optimized PMI-5011 material for the remaining preclinical and clinical testing. Phytomedics will also confirm the identity of the active ingredients of PMI-5011 and determine optimal hydroponic greenhouse methods for the source plant cultivation. Phytomedics will conduct limited clinical trials of PMI-5011 in Phase 2 of this proposal.
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Hypoglycemia
Phase 3 of this proposal will involve the full-scale commercialization of PMI-5011 with a commercial partner, using PMI-5011 exclusively supplied by Phytomedics. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DYNAMIC FEEDBACK CONTROL OF THE GH AXIS Principal Investigator & Institution: Farhi, Leon S.; Internal Medicine; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904 Timing: Fiscal Year 2001; Project Start 01-JUN-2001; Project End 31-MAY-2005 Summary: The candidate has a Ph.D. in mathematics, with a strong research background in mathematical physics, including dynamical systems, differential equations, spectral theory, geometry etc. Since 1997 he has been working on an interdisciplinary biomedical study with the University of Virginia (UVA), establishing new bioanalytical tools for modeling of blood glucose fluctuations related to hypoglycemia in IDDM. In April 1999, the candidate joined the department of Internal Medicine at UVA, working on dynamic feedback control of the growth hormone (GH) axis. The studies resulted in the creation of a new deterministic model, describing the male rat GH secretory pattern, and shaped the foundation of the present research/training application. On a research level, we propose to investigate our general hypothesis that a parsimonious feedback model can approximate the secretory pattern in both male and female rats, with the observed gender differences explained solely by parameter transitions. The model will be tested/refined using data collected by other projects and will be further extended to approximate the GH release network in the human. We believe that the results will offer new insights into the functional organization of the neuroendocrine hypothalamo-pituitary mechanisms that mediate the dynamic activity of the GH axis. On a training level, the candidate's immediate goal is to establish a sufficient background in the field of hormone pulsatility that will promote his efforts to approach analytically problems related to GH release in the rodent and human. To meet this goal, the career development plan anticipates two formally different parts. The first half of the award period includes four basic medical courses combined with supervised research. The second half is dedicated exclusively to extensive supervised research in the framework of the research plan. The proposed fouryear research/training will be performed at the UVA, a university with rich traditions and a large network of facilities supporting research and education in the life sciences. The candidate will interact extensively with outstanding scholars across multiple laboratories, which will help him to achieve the long-term goal of this award - to become an independent investigator able to apply advanced mathematics in biomedical research related to endocrinology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DYNAMIC FMRI ANALYSES OF HYPOGLYCEMIA UNAWARENESS Principal Investigator & Institution: Liu, Yijun; Psychiatry; University of Florida Gainesville, Fl 32611 Timing: Fiscal Year 2002; Project Start 15-SEP-2002; Project End 31-JUL-2004 Summary: (provided by applicant): We propose a functional MRI (fMRI) study to probe the timing and location of neuro-hormonal interaction following food ingestion in humans. The proposal presents an explorative fMRI project by developing in vivo methods to characterize brain activity during hypoglycemia induced by prolonged fasting. We will examine brain responses during a real-time transition from fasting hypoglycemia to normoglycemia attained by eating (i.e., by oral glucose intake),
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focusing on the hypothalamus and its associated neural circuits. In particular, this project underscores two novel dynamic imaging approaches for tracing the time course of brain-hormone interaction during the transition. These approaches, namely (1) temporal clustering analysis (TCA) and (2) within-condition interregional covariance analysis (WICA), are critical to the timing of neuronal events that are interacting with hormonal processes, such as glucose-insulin regulation. Modeling of both temporal and spatial information about brain-hormone interaction will be our first step toward establishing a functional marker of hypoglycemia unawareness. By the functional marker we mean noninvasively -measured neuroendocrinal signals in response to a physiological challenge, such as fasting or eating. We hypothesize that alteration of such signals is implicated in the development of hypoglycemia unawareness, as in insulindependent diabetes mellitus (IDDM) accompanied by recurrent hypoglycemia. Although the ultimate goal of this project is to directly test this hypothesis in patient population under long-term intensive insulin treatment, which may require large-scale clinical trials, the current R21 proposal aims to develop new fMRI methodology involving a small number of subjects imaged under well-controlled conditions. While functional imaging methods may reflect a departure from traditional, symptomdependent assessment of hypoglycemia unawareness (e.g., cognitive task testing or objective neurophysiological evaluation), it is still important to correlate fMRI analyses with routine clinical measurements, such as counterregulatory hormone levels by blood sampling. This correlation may provide information for delineating the neural bases about how internal biochemical signals give rise to the awareness of hunger or satiation, and for understanding the phenomenon of hypoglycemia unawareness. Two specific aims are to be accomplished in this two-year project: Aim 1. Development of a fastingeating fMRI paradigm by correlating functional imaging signal with biochemical measurement; and Aim 2. Development of both temporal and spatial reference systems for the in vivo modeling of glycemia regulation and hypoglycemia unawareness. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: OUTCOMES
DYSVASCULAR
AMPUTEES:
REHABILITATION
USE
AND
Principal Investigator & Institution: Dillingham, Timothy R.; Associate Professor; Physiology; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2001; Project Start 10-AUG-1998; Project End 31-MAY-2003 Summary: The purpose of the study is to examine the rate of hospitalization of nursing home patients. Behavioral models used in the study are based on contingency theory and resource dependence theory. Data come from a sample of residents in 30 nursing homes in five states linked to Medicare claims data, On-line Survey of Certification Automated Records (OSCAR) and Area Resource File (ARF) data. The goal is to separate the proportion of explained variation in hospitalization rates that is due to market and facility factors from the portion explained by resident characteristics. Part of the analysis will focus on two potentially avoidable causes for hospitalization: dehydration and diabetics who are admitted with a primary admission diagnoses of hyperglycemia or hypoglycemia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EVALUATION OF A NON-INVASIVE GLUCOSE MONITOR Principal Investigator & Institution: Buchert, Janusz M.; Infratec, Inc. 539 Danbury Rd Wilton, Ct 06897
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Timing: Fiscal Year 2003; Project Start 15-AUG-2003; Project End 31-JUL-2005 Summary: (provided by applicant): Sixteen million people in the United States live with the chronic disease diabetes; approximately 5 -10% are children. The seminal Diabetes Control & Complications Trial (DCCT) concluded that frequent glucose monitoring is necessary to reduce the complications of this disease. However, all glucose monitors available require invasive techniques with the most widely used method of selfmonitoring, obtaining blood from a finger stick, causing pain and discomfort which results in poor compliance. The development of a novel, hand-held, non-invasive glucose monitor will provide diabetics with the means for testing their glucose level more frequently, improving their quality of life, and reducing the costs and complications of this chronic disease. This application proposes the development, calibration and clinical validation of an advanced prototype based on a proprietary method of mid-infrared Thermal Emission Spectroscopy (TES). The method and instrument are based on the discovery that natural mid-infrared emissions, from the tympanic membrane, consist of spectral information of blood analytes. In recent years, infrared (IR) spectroscopy has emerged as a potential analytical method of choice for non-invasive glucose monitoring. The specific aims of this Phase I proposal are to develop the optical system and to integrate sensors into an ergonomic form for diabetic self-monitoring. The subsequent clinical studies are designed to demonstrate that a universal calibration for real time accurate measurements is possible for predictive results. The device will be calibrated and validated across a range of glucose concentrations from 40 to 400 mg/dL, using a total of 52 diabetic and normal subjects in hyperglycemic and hypoglycemic protocols. A trained nurse will perform the measurements. Subsequently, 19 diabetic subjects will test themselves using the hyperglycemic protocol in a full predictive study. The hypotheses will test that the intraindividual correlation coefficient of the non-invasive predicted serum glucose compared with the clinical laboratory serum glucose measurement will be greater than 0.85, and less than 1 percent of the measurements will fall outside the clinically acceptable range on the Clarke Error Grid. Successful conclusion of Phase I milestones will lead to Phase II clinical studies and modifications for younger pediatric subjects. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FETAL PANCREATIC DEVELOPMENT & INSULIN SECRETION Principal Investigator & Institution: Hay, William W.; Professor; Medicine; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007 Summary: (Provided By Applicant)The goal of this research project is to understand mechanisms regulating pancreatic development and function that are influenced by nutrients and secondary endocrine factors that augment the effects of nutrients and to focus specifically on the limited pancreatic growth and function in fetuses with intrauterine growth restriction (IUGR). We will test the hypothesis that reduced fetal nutrition from placental insufficiency will result in primary nutrient (glucose) and secondary hormonal (insulin, IGFs) deficiencies that lead to abnormal pancreatic endocrine development and function with 3 specific aims. 1. Analyze pancreatic development and function to define critical developmental periods and identify the adaptations imposed by decreased nutrient availability in the IUGR fetus. 2. Determine the effects of nutrient and hormonal deficiencies on insulin production and secretion in pancreatic endocrine cells in the IUGR fetus. 3. Test the ability to restore normal pancreatic development and function by in vivo nutrient and hormonal supplementation during critical periods of development in the IUGR fetus. The
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proposed studies will be conducted in our ovine model of IUGR produced by maternal exposure to a moderately hyperthermic environment during gestation. These fetuses develop hypoglycemia and hypoaminoacidemia and secondary deficiencies in insulin and GF concentrations in the latter third of gestation. in vivo and in vitro studies will characterize pancreatic development and function and determine mechanisms responsible for pancreatic abnormalities that are direct consequences of fetal nutrient deprivation. The studies also will provide insight into requirements for clinical interventions to ameliorate pancreatic insufficiency in IUGR fetuses and neonates, hopefully to reduce fetal and neonatal morbidity and mortality, and potentially to reduce the incidence of adult onset diseases that have been associated with low birth weight. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GAP JUNCTION BLOCKAGE ATTENUATES BRAIN ISCHEMIC INJURY Principal Investigator & Institution: Rozental, Renato; Neuroscience; Yeshiva University 500 W 185Th St New York, Ny 10033 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2005 Summary: (provided by applicant): Severe perinatal ischemia can lead to brain injury and dysfunction. Although hypoxia- and hypoglycemia-mediated loss of synaptic functions and neuronal death are major components of brain ischemia pathophysiology, effective clinical neuroprotection for this damage remains elusive. Our preliminary experiments provide support for the novel hypothesis that gap junctions, the intercellular channels that mediate electrical synchrony and metabolic cooperation between apposed cells, participate in propagation of neuronal damage and death following global ischemia in developing brain. Evidence indicates that cells injured by ischemic brain insults are linked to surrounding, less-affected cells, and that this "bystander effect" expands the volume of a brain ischemic injury over time. The overall goal of the proposed studies is to characterize the role of neuronal and astrocytic gap junction channels in propagating delayed neuronal death mediated by ischemic insults in field CA1 of the hippocampus. The broad hypotheses to be tested are that: (1) gap junction-mediated signaling can amplify the extent of ischemic injury, and (2) gap junction blockade will reduce the extent of cell death of CA1 pyramidal neurons and astrocytes following ischemia This application proposes to address these questions using both hippocampal organotypic slice cultures and in vivo studies performed in newborn rodents delivered by Caesarean-section and subjected to immediate transient global hypoxia, prior to removal from the uterus and commencement of respiration. Two complementary strategies will be used: First, molecular biological and electrophysiological techniques will evaluate the extent of ischemia-induced injury in slice cultures from wild type mice. Second, the extent of damage will be compared to mice in which the major neuronal (connexin36) and astrocytic (connexin43) gap junction proteins have been genetically reduced (Cx36-/+ and Cx43-/+) or ablated (Cx36 and Cx43 knockouts), and under conditions in which the ischemic event occurs when Cx43 and Cx36 are differentially blocked pharmacologically. These studies are expected to provide mechanistic insights into the extent of neuronal death following brain global ischemia and to have significant therapeutic application in the treatment of long-term sequelae of ischemia in perinatal brain. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GLU6PASE AND 6P2K/FBASE GENE REGULATION IN SEPSIS Principal Investigator & Institution: Maitra, Subir R.; Emergency Medicine; State University New York Stony Brook Stony Brook, Ny 11794 Timing: Fiscal Year 2001; Project Start 01-AUG-1999; Project End 31-JUL-2004 Summary: Sepsis is that critical condition of the patient which, if uncorrected, leads to death. The initial hyperglycemia seen in sepsis is followed by hypoglycemia with concomitant hyperlacticacidemia. Glucose-6-phosphatase (Glu-6-Pase) is a key enzyme in the homeostatic regulation of blood glucose concentration, which catalyses the final step in gluconeogenesis and glycogenolysis. Another important enzyme for regulation of gluconeogenesis is 6-phosphofructo-2-kinase/fructose-2,6bisphosphatase (6PF2K/FBPase), which is responsible for the production and hydrolysis of fructose-2,6bisphosphate (Fru-2,6- P2), a modulator of glycolytic to gluconeogenic flux. We have demonstrated that gene expression of Glu-6-Pase and 6PF2K/FBPase are reciprocally modulated during hyperglycemic phase of hemorrhagic shock. In this proposal, we are focusing on the regulation of expression of these two genes as models of hormonal counter-regulation during sepsis. In addition to studying the hormonal regulation of these genes in sepsis, we also propose to determine the hormonal response elements of these genes by promoter analysis. Sepsis will be induced in fasted, anesthetized rats by cecal ligation and puncture (CLP) method and will be observed for 0.5 h, 3 h, and 20 h periods. Control rats will undergo sham operation and will be observed for the same time. The liver and kidney from control and CLP rats will be freeze-clamped in liquid nitrogen and stored at -70 degrees C for future assay of glucose-6- phosphate, fructose-6phosphate, glucose-6-phosphate dehydrogenase activity, Glu-6-Pase and 6PF2K/FBPase enzyme activity and gene expression. Blood samples will be collected at the same time periods to assay glucose, corticosterone, insulin and glucagon concentration in the plasma. Relatively selective pharmacologic antagonists of hormones and cytokines will be administered prior to CLP to observe their effects on Glu-6-Pase and 6PF2K/FBPase gene expression. Hepatocytes will be isolated from control and CLP rats and will be incubated with agonists to observe their effects on Glu-6-Pase and 6PF2K/FBPase gene expression. Freshly prepared, primary cultures of hepatocytes will be transfected and then incubated with hormones and hormonal response element will be confirmed by DNA footprinting. The results of this study are essential to understand the molecular basis of deranged metabolism in sepsis. Understanding the mechanism might be useful for developing appropriate therapeutic intervention during sepsis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GLUCONEOGENESIS IN VERY LOW BIRTH WEIGHT INFANTS Principal Investigator & Institution: Sunehag, Agneta; Assistant Professor of Pediatrics; Pediatrics; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2001; Project Start 01-FEB-2000; Project End 31-JAN-2005 Summary: Improvements in the management of premature infants have resulted in a dramatic increase in their survival. Previously, nutritional management was not of high priority in very low birth weight (VLBW) infants since most died early in life. As a result, our refinement of the nutritional management of these surviving infants has lagged behind the advancements in cardio-respiratory therapy. VLBW infants are susceptible to hypoglycemia; thus, to provide sufficient calories and to prevent hypoglycemia, glucose is routinely infused at high rates (approximately 60 mumol/kg min, twice that of measured glucose turnover rates in these infants) as part of standard total parenteral nutrition (TPN) which frequently results in hyperglycemia. Like
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hypoglycemia, hyperglycemia can have significant short and long term adverse impact on their outcomes. The specific focus of the present application is to determine the individual and collective roles of the substrates provided in standard total parenteral nutrition on glucose production from glycogenolysis and gluconeogenesis (GNG) and glucose utilization. These studies will determine: a. Whether VLBW infants receiving TPN who are normoglycemic suppress their glucose production completely and those who are hyperglycemic have incomplete suppression of glucose production and/or reduced glucose utilization; b. When VLBW infants are supplied glucose at a reduced rate (17 mumol/kg min): 1. Do i.v. lipids (IntralipidR) increase GNG and glucose production and if so is this the result of providing energy for GNG through betaoxidation or providing glycerol as a 3-carbon precursor; 2. Whether glycerol increases GNG and glucose production in a dose dependent fashion in VLBW infants; 3. Whether i.v. amino acid solution (TrophAmineR) and/or the gluconeogenic amino acids, glutamine and alanine, will increase GNG and glucose production; and 4. Whether glucagon will increase GNG and glucose production from endogenous and exogenous substrate sources. The ultimate aim will be to utilize this information in designing alternative mixtures of constituents (substrates and possibly hormones) which will decrease the risk of both hypo- and hyperglycemia in these infants, by utilizing the infants' gluconeogenic pathway, while providing sufficient substrate to sustain normal growth and development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GLUCOSE MEDIATION OF NORADRENERGIC ACTIVITY IN VMH Principal Investigator & Institution: Beverly, Joseph L.; Assistant Professor; Animal Sciences; University of Illinois Urbana-Champaign Henry Administration Bldg Champaign, Il 61820 Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 31-AUG-2005 Summary: (Applicant's abstract): Circulating glucose concentration is monitored and maintained at appropriate concentrations by the central nervous system (CNS). Physiological and behavioral responses to glucose imbalances have been described, but the key mechanism by which fluctuations in glucose status are recognized and appropriate counter-regulatory responses initiated is not known. The immediate objective of the proposed research is to identify underlying neurochemical mechanisms in the ventral hypothalamus that sense changes in plasma glucose and initiate counterregulatory responses to restore glucose status. Noradrenergic activity in the ventromedial hypothalamus (VMH) has been demonstrated to influence blood glucose through effects on the autonomic nervous system, behavior, and neuroendocrine system. We have reported a consistent activation of noradrenergic systems in the VMH during hypoglycemia. The specific aims of this application are to determine the glycemic thresholds for the activation of noradrenergic systems in the VMH, to evaluate the effect of changes in interstitial fluid glucose concentrations in the VMH on noradrenergic activation, to determine if the activation of noradrenergic systems in the VMH is mediated through local intrinsic neurons within the VMH, to the effect of recurrent hypoglycemia on the noradrenergic activation in the VMH, and determine if increased levels of circulating leptin alter sensitivity of noradrenergic response to hypoglycemia. Intravenous catheters and microdialysis probes will be used to simultaneously monitor plasma glucose and concentrations of extracellular neurotransmitters in the VMH. Our hypothesis is that glucose responsive neurons in the VMH respond to changes in extracellular glucose concentrations that reflect circulating plasma glucose and activates noradrenergic inputs to the hypothalamus. The activation
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of these neurons is dynamic, so that the glycemic threshold for activating NE systems in the VMH will be altered by recurrent episodes of hypoglycemia. Further, we propose that leptin affects the sensitivity of glucose response neurons to interstitial glucose concentrations thereby altering the glycemic threshold for activation of glucoregulatory systems in the VMH. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GLUCOSE SENSORS AND HYPOGLYCEMIA IN CHILDREN WITH DM Principal Investigator & Institution: Tsalikian, Eva; Associate Professor of Pediatrics; Pediatrics; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-AUG-2006 Summary: (provided by applicant): Intensive therapy is currently accepted as the standard of care to reduce the risk of long term complication in patients with diabetes of all ages. However, intensive therapy is frequently complicated by hypoglycemia. In comparison to adults, young children and adolescents have even more lifestyle characteristics that make them prone to hypoglycemia, which then becomes a dangerous complication and a major limiting factor of intensive treatment and good diabetes control. With current home glucose monitoring capabilities it is difficult to accurately define the true incidence, duration, and severity of hypoglycemia in children with diabetes. A continuous glucose monitoring system (CGMS) has recently become available as a tool to more closely examine blood glucose patterns, by recording up to 288 glucose measurements a day (864 glucose readings over a 72 hour period). The purpose of the proposed study is to elucidate the extent of hypoglycemia and the factors that contribute to hypoglycemia in children with and without diabetes. In this descriptive study, four age groups of children will be studied: defined by children 2-6, 610, 10-14, and 14-18 years of age. Grouping by age will assure an appropriate sample of children of different ages, as well as a large prepubertal cohort. Eighteen children with diabetes will be included in each age group for a total of 72 patients with diabetes. Nine children without diabetes will serve as controls for each age group in order to study the normal physiologic glucose variability. During the four years of data collection, subjects will participate for one to three years, depending on the time of enrollment. They will be fitted with the CGMS for three days, quarterly, alternating week, and weekend intervals. Data will be obtained on the child?s medical history, blood glucose levels, genotyping, and dietary intake. Activity will be monitored by accelerometry. Cognitive functioning, school performance, behavior, and adjustment to diabetes will be measured as potential factors contributing to the risk of hypoglycemia. In summary, CGMS in children with diabetes will provide valuable information on hypoglycemia frequency and severity, and the risk factors associated with this serious complication of intensive diabetes management in children. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GLUCOSE SENSORS IN CHILDREN WITH TYPE I DIABETES Principal Investigator & Institution: Chase, Peter H.; Professor; B Davis Ctr/Childhood Diabetes; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-AUG-2006 Summary: (prepared by applicant): The specific aim of this application is to determine if glucose control can be safely improved in children with type 1 diabetes as a result of
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using continuous glucose monitoring (CGM). In an initial feasibility trial, accuracy of the two CGM devices will be compared to venous glucose levels in a Pediatric GCRC. Children with and without diabetes will spend 24 hours in the GCRC. This will also help to sort out children with diabetes (1 in 30) who have excessive skin reactions to the GlucoWatch, or who cannot tolerate subcutaneous CGM sensors. The children with diabetes will then be randomized to a feasibility three-month trial of either using the GlucoWatch Biographer or the MiniMed CGMS or serving as a control. Children will be selected for the feasibility and the two-year study who are either using intensive diabetes management or who are committed to moving toward intensive diabetes management. They must be willing to do at least four self-blood glucose monitoring (SBGM) tests each day. They will be randomized to two years of treatment, including six months of using four GlucoWatch Biographers per week (two day/two night), six months of using the MiniMed CGMS, and a six month control period. Primary end points will be change in HbA1c levels and the incidence of hypoglycemia. HbA1c levels will be determined initially and every three months, or at one and three months in the feasibility trial, with a goal of achieving HbA1c values less than seven percent. The incidence of all hypoglycemic events and of severe hypoglycemia will be compared for the three treatment groups in the three-month feasibility and the two-year longer trial. In addition, each person will serve as their own control in the longer trial as they are randomized to each of the three study groups. Secondary end points will be episodes of ketoacidosis, change in BMI, numbers of sensors used, insulin dose, use of an insulin pump, use of carbohydrate counting, number of SBGM tests done per day and changes in Fear of Hypoglycemia and Quality of Life Questionnaires. Quality of Life and Fear of Hypoglycemia Questionnaires will be used to evaluate psychological factors in both the factors in both the feasibility and the two-year trials. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GLUCOSENSING NEURONS IN EUGLYCEMIA, HYPOGLYCEMIA & HAAF Principal Investigator & Institution: Routh, Vanessa H.; Pharmacology and Physiology; Univ of Med/Dent Nj Newark Newark, Nj 07103 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-JUL-2006 Summary: (provided by applicant): This proposal investigates the effects of recurrent hypoglycemia on glucose sensing neurons in the ventromedial hypothalamic nucleus (VMN). The overall objective is to gain a clearer understanding of (a) how changes in glucose are transduced into neuronal signals, and (b) how those neuronal signals are integrated to initiate the counterregulatory response to hypoglycemia. The two hypotheses in this proposal directly address these issues. HYPOTHESIS I is that VMN glucose sensing neurons have the potential to sense impending hypoglycemia and signal for the initiation of the counterregulatory response. This hypothesis derives from our knowledge of the ability of VMN glucose sensing neurons to respond to physiologically relevant changes in extracellular glucose. HYPOTHESIS II is that VMN glucose sensing neurons receive information from and project to brain regions important to the regulation of glucose homeostasis. The first set of experiments proposed herein will define the responsiveness of physiologically relevant subtypes of VMN glucose sensing neurons over physiological glucose concentrations. We will then determine whether or how the responses are altered by recurrent hypoglycemia sufficient to induce hypoglycemia associated autonomic failure. We will also explore the cellular mechanism of glucose sensing transduction so that the mechanisms that underlie any change in responsiveness can be understood. The second set of
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experiments will provide the basis for understanding the potential integrative role of VMN glucose sensing neurons. This will be accomplished by identifying presynaptic inputs and transmitters to the VMN from other glucose sensing neurons and identifying the hypothalamic targets of VMN glucose sensing neurons. These studies will provide important information regarding the way that the brain regulates glucose homeostasis and the way that perturbations in glucose homeostasis alter these central mechanisms. This will facilitate the development of new and effective treatments for Type I diabetes mellitus and its major modern complication hypoglycemia. 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 Programs Chicago, Il 60611 Timing: Fiscal Year 2001; 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: HEPATIC INSULIN GENE EXPRESSION IN IDDM Principal Investigator & Institution: Woo, Savio L.; Professor and Director; Center for Gene Therapy & Molecular Medicine; Mount Sinai School of Medicine of Nyu of New York University New York, Ny 10029 Timing: Fiscal Year 2001; Project Start 15-SEP-1998; Project End 31-JUL-2002 Summary: Insulin-dependent diabetes mellitus (IDDM) is characterized by a severe deficiency of insulin secondary to the autoimmune destruction of pancreatic beta cells. Current treatment for IDDM includes multiple daily insulin injections and specialized regimens of diet and exercise. Occasional lapses in patient compliance can result in acute episodes of ketoacidosis that can be fatal, and alternative long-term strategies such as islet cell transplantation or implantation of insulin infusion pumps are currently under active investigation. The liver is a key organ in maintaining glucose homeostasis in response to insulin and in ketogenesis during severe insulin deficiency. An adjuvant treatment for IDDM is hepatic insulin gene expression, whereby insulin is produced following transfer of the insulin gene into parenchymal cells of the liver. We have previously shown that the administration of a recombinant retroviral vector expressing the rat preproinsulin-1 cDNA to streptozotocin-induced diabetic rats can completely prevent ketoacidosis and normalize their fasting blood glucose levels. Further experiments performed with a recombinant retroviral vector expressing a form of the rat preproinsulin-1 cDNA engineered to allow its processing to mature insulin in hepatocytes have defined the therapeutic window that will prevent ketoacidosis without significant risk of hypoglycemia secondary to hyperinsulinemia. The objectives of the current proposal are: 1) To obtain similar therapeutic results using non-invasive alternatives to the surgical partial hepatectomy that was necessary to achieve significant retrovirus-mediated transduction of hepatocytes in the previous studies; 2) To achieve some form of regulated insulin expression, so that insulin expression is induced under conditions of hyperglycemia and suppressed under conditions of hyperinsulinemia. Such regulation is not intended to restore the rapid physiological control of insulin secretion that normally occurs in response to changes in blood glucose levels, but rather to serve as a safeguard against prolonged periods of hyper- or hypoglycemia. Finally, using the naturally-occurring BB Worcester rat model of diabetes, the hypothesis that a recombinant retroviral vector incorporating these features of insulin expression and regulation can be used to prevent both the acute and chronic complications of IDDM will be rigorously tested. Successful conduct of the proposed research will lead to the development of a novel modality for adjuvant treatment of IDDM in humans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: HINDBRAIN MECHANISMS OF HYPOGLYCEMIA UNAWARNESS Principal Investigator & Institution: Ritter, S W.; Professor; Vet & Comp Anat/Pharm/Physiol; Washington State University 423 Neill Hall Pullman, Wa 99164 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-JUL-2006 Summary: (provided by applicant): The overall aim of this project is to understand the mechanisms underlying Hypoglycemia-Associated Autonomic Failure (HAAF), a lifethreatening clinical syndrome of reduced behavioral, autonomic and neuroendocrine responsiveness to hypoglycemia resulting from prior hypoglycemic bouts. Compelling evidence indicates that glucocorticoids are involved in the pathogenesis of HAAF, because they are dramatically elevated by glucoprivation and because administration of exogenous glucocorticoids can reproduce the symptoms of HAAF. This proposal will focus on hindbrain mechanisms involved in HAAF. Hindbrain glucoreceptors control
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two important glucoregulatory responses, increased food intake and adrenal medullary secretion. The first specific aim is to determine whether hindbrain glucoreceptors also mediate the glucoprivic control of glucocorticoid secretion. The second specific aim focuses on hindbrain NE/E neurons. These neurons are crucial for feeding, adrenal medullary and corticosterone responses to glucoprivation and impairment in their function results in symptoms similar to HAAF. This proposal will investigate the multiple pathways through which their control of corticosterone secretion may be mediated. The third specific aim will investigate the importance of NE/E neurons as a site for corticosterone feedback effects that could result in suppression of their activity during HAAF. Many of these neurons possess glucocorticoid receptors. The proposed work will attempt to relate the presence of glucocorticoid receptors on specific populations of NE/E neurons with their functions and involvement in HAAF. The last specific aim is to identify the parameters of glucocorticoid elevation that result in HAAF with particular focus on the magnitude and duration of the secretory event. Corticosterone infusions and specific stressors with differing effects on corticosterone secretion will be examined for their ability to induce HAAF. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HORMONAL REGULATION OF GLYCOGEN SYNTHESIS Principal Investigator & Institution: Saltiel, Alan R.; Professor of Medicine and Physiology; Internal Medicine; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002; Project Start 15-FEB-2002; Project End 31-JAN-2007 Summary: There is little doubt that we are in the midst of a worldwide epidemic of diabetes. Almost 16 million people in the US are thought to be afflicted, a third of whom are undiagnosed. Insulin resistance is recognized as a characteristic trait of the disease, defined by the inability to respond to normal circulating levels of insulin. The primary lesion in this state involves defects in the uptake and storage of glucose in muscle and fat cells. Targeting these defects holds the key to the development of new therapeutic approaches. However, understanding the specific lesions that cause insulin resistance in patients with type 2 diabetes will first require a better grasp of the cell biology of insulin action. To this end, the molecular events involved in the regulation of glycogen synthesis by insulin will be investigated, with special attention to the role of a newly described scaffolding protein, PTG, in the regulation of protein dephosphorylation. In Aim l, the molecular basis for the existence of multiple scaffolding proteins for protein phosphatase 1 (PP1) will be investigated, evaluating the hypothesis that each member of this family has a defined separate function in signal transduction. The structure/function relationships of these molecules will be analyzed by a series of deletion and chimeric mutants. This will be followed by evaluation of the effects of the mutants on glycogen metabolism in cell models, and in intact rat liver. Aim 2 will focus on dissecting the signaling pathway that mediates the activation of PP1 by insulin at the glycogen pellet, resulting in the stimulation of glycogen synthase. This approach will pursue two novel hypotheses involving the identification of regulatory proteins that might be substrates for phosphorylation. The physiological function of PTG will be investigated in Aim 3, by the targeted disruption of the PTG gene in mice. Together, these approaches will allow for the evaluation of the importance of this pathway in insulin action, setting the stage for future investigations into its potential role in the development of diabetes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: HYPERGLYCEMIA AND ADVERSE PREGNANCY OUTCOMEN Principal Investigator & Institution: Metzger, Boyd Northwestern University 633 Clark St Evanston, Il 60208
E.;
Professor;
Medicine;
Timing: Fiscal Year 2001; 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 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: HYPOGLYCEMIA PREVENTION
&
DRIVING:INCIDENCE,
MECHANISMS,
Principal Investigator & Institution: Cox, Daniel J.; Psychiatric Medicine; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904 Timing: Fiscal Year 2003; Project Start 01-JAN-1982; Project End 31-JAN-2006 Summary: (provided by applicant): Intensive insulin therapy for Type 1 Diabetes Mellitus (T1DM) is associated with an increased risk of hypoglycemia. Our past NIHfunded research, investigating the biopsychobehavioral causes and effects of hypoglycemia, has yielded important and unique, albeit post hoc, findings about hypoglycemia and driving in T1DM. We demonstrated that mild hypoglycemia (e.g., 65 mg/dl) impairs cognitive-motor, judgment and driving performance. Additionally, our
42
Hypoglycemia
11-site retrospective survey of 600 drivers with and 300 drivers without diabetes found that those with T1DM had twice as many auto crashes and violations and experienced hypoglycemic stupor 4 times as often while driving than either T2DM or nondiabetic drivers (p's<.01); Post hoc analyses revealed that T1DM drivers who had crashed/hypoglycemic stupor in the previous 2 years had a lower Blood Glucose (BG) threshold for deciding when not to drive, were less likely to measure BG before driving, were more likely to have mild hypoglycemia while driving, and were less likely to have carbohydrates in the car (p's<.03). Finally, our previous research demonstrates that judgment about driving when BG is low can be improved, and number of moving vehicle violations and crashes can be reduced, through psycho-behavioral interventions. Based on these findings, we propose the first, a priori, prospective, multi-center investigation of hypoglycemia and driving in T1DM drivers who are thought to be at High vs. Low risk for driving mishaps. This study has three phases: Phase 1 will involve recruiting 275 High and 275 Low risk T1DM drivers, from three diverse sites in the U.S., and prospectively tracking diabetes self-management behaviors and driving mishaps over a 12-month period. Phase 2 will be intensive and experimental UVA field and hospital-based studies investigating the physiological, behavioral and psychological parameters of driving and self-regulation during euglycemia and hypoglycemia. Phase 3 will include the pilot testing of an intervention aimed at preventing hypoglycemiarelated driving mishaps. The proposed research is designed to: A) document the frequency of hypoglycemia-related driving mishaps, e.g., driving errors that may or may not result in a crash or citation; B) determine mechanisms underlying these mishaps, testing a diabetes-specific causal model we have developed; and C) create a database on which to begin to develop an intervention program intended to reduce the factors associated with hypoglycemia-related driving mishaps; and, D) pilot test an intervention designed to reduce risk of driving mishaps due to hypoglycemia. Ultimately, this research may enhance driving safety for people with T1DM. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HYPOGLYCEMIA & EXERCISE IN CHILDREN WITH TYPE 1 DIABETES Principal Investigator & Institution: Galassetti, Pietro; Pediatrics; University of California Irvine Irvine, Ca 926977600 Timing: Fiscal Year 2003; Project Start 25-SEP-2003; Project End 31-JUL-2008 Summary: (provided by applicant): Clinical research has long been a central component in the career of the candidate. UCI's strong interest in developing metabolic research and its solid history of exercise and pediatric research, well match the candidate's research interest and offers a unique potential for career development. The candidate's long-term plan is to establish an independent line of studies focused on altered mechanisms of stress responses; gradually become an independently funded investigator; and eventually coordinate, alongside his own research, a broad -range of metabolic clinical studies by UCI investigators with a variety of research interests. Initial studies, proposed in this application, are designed to identify novel physiological mechanisms causing the alarmingly high incidence of hypoglycemia in children with Type 1 diabetes. High levels of spontaneous physical activity in these children induce rapidly changing patterns of metabolic demand, contribute to glucose instability, and often result in exercise-associated hypoglycemia. Exercise is important in diabetic children, preventing cardiovascular disease, improving glycemic control/insulin sensitivity, and exerting beneficial effects on development and growth. We hypothesize that the neuroendocrine and metabolic responses which prevent hypoglycemia during
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exercise in the healthy child, acutely fail in the diabetic. In adult patients, exercise responses are acutely reduced by antecedent stress; it is unknown whether this also occurs in children, who are metabolically very different from adults. In addition, based on the new observation made in the candidate's mentor's laboratory that in healthy children exercise acutely increases levels of inflammatory cytokines and growth factors, we will test the novel hypothesis that in diabetic children altered secretion of these mediators may contribute to glucose instability. IL-6, the most abundantly secreted cytokine during exercise, is most likely to impact glucose homeostasis due to recently discovered yet still unclear glucoregulatory properties. This comprehensive approach will be used to define whether adaptive responses to exercise are altered in diabetic children, as compared to controls, and if alterations correlate with gender and/or physical fitness. We will also investigate how the presence and characteristics of antecedent hypoglycemia, with emphasis on nocturnal hypoglycemia, affect children's adaptive response to exercise. Techniques will include maximal/intermittent exercise testing, euglycemic glucose clamping, indirect calorimetry, continuous glucose monitoring, stable isotope glucose and lipid turnover assessment, and hormonal, cytokine, and intermediate metabolite analysis. The results from our studies will hopefully provide the conceptual basis for new therapeutic strategies aimed at correcting the high incidence of hypoglycemia in children with diabetes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FUNCTION
HYPOGLYCEMIA
AND
AUTONOMIC
NERVOUS
SYSTEM
Principal Investigator & Institution: Freeman, Roy; Associate Professor of Neurology; Beth Israel Deaconess Medical Center St 1005 Boston, Ma 02215 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-JUL-2008 Summary: The Diabetes Control and Complications Trial and the United Kingdom Prospective Diabetes Study have documented unequivocally that improved glycemic control decreases the incidence and progression of microvascular complicatons of diabetes. The implementation of regimens to rigorously control blood sugar in diabetic patients has led to an increased incidence of severe iatrogenic hypoglycemic events that have limited glycemic management of diabetes mellitus. Recent antecedent iatrogenic hypoglycemia impairs the neuroende:rine and autonomic response to subsequent hypoglycemia - a disorder known as hypoglycemia associated autonomic failure - thus increasing the predisposition to severe hypoglycemia. It is not known whether antecedent hypoglycemia has more general effects on autonomic nervous system function. Impaired autonomic function is associated with increased mortality and morbidity in individuals with diabetes mellitus. If hypoglycemia induces generalized autonomic dysfunction it may further increase the mortality and morbidity associated with diabetes mellitus. The goal of this research is to understand the mechanisms of hypoglycemia associated autonomic failure. The proposed studies test the hypothesis that antecedent hypoglycemia not only impairs the counterregulatory response to subsequent hypoglycemia but also impairs cardiovascular autonomic function in nonhypoglycemic individuals. These studies will examine those markers of cardiovascular autonomic function that, when impaired, are associated with increased morbidity and mortality in patients with diabetes. Furthermore, we hypothesize that antecedent hypoglycemia causes a rise in serum cortisol and that cortisol activation of glucocorticoid receptors mediates the development of hypoglycemia associated autonomic failure. The specific aims for the proposal are to assess autonomic control of cardiovascular function following antecedent euglycemia and hypoglycemia. In
44
Hypoglycemia
addition, we will determine whether administration of a glucocorticoid receptor antagonist, mifepristone, prior to antecedent hypoglycemia improves the autonomic and neuroendocrine response to subsequent hypoglycemia in healthy men and women. Thus, the broad long term objectives of the proposal are to fully understand the mechanisms and consequences of hypoglycemia associated autonomic failure with the ultimate goal of finding an efficacious treatment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HYPOGLYCEMIA AUTONOMIC DYSFUNCTION
AND
EXERCISE
ASSOCIATED
WITH
Principal Investigator & Institution: Davis, Stephen N.; Professor of Medicine; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2007 Summary: (provided by applicant): Good glycemic control reduces the onset and slows the progression of microvascular complications in Type 1 and Type 2 diabetic patients (DM). Unfortunately, preventing the goal of euglycemia in diabetic patients is the associated three-fold increase in severe hypoglycemia. During the last decade, studies have determined that acquired autonomic nervous system (ANS) failure is implicated in the pathogenesis of hypoglycemia occurring in intensively treated DM. Central to the development of acquired ANS failure is the occurrence of prior episodes of hypoglycemia. Previous work from my own and other laboratories have demonstrated that increases in plasma cortisol can result in acute ANS failure during subsequent stress. These results allow the formulation of a plausible hypothesis stating that an increase in plasma cortisol is a significant mechanism responsible for hypoglycemiaassociated autonomic failure. Type 1 diabetic and healthy women have significantly reduced ANS responses during hypoglycemia and exercise. The mechanisms responsible for this large sexual dimorphism is unknown. We hypothesize that estrogen, another steroid hormone, regulates ANS responses and is the major mechanism responsible for this finding. Acquired ANS failure can also occur during exercise. The mechanisms regulating the development of exercise related autonomic failure are unknown, but need to be determined. The studies outlined in this proposal are therefore focused at determining the in-vivo mechanisms regulating ANS counterregulatory failure during hypoglycemia and exercise in healthy and diabetic humans. Studies will be proposed to determine whether antecedent hypoglycemia reduces the metabolic and cardiovascular effects of the critical hormone epinephrine. This information is needed as treatment strategies simply aimed at increasing ANS ressponses during physiologic stress in diabetics will have limited effectiveness if target organs are unresponsive. Experiments will use the glucose clamp technique. ANS responses to hypoglycemia and exercise will be assessed by measuring circulating catecholamines, pancreatic polypeptide, muscle sympathetic nerve activity (MSNA), and heart rate variability. Metabolic counterregulatory mechanisms will be determined by measuring glucose and glycerol turnover, substrate levels, and substrate oxidation via indirect calorimetry. The specific aims of this proposal are to determine: 1) the mechanisms responsible for cortisol inducing poglycemia-associatedautonomic dysfunction in normnal man and type 1 diabetes, 2) the effects of prior hypoglycemia on subsequent metabolic/cardiovascular responses to epinephrine in healthy and type 2 diabetic man, 3) if dihydroepiandrostenedione can prevent hypoglycemia associated-autonomic dysfunction, and 4) the mechanism responsible for the sexual dimorphism present in ANS counterregulatory responses to hypoglycemia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: HYPOGLYCEMIA AND THE DEVELOPING BRAIN Principal Investigator & Institution: Vannucci, Susan J.; Professor; Pediatrics; Columbia University Health Sciences New York, Ny 10032 Timing: Fiscal Year 2003; Project Start 01-FEB-2003; Project End 31-JAN-2006 Summary: (provided by applicant): The overall goal of this research proposal is to determine the short- and long-term effects of recurrent hypoglycemia on the developing brain. Hypoglycemia is a common metabolic abnormality in infants, which can result from a number of clinical conditions producing imbalances in glucose supply and utilization that are recurrent or persistent. In addition, young children with insulindependent diabetes mellitus (IDDM) suffer repeated episodes of hypoglycemia and resultant neuroglycopenia. The effects of recurrent or persistent periods of hypoglycemia on the developing brain are unknown. We have developed a model of recurrent insulin-induced hypoglycemia in the immature rat, consisting of two episodes/day for 2 weeks from postnatal day 12 to 26 (P12-P26). Our preliminary data demonstrate that this insult produces cell damage and reactive gliosis in hippocampus, cortex, and hypothalamus of immature rats, apparent at P16 and maintained at P35, following return to normoglycemia. To further investigate the identity of the vulnerable cells, as well as the impact on functional outcome and potential therapeutic intervention/prevention, this exploratory proposal will pursue 4 Specific Aims: 1) To determine the time-course and cell specify of hypoglycemia-induced cell death in the developing rat brain. The hypothesis to be tested is that the damaged cells are neurons in vulnerable regions of hippocampus, cortex, and hypothalamus- specifically the glucose-sensitive neurons of the ventromedial hypothalamus and the arcuate nucleus; 2) to determine the mechanism(s) of hypoglycemia-induced cell death during development and the role of the apoptosome. The hypothesis to be tested is that both enhanced sensitivity to glutamate excitotoxicity and increased caspase 3 activity promote increased sensitivity to hypoglycemia in vulnerable neurons; 3) To determine the shortand long term functional outcome of hypoglycemia-induced cell death through behavioral tests that represent the initiation of a core program for behavioral testing over the lifespan. The hypothesis to be tested is that hypoglycemia-induced neuronal damage will adversely alter both hippocampal and hypothalamic function and that these modalities will be able to be evaluated over the course of the animal's life; and 4) To determine the potential for protection or reversibility of hypoglycemia-induced cell death by anti-apoptotic and anti-excitotoxic strategies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: HYPOGLYCEMIC SIGNALING TARGETS IN ASTROCYTES Principal Investigator & Institution: Mandell, James W.; Pathology; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-JUL-2004 Summary: (provided by applicant): Hypoglycemia is a common complication in the management of diabetes. Severe hypoglycemia can cause seizures, unconsciousness, and irreversible cognitive impairment, presumably because of neuronal injury and death. Astrocytes, the star-shaped glial cells found throughout the brain, perform important roles to support and protect neurons. Recent work indicates that in hypoglycemia, astrocytes are capable of rapidly generating substrates to feed energydepleted neurons, probably by breakdown of intracellular glycogen. The mechanisms by which astrocytes sense dropping glucose levels, and the downstream signaling pathways controlling glycogen metabolism, are poorly understood. We propose a
46
Hypoglycemia
discovery-based, but focused approach to identify components of astrocytic hypoglycemic signaling pathways, utilizing two powerful and complementary methodologies: proteomics and a novel method of expression cloning. We will test a general hypothesis: Astrocytes possess specialized glucose signaling molecules and mechanisms enabling rapid regulation of substrates for neuronal metabolism in hypoglycemia. The specific aims of the project are: 1) Identify molecular targets of acute, subacute and episodic hypoglycemia in astrocytes using two independent and complementary approaches: a) proteomics (two-dimensional gel electrophoresis with protein identification by mass spectrometry); and b) FIMS, a novel expression cloning method developed in our laboratory. 2) Validate targets using cell culture and in vivo models of hypoglycemia. The entire set of identified hypoglycemia-regulated proteins will be made available as a database for the research community. A subset of the targets identified will be the subject of future hypothesis-driven research projects in our laboratory. The longterm goal is to develop pharmacologic or molecular methods to augment or modulate neuroprotective aspects of the astrocytic response to hypoglycemia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HYPOXIC/AGLYCEMIC STRESS TO ENDOTHELIAL CELLS OF THE BLO Principal Investigator & Institution: Davis, Thomas P.; Professor; Pharmacology; University of Arizona P O Box 3308 Tucson, Az 857223308 Timing: Fiscal Year 2001; Project Start 01-JAN-2000; Project End 31-DEC-2004 Summary: Understanding BBB stroke pathophysiology is critical since stroke is a leading cause of death and disability and increased cerebrovascular permeability is an important factor for the development of ischemic brain damage and edema formation. Vasogenic brain edema, due to a BBB opening is the type of edema that is present in the brain after injury induced by a cerebrovascular accident. Vasogenic brain edema can result from opening of tight junctions at the BBB or an increase in pinocytotic activity. Damage to the BBB from ischemia/stroke can result in poor clinical outcomes during stroke recovery, such as vasogenic brain edema and inflammation. In addition, changes in BB transport characteristics may influence the transport of clinically useful medications used to either treat the ischemic episode or medicate other disease stages. Our major hypothesis is that hypoxia/aglycemia and reperfusion (associated with stroke) alters both the expression of BB specific proteins and the permeability and transport of critical solutes across the BBB, thereby contributing to the development and severity of stroke. To investigate this hypothesis, our major objective and specific aims are to investigate and quantify the effect of hypoxia/aglycemia/reoxygenation on the endothelial cells of the BBB by quantifying effects on cell resistance, permeability, tight junctional protein/cytoskeletal protein expression and transcriptional/posttranscriptional expression of specific proteins associated with hypoxia. We will also identify the role in calcium in hypoxia/aglycemia/reoxygenation and determine the role of astrocytes. The techniques we will use are both in vitro and in situ coupling our experience of analytical biochemistry and vascular biology in a focused program to study the effect of hypoxic/aglycemic stress on endothelial cells of the BBB. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: INSULIN PRODUCING VECTORS FOR GENE THERAPY OF DIABETES Principal Investigator & Institution: Ripps, Michael E.; Laboratory Medicine; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2001; Project Start 15-FEB-1999; Project End 31-DEC-2003 Summary: Strong impetus exists for developing improved modes of insulin delivery for the treatment of diabetes mellitus. The insertion of appropriately regulated insulin genes into non-islet tissues is a potential strategy for the treatment of type I diabetes, in which islet cells are destroyed by autoimmune mechanism. The objective of the proposed project is to explore an approach to gene therapy for diabetes for engineering glucose regulated insulin production in extra-pancreatic sites. Our approach will be to target insulin expression to hepatocytes and intestinal epithelial cells in vivo using an insulin gene construct driven by the liver-type pyruvate kinase (L-PK) promoter. Since L-PK promoter activity is stimulated by glucose and blocked by glucagon and cyclic AMP, we expect that insulin synthesis and secretion will increase after a carbohydrate meal, and that possible over-production of insulin leading to severe hypoglycemia may be prevented by the cAMP-mediated actions of glucagon and epinephrine. Since the L-PK promoter requires permissive amounts of insulin to be active, a second gene construct expressing insulin from a modified metallothionein promoter will be transferred along with the L-PK/insulin gene to provide a basal level of insulin. Double gene cassettes will be packaged into adeno-associated virus vectors and transferred in vivo to mice rendered diabetic by ablation of pancreatic beta cells using the drug streptozotocin. The time course of L-PK/insulin gene activation and repression will be determine after glucose loads and during insulin-induced hypoglycemia. Possible amelioration of the diabetic state will be assessed by oral glucose tolerance tests and measurement of glycohemoglobin levels. New initiatives in gene therapy will undoubtedly require the development of control systems to achieve the desired expression level for varying physiological or therapeutic circumstances. This project will assess a new therapeutic approach to diabetes and may also serve as a model for future attempts to engineer control systems for gene transfer. Furthermore, the Research Center Award will enhance my development as a physician-scientist and allow me to reach my long-term goal of an independent research career in academic medicine. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ION CHANNEL MODULATION IN CEREBRAL ISCHEMIA Principal Investigator & Institution: Elliott, John P.; Healthone Alliance 899 Logan St, Ste 203 Denver, Co 80203 Timing: Fiscal Year 2003; Project Start 01-JAN-2003; Project End 31-DEC-2007 Summary: (provided by applicant): Stroke is the third largest cause of death and the leading cause of disability in the United States. The majority of strokes (80%) are ischemic and to date there has been limited therapeutic success in part because of single target treatment strategies ignoring the complex molecular and cellular events occurring after ischemia. Recent technological advances have allowed the analysis of large molecular expression databases and the consideration of novel parallel and time-specific therapeutic approaches in complex biologic systems. The Candidate is a neurosurgeon specializing in neurovascular and neuro-critical care, who proposes a career development plan as a clinician investigator with focused mentorship in molecular neurobiology, genomics, proteomics and bioinformatics. He proposes to study the molecular modulationof ion channels in the hours to days following hypoxia-
48
Hypoglycemia
hypoglycemia (HH) in relation to hippocampal neuronal cell death and also in association with the adaptive response known as ischemic tolerance. He has generated preliminary data demonstrating differential genomic expression of the Galanin receptor and proteomic expression of hippocalcin, both G-protein-linked receptors, and other potential sodium channel modulators in mouse hippocampal cultures exposed to HH. Sodium channel blockade is known to be neuroprotective and G-Protein receptor activation is known to result in sustained neuronal sodium currents, which may be associated with increased cell death. The proposed research will address the following hypotheses: Aim 1: There is a time-specific differential RNA and protein expression of ion channel modulators in the first 48 hours following ischemia; this is predicted to be critically distinct from expression changes following an initial conditioning exposure to sublethal HH, i.e. induction of ischemic tolerance. Aim 2: Ion channel modulators identified in Aim 1 can be experimentally manipulated to decrease hippocampal neuronal cell death by multiple mechanisms including the decrease of persistent sodium currents. The Candidate shall benefit from the coordinated mentorship of several leading investigators in a structured programmatic environment including core facilities for the proposed investigations. Results from this research will uncover new strategies for brain protection and ischemic therapy aimed at targeting of novel molecular pathways differentially involved in ischemic cell death and ischemic tolerance. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IONOTROPIC NMDA RECEPTOR ANTAQONISTS Principal Investigator & Institution: Adejare, Adeboye; Associate Pharmaceutical Science; Idaho State University Pocatello, Id 83201
Professor;
Timing: Fiscal Year 2002; Project Start 01-JUN-1998; Project End 31-JAN-2004 Summary: (provided by applicant): This project deals with the design, syntheses, pharmacological evaluations, and computational studies of non-competitive antagonists on N-methyl-D-aspartate (NMDA) receptors. These transmembrane amino acid receptors are located on neurons in the central nervous system. Upon excitation of these receptors, a cation channel opens. The target compounds are expected to bind inside of and block this channel, thus preventing further firing of the neuron. Such overfiring occurs during states of ischemia and hypoglycemia when levels of the endogenous excitants l-glutamate and l-aspartate are elevated. It can result in neuronal degeneration and cell death. This is observed in stroke and is suspected to play roles in neuronal diseases such as Alzheimer's, Parkinson's, and epilepsy. Consequently, several groups are studying NMDA receptors as a therapeutic target. For this study, the lead compound is the dissociative anesthetic phencyclidine (PCP). It is known to bind to NMDA, sigma (s), and cholinergic (nicotinic) receptors, inhibits reuptake of biogenic amines (dopamine, norepinephrine, and epinephrine), and interacts with voltage-gated potassium (K+) channels. Consequently, it exhibits a lot of activities, many of which are undesirable. It also has a high abuse potential. Some structure-activity relationship studies have been conducted on PCP and its analogs. The good news are that several of those compounds have been found to exhibit less neurological toxicities than conventional NMDA antagonists and have made it to clinical trials in humans. The main problem encountered in the trials was psychosis and the compounds were not developed further for this reason. There is some literature linking activity on s receptors with psychosis though this remains controversial. Our hypothesis is that appropriately designed PCP analogs will be selective non-competitive NMDA receptor antagonists, by being more potent on those receptors and/or significantly less on alpha receptors. A corollary to this hypothesis is that a compound that is selective for NMDA receptors and
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which binds poorly on alpha-receptors will not have psychotic effects. The goals of this study are to synthesize three series of compounds designed to probe differences in NMDA and alpha-receptor binding sites. We also seek to continue developing a computational model to decipher any correlation between structures of the target compounds and binding affinities on NMDA receptors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: K EXCITOTOXICITY
+
EFFLUX--ROLE
IN
CA++
HOMEOSTASIS
AND
Principal Investigator & Institution: Kiedrowski, Lech; Psychiatry; University of Illinois at Chicago 1737 West Polk Street Chicago, Il 60612 Timing: Fiscal Year 2001; Project Start 01-JAN-1999; Project End 31-DEC-2003 Summary: Within only 2-3 min of brain ischemia, extracellular K+ concentrations ([K+])o reach 60 - 80 mM, which implies that the excitotoxic action of glutamate during ischemia is executed at highly elevated [K+]o. The proposed research will study whether such high [K+]o affects mechanisms of glutamate excitotoxicity. The hypothesis "High [K+]o reduces the electrochemical Ca2+ driving force (ECDF) in neurons exposed to glutamate receptor agonists" will be tested in Aim 1: "Study the effects of various [K+]o on the plasma membrane potential (Em) and the cytoplasmic Ca2+ concentration ([Ca2+]c) in cultured cortical and cerebellar neurons exposed to glutamate receptor agonists". To this end, neurons will be loaded with Em- and Ca2+-sensitive fluorescent probes. This hypothesis, if true, predicts that high [K+]o may prevent excitotoxicity by decreasing the glutamate mediated Ca2+ influx across the plasma membrane. It is also possible, however, that glutamate may collapse the Na+ and K+ concentration gradients across the plasma membrane and, consequently, set Em close to zero regardless of [K+]o. To test whether this is the case, the cytoplasmic Na+ and K+ concentrations will be measured in parallel experiments in neurons loaded with Na+- and K+-sensitive fluorescent probes. An alternative hypothesis, will be tested in Aim 2: "Determine whether increasing [K+]o may inhibit the glutamate-mediated Ca2+ influx in a manner not related to the plasma membrane depolarization". To this end, the effects of [K+]o on Ca2+ accumulation stimulated by glutamate receptor agonists will be studied in neurons depolarized by a Na+ and K+ ionophore, gramicidin. Finally, in Aim 3: "Test whether restoration of low [K+]o following ischemia in vitro causes a delayed Ca2+ accumulation and compromises neuronal survival", it will be studied whether [K+]o during the postischemic period affects Ca2+ homeostasis and is related to improved or compromised neuronal survival during the next 24 hours. These studies may yield a new target for pharmacological intervention to decrease neuronal death following ischemia or hypoglycemia, namely, to prevent excessive K+ loss from the brain during reperfusion. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: LIFESPAN HYPOGLYCEMIA
NEURONAL/GLIAL
METABOLISM
DURING
Principal Investigator & Institution: Turner, Dennis A.; Professor; Surgery; Duke University Durham, Nc 27706 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-JUL-2004 Summary: (provided by applicant): The central hypothesis of this project focuses on protective strategies for enhancing neuronal metabolism during and after short-term hypoglycemia. Several related mechanisms will be studied using physiological and
50
Hypoglycemia
mitochondrial imaging techniques in acute hippocampal slices, following hypoglycemia. In particular, we will directly assess neuronal-glial metabolic interrelationships by analyzing whether the "lactate shuttle" is altered as a function of age. We will also directly measure the presence or absence of mitochondrial permeability transition as a function of age. Because slice metabolism varies as a function of slice oxygenation, age of the tissue and slice conditions (i.e., interface versus submerged slice conditions), direct oxygen tension measurements will be performed in the tissue using a Clark-style oxygen microelectrode at the same depth as the electrical recordings. The oxygen tension monitoring will ensure that metabolic substrate provision is controlled appropriately within the slice. Neuronal-glial metabolic interactions will be analyzed using glial poisoning with fluoroacetate to estimate direct neuronal contribution to glycolysis and aerobic metabolism, by substituting lactate and pyruvate. Pyruvate will be assessed as a potential treatment for preventing hypoglycemic damage. Occurrence and prevention of mitochondrial permeability transition with these stresses will also be assessed, using cyclosporin A and newer analogs such as N-Me-VaI-CSA. Analysis of these mechanisms which lead to enhanced susceptibility to neuronal damage following hypoglycemia are likely to lead to enhanced treatment. Mechanisms of neuronal injury are expected to vary depending on the duration and severity of the hypoglycemia, and the age of the animal from which hippocampal slices were harvested. These in vitro slice models of hypoglycemia will contribute greatly to the understanding of neuronal metabolism, and particularly the metabolic interactions between neurons and glia as a function of lifespan. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: LONG TERM GLUCOSE SENSING & PHYSIOLOGIC INSULIN DELIVERY Principal Investigator & Institution: Steil, Garry M.; Medtronic Minimed 18000 Devonshire St Los Angeles, Ca 91325 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-JUL-2005 Summary: (provided by applicant): Approximately 4 million individuals with Type 1 diabetes are treated with insulin in the U.S. individual with diabetes are constantly challenged to measure their blood glucose and administer the appropriate insulin dose to achieve tight glucose control. Tight glucose control, achievable with intensive insulin therapy, dramatically reduces secondary complication of diabetes, but requires frequent painful blood samples and increases the risk of hypoglycemia. Thus, individuals with the disease have long awaited an automatic closed-loop system that would control their glucose without the need for constant intervention. In the present proposal, two closedloop systems to achieve this goal are developed. Both systems use a long-term fully implantable glucose sensor. One of the systems links the sensor to a fully implantable intraperitoneal insulin pump; the second links the sensor to an external insulin delivery pump. It is anticipated that some patients may require the implantable pump and that others will want to have the option of which pump to use. The systems have a common goal - to emulate, as closely as possible; glucose control achieved in a healthy individual. To achieve this goal, a physiology-insulin-delivery algorithm is proposed that emulates B-cell responses to glucose observed in individuals with normal glucose tolerance. The B-cell response is optimally adjusted to overcome delays associated with intraperitoneal (fully implanted pump) or subcutaneous (external pump) insulin delivery. Digital filters are developed to optimally remove noise in the sensor signal. A method of tuning the system, consistent with the level of glucose tolerance achieved by the B-cell is developed. Performance and safety of each system is evaluated. If successful, the
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systems can be expected to revolutionize the treatment of diabetes by dramatically reducing the burden placed on individuals with type 1 diabetes, and by reducing the costs of treating hypoglycemia and secondary complications. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MANIPULATION IMMUNOTHERAPY
OF
CD40
CD40L
IN
CTL
BASED
Principal Investigator & Institution: Schoenberger, Stephen P.; Assistant Member; La Jolla Institute for Allergy/Immunolgy Allergy and Immunology San Diego, Ca 921211118 Timing: Fiscal Year 2001; Project Start 01-APR-2000; Project End 31-MAR-2005 Summary: (Applicant's Abstract) The successful application of cancer immunotherapy will require a deeper understanding of CD8+ cytotoxic T lymphocyte (CTL) regulation in order to effectively control tumor growth while limiting autoimmune damage. Recent insights into the pathways of CTL activation and tolerance suggests that endogenous or transfected CTL populations can be controlled in vivo at the level of antigen-presenting cell (APC) function through manipulation of CD40-CD40L interactions. Towards this, there is clearly a need for physiologically relevant animal models of spontaneous cancer that will allow the study of these tumor-immune system interactions and permit a useful evaluation of APC-focused immunotherapeutic strategies. The goal of this research is to develop such a powerful new model system in which the capacity of APC to regulate tumor-specific CD8+ cytotoxic and CD4+ helper T cell responses can be assessed during the development of a primary endogenous tumor expressing a model self-antigen. Part of this tumor model involves transgenic mice expressing the potent SV40 T antigen oncogene under the control of the rat insulin promoter (RIP-Tag2). RIPTag2 mice develop pancreatic beta-cell tumors leading to autonomous insulin secretion and lethal hypoglycemia within 3-4 months. RIP-Tag2 mice will be crossed with RIPmOVA mice that express ovalbumin (OVA) as a self-antigen in beta cells of the pancreas and proximal tubular cells of the kidney. In RIP-mOVA mice, OVA is efficiently crosspresented on host APC, leading to the deletion of OVA-specific CTL which can be blocked by CD4+ OVA-specific helper T cells. Transgenic OVA-specific CTL (OT-I cells) will be adoptively transferred to the RIP(Tag2 x mOVA) mice at various times during the development of OVA-expressing beta cell tumors. The ability of the CTL to control tumor growth versus causing autoimmune damage will be examined by i) monitoring of blood glucose levels (reflecting tumor burden and autoimmune destruction of normal beta cells), ii) histological examination of pancreas and kidneys, iii) the persistence, and activation/tolerization of transferred CTL (measured in vitro), and iv) effect on survival. APC-focused regulation of the OT-I cells will be attempted using OVA-specific CD4+ T cells or stimulatory anti-CD40 antibodies to induce and maintain OT-I cells and inhibitory anti-CD40L antibodies to tune down the responses of OT-I cells. It is hoped that this project will result in a superior animal model in which to explore factors that influence the balance between tumor control and autoimmunity in CTL-based immunotherapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MECHANISMS OF NEURONAL HYPOGLYCEMIC INJURY Principal Investigator & Institution: Salton, Stephen R.; Fishberg Res Ctr in Neurobiol; Mount Sinai School of Medicine of Nyu of New York University New York, Ny 10029 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-JUL-2006
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Hypoglycemia
Summary: (provided by applicant): Tight control of serum glucose levels is critically important in reducing long-term complications of diabetes mellitus. Accumulating evidence suggests that these long-term benefits are not risk-free, and that recurrent episodes of hypoglycemia, or severe hypoglycemic coma secondary to incorrect insulin dosing, have significant morbidity. Damage to the hippocampus and cerebral cortex has been noted, as have cognitive defects in humans and in animal models. However, the mechanisms that underlie hypoglycemic damage to the nervous system, particularly during embryogenesis, remain largely unknown. We propose to better define how neurons are damaged by hypoglycemia in the nervous system, whether synaptic connectivity and neuronal development are affected, and whether hypoglycemia triggers expression of particular genes within the brain, providing insight into the type of damage that is sustained and identifying possible avenues of therapeutic intervention. Using two complementary hippocampal primary culture models, we plan to identify the pathways that lead to neuronal injury in response to hypoglycemia (Specific Aim I). Neuronal vulnerability to cell death will be determined; type of cell death, death pathways and active intermediates, and the transmitter phenotypes of the affected hippocampal neurons will be defined. In addition, effects of hypoglycemia to delay or disrupt neuronal polarization, axonal and dendritic outgrowth, selective axonal and dendritic protein transport, and synaptogenesis will be analyzed. Since recurrent bouts of hypoglycemia in utero are associated with postnatal cognitive impairment, we propose to examine whether cell death pathways are activated in the hippocampus through exposure to hypoglycemia in utero (Aim II). In addition, we propose to identify genes that are regulated in the embryonic and early post-natal hippocampus by hypoglycemia, which we hope will offer insight into the mechanism(s) by which the hippocampus is damaged. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MEMBRANE TRAFFICKING AND CHANNEL ABUNDANCE Principal Investigator & Institution: Jan, Lily Y.; Professor and Hhmi Investigator; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 94122 Timing: Fiscal Year 2001; Project Start 15-AUG-2001; Project End 31-JUL-2006 Summary: (Provided by Applicant): For signaling to proceed normally in the nervous system, there has to be the right number of the right type of ion channels and transmitter receptors on the neuronal membrane. What kind of quality control machinery can ensure the proper assembly of these membrane protein complexes? How does a cell control the number of channels and receptors on its cell membrane? We have found a novel quality control mechanism that curtails the trafficking of inadequately assembled membrane protein complexes from the endoplasmic reticulum (ER) to the cell membrane. This ensures surface expression of fully assembled ATP-sensitive potassium (K-ATP channels with four Kir6.2 and four SUR subunits, and of properly assembled, heterodimeric GABA-B receptors that can functionally couple to the G protein-activated inwardly rectifying potassium (GIRK or Kir3) channels. The ER retention/retrieval signals in the K-ATP channels also limit the number of these channels on the cell surface. How general might be the use of ER retention/retrieval in the quality control of membrane protein complexes? Does the cell regulate other steps of membrane trafficking to control the number and type of ion channels and transmitter receptors? We have developed new methods to test the hypothesis that the numbers of different potassium channels are subjected to different membrane trafficking regulations. The examples to be used in our study are potassium channels that mediate slow synaptic potentials, control neuronal excitability, and potentially protect central
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neurons under stress. Mutations of potassium channel proteins are known to cause ataxia, epilepsy, deafness, arrhythmia, hypertension, and unchecked insulin release leading to hypoglycemia. Indeed, human epilepsy could result from mutations that reduce the M-type potassium channel activity by only 25 percent. And some of the disease-causing mutations alter the amount of functional potassium channels on the cell membrane. Our goal is to achieve better understanding as to how membrane trafficking regulates channel number and type. This may help us appreciate in the long run how regulation of membrane trafficking might contribute to synaptic plasticity, and whether malfunctions of this process contribute to mental and neurological diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MEMORY AND LEARNING IN CHILDREN WITH IDDM Principal Investigator & Institution: Holmes, Clarissa S.; Professor; Psychology; Virginia Commonwealth University Richmond, Va 232980568 Timing: Fiscal Year 2001; Project Start 15-AUG-2000; Project End 31-JUL-2004 Summary: (adapted from investigator's abstract): The project's long-term goal is the longitudinal study of memory and learning skills in children with insulin-dependent diabetes --- mellitus (IDDM). As children progress through school, information acquisition becomes increasingly visual at the same time that adolescents with diabetes begin to experience central visual processing anomalies. Visual memory and learning is virtually unstudied in youth with diabetes even though difficulties with verbally based acquisition skills have been documented. Problems remembering or learning to accurately implement the diabetes treatment regimen can affect metabolic control and compromise both further cognitive functioning and long-term health status. This application proposes to ascertain the functional impact of memory and learning skills on daily self care behaviors of children. A group of adolescents, ages 12-15, will be followed longitudinally as they enter a crucial developmental transition from parental management of their diabetes to increasing self-care responsibility. Approximately 120 adolescents from Children's National Medical Center in Washington, D.C. will be evaluated initially to provide baseline documentation of their memory and learning skills, their academic achievements as well as their diabetes self-care behaviors. Children will be evaluated every year for a total of 4 assessments over the course of 4 years. An accelerated longitudinal design with growth curve analyses will be used to evaluate the achievement and self-care outcomes related to memory and learning skills. It is hypothesized that visual memory will decrease over time in a linear fashion because the visual system is particularly vulnerable with longer disease duration, even though acuity remains intact. It is hypothesized that verbal memory should remain relatively unchanged over time except for adolescents who experience episodes of severe hypoglycemia, which disrupts left hemisphere medial temporal/hippocampal functioning; modality specific learning patterns over time should follow these memory patterns and better memory should relate to better achievement scores and self-care behaviors, independent of the effect of general intelligence. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MITOCHONDRIAL TRYPANOSOMES
PROTEIN
IMPORT
IN
AFRICAN
Principal Investigator & Institution: Chaudhuri, Minu; Microbiology; Meharry Medical College 1005-D B Todd Blvd Nashville, Tn 37208 Timing: Fiscal Year 2001; Project Start 01-JUN-1998; Project End 31-MAY-2003
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Hypoglycemia
Summary: (Adapted from applicant's abstract) Blood borne parasitic disease are major causes of human morbidity and mortality, particularly in the tropical world. African trypanosomes, the protozoa of the Trypanosoma brucei complex, are such parasites that live extracellularly in the blood and tissue fluids of the vertebrate host, utilizing blood glucose as their sole source of energy eventually leading to hypoglycemia and disease syndrome known as African sleeping sickness. Mitochondrial biogenesis is an essential part of the digenetic life cycle of this protozoa. These cells suppress their mitochondrial activities when they live in the bloodstream of its mammalian host. During bloodmeal, parasites are transferred to the insect gut and there they regenerate their mitochondrial activities. Import of a vast majority of nuclear encoded mitochondrial protein is a necessary process for mitochondrial biogenesis. The goal of this study is to characterize mitochondrial protein import mechanisms in African trypanosomes so as to understand their roles in mitochondrial biogenesis. The initial requirement to accomplish this goal is the isolation and characterization of the trypanosome proteins involved in mitochondrial protein import. The specific aims of this proposal are: 1) to identify and characterize the receptors that import proteins across the outer mitochondrial membrane from T. Brucei; and to assess whether they are differentially expressed during the parasite life cycle; 2) to clone and characterize components of the TOM complex (TOM70, TOM40, TOM22, and TOM20) from T. Brucei; and 3) to study the roles of these cloned proteins in the import of the recombinant trypanosome alternative oxidase protein into isolated mitochondria of T. brucei. Characterization of the mitochondrial import machinery in this parasite may provide insight into genetic control mechanisms in trypanosomes where, in contrast to most eukaryotes, developmental regulation of gene expression is almost entirely post-transcriptional. Understanding of this developmental process will elucidate one of the major aspects of trypanosomal parasitism. This in turn will help us to design rational trypanocidal chemotherapeutic strategies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOLECULAR BASIS OF A NEW FORM OF HYPERINSULINISM Principal Investigator & Institution: Stanley, Charles A.; Chief; Children's Hospital of Philadelphia 34Th St and Civic Ctr Blvd Philadelphia, Pa 19104 Timing: Fiscal Year 2001; Project Start 15-SEP-1998; Project End 31-JUL-2006 Summary: (provided by applicant): Dr. Stanley has recently described a new disorder of hypoglycemia in infants with congenital hyperinsulinism and hyperammonemia (HI/HA syndrome). The principal investigator proposed a few years ago that this disorder is caused by mutations that result in excess activity of glutamate dehydrogenase (GDH). In the first 2 years of this grant, the PI has confirmed that these patients have dominant missense mutations of GDH that impair inhibitory responsiveness to its allosteric effector, GTP. A total of 52 mutations have been identified in GDH, in 3 different domains, which appear to be involved in inhibitory allosteric regulation of the enzyme. The PI has developed a method for expressing human GDH in bacteria to confirm that these mutations can produce defects in allosteric control. The goals of this application are to further define the molecular basis of HI/HA syndrome and to elucidate the consequences of GDH dysregulation on glucose and nitrogen metabolism. There are 3 specific aims: 1) to determine all of the locations of GDH mutations that can cause the HI/HA syndrome and correlate these mutation sites with differences in clinical phenotype; 2) to characterize, by expression of mutant GDH in bacteria, the effects of naturally occurring mutations and of additional designed mutations on enzyme activity and allosteric responsiveness; 3) to define mechanisms by
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which GDH mutations cause abnormal regulation of insulin secretion and ammonia detoxification using transgenic mice expressing mutant enzyme specifically in pancreatic beta-cells or in liver. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOLECULAR GENETIC STUDIES OF GLYCEROL KINASE DEFICIENCY Principal Investigator & Institution: Mccabe, Edward R.; Professor and Chair; Pediatrics; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2001; Project Start 01-AUG-1987; Project End 31-MAY-2004 Summary: (Adapted from investigator's abstract) Glycerol kinase deficiency (GKD) may be caused by deletion of the entire GK gene as part of a contiguous gene syndrome, complex GKD, or by intragenic mutations in isolated GKD. Isolated GKD is associated with two different clinical presentations: the symptomatic form with episodic altered central nervous system status with or without hypoglycemia; or the benign form with incidental observation of pseudohypertriglyceridemia. Using the patients with contiguous gene deletions we cloned two of the genes responsible for the complex phenotype, one of which was GK. It is now proposed to investigate the pathogenesis of GKD by examining the hypothesis that GK mutations will have specific and identifiable effects on GK protein expression and/or function and structure that will alter the concentration and flux of metabolic intermediates involved in glycerolipid and energy metabolism. To pursue this hypothesis the following Specific Aims are proposed: (1) To investigate the effects of GK mutations on GK expression, function and structure we will identify intragenic mutations, determine their effects on expression and function, elucidate their structural consequences, and correlate structure with function in the GK protein; and (2) To understand the pathogenesis of symptomatic GKD, we will investigate the concentration and flux of metabolic intermediates in a knockout mouse model, conditionally rescue or moderate the phenotype to permit survival for metabolic investigations, and introduce wild type and mutant GK genes into the knockout mice by viral mediated gene transfer to study the resulting clinical and biochemical phenotypes. In addition to clarifying the fundamental biology of GK and the pathogenesis of GKD, these investigations will provide basic insights into the dynamics of glycerolipid metabolism and potential tools for studies of tumorigenesis, ethanol oxidation and peroxisomal proliferation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: NEAR-CONTINUOUS GLUCOSE MONITORING IN PEDIATRICS Principal Investigator & Institution: Buckingham, Bruce A.; Pediatrics; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2002; Project Start 30-SEP-2001; Project End 31-AUG-2006 Summary: (prepared by applicant): The investigators propose to develop a systematic approach to evaluating near continuous glucose sensors in children and adolescents. This approach can be used in the assessment of current sensors now available to the public, and for future sensors that become available during this project. Accuracy will be determined using normal controls and children with diabetes. Initial accuracy measurements will be performed in a CRC using a laboratory quality measurement of glucose. The sensors will then be assessed in the home environment to determine their usefulness in detecting changes in blood glucose levels and improving diabetes
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Hypoglycemia
management. The investigators will collect detailed record of food intake, and a continuous record of physical activity will be obtained using an accelerometer as well as psychological assessments. These data will be integrated to evaluate the multiple factors leading to hypoglycemia and variability in blood glucose levels, as well as provide effective tools for improving diabetes management. In the future these data will be valuable in developing algorithms that incorporate this information into a closed loop insulin delivery system. Aim 1 is to determine the accuracy of near-continuous glucose monitors in normal children. This will allow assessment of the possible physiologic effects, such as sleep and physical activity on glucose levels. These studies will also allow determination of the incidence of sensor readings in the hypoglycemic range despite normal blood glucose levels. Aim 2 is to determine the accuracy of nearcontinuous glucose sensors in children with diabetes. Particular attention will be given to the detection of hypoglycemia, especially nocturnal hypoglycemia, and the accuracy of sensors during physical activity. Aim 3 is to assess hypoglycemia in a contemporaneous population of children with Type 1 diabetes using near continuous glucose monitoring. This will be an observational study in a home environment. Aim 4 is to assess the long-term effectiveness of near continuous glucose monitoring on decreasing the frequency and severity of hypoglycemic reactions, and improving glycemic control. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IMAGING
NETWORK
FOR
TRANSLATIONAL
RESEARCH:
OPTICAL
Principal Investigator & Institution: El-Deiry, Wafik S.; Associate Professor; Medicine; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2003; Project Start 26-SEP-2003; Project End 31-AUG-2008 Summary: (provided by applicant): The "Philadelphia Team" of NTROI investigators is asking fundamental questions with respect to cancer development, lymph node metastases, tumor angiogenesis, and understanding therapeutic response and toxicity of chemotherapy. The Team is developing molecular optical imaging techniques and probes to address these fundamental questions in animal models and is employing technology development, optimization of imaging and independent validation using a variety of imaging techniques including optical imaging. The assembled group of investigators is multidisciplinary and multi-institutional, and includes partners from Industry. The focus and motivating force of this Team are the biological questions driving the required molecular imaging techniques, and this represents a major strength of the consortium. The experimental plan is highly translational with specific goals in mind including early detection of colonic neoplasms, early detection of lymphatic spread, non-invasive imaging of angiogenesis and its correlates hypoxia, hypoglycemia and blood flow, and early detection of specific markers of therapeutic response and toxicity. Efforts are in place to develop imaging of metabolic correlates, to make comparisons with other non-invasive methods, and to develop non-invasive optical imaging methods and probes. There is an effort to develop novel therapeutics to treat polyps, to inhibit angiogenesis and to specifically increase tumor apoptosis using available reagents and compounds as well as through high-throughput chemical library screening using specific molecular imaging algorithms to facilitate the identification of novel and effective agents for cancer therapy. Efforts are in place to develop interactions with industry to bring new technologies or models to the consortium, and efforts are in place to identify and fund projects that are in a Developmental phase. The proposed research directions are likely to have significant impact on the national effort in
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translational research to develop better methods for early detection, to better predict therapeutic outcome, and to identify novel therapeutic agents and combinations for the treatment of cancer patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NEUROCOGNITIVE IMPACT OF HYPOGLYCEMIA IN TYPE 1 DIABETES Principal Investigator & Institution: Hershey, Tamara G.; Psychiatry; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-MAY-2008 Summary: (provided by applicant): A common difficulty in managing type 1 diabetes mellitus (T1DM) is hypoglycemia (low blood sugar). This complication is particularly common during childhood. Extreme hypoglycemia can cause coma or death, but less severe hypoglycemia can have consequences for cognitive function. However, it is not well understood how specific these cognitive consequences are and what their neural mechanisms might be, nor how these effects may differ across neural development. We propose to address these important questions. We hypothesize that severe hypoglycemia has a deleterious and specific effect on the hippocampus, a region particularly sensitive to metabolic insults, and on long-term memory, a skill that relies upon the integrity of the hippocampus, in children with T1DM. Using both retrospective and prospective methods, we will determine if the hippocampus is smaller in children with a history of repeated severe hypoglycemia. These measures will be obtained with high resolution structural magnetic resonance imaging and reliable volumetric measurements. We also will determine if reduced hippocampal volumes correlate with reduced long-term memory function. Memory function will be measured in part by a well-validated spatial delayed response measure that we have previously shown to be sensitive to repeated severe hypoglycemia in children with T1DM. We hypothesize that these effects will follow a developmental trajectory, with greater vulnerability in children who experienced hypoglycemia at younger ages due to interruption of critical developmental processes or to increased susceptibility for neuronal impact. The information obtained in this study will be important for the development of optimal treatment regimens for T1DM that minimize cognitive risk and maximize clinical benefit across the lifespan. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: NEURONAL INJURY AND BLOOD GENOMICS Principal Investigator & Institution: Sharp, Frank R.; Professor and Vice-Chairman; Neurology; University of Cincinnati 2624 Clifton Ave Cincinnati, Oh 45221 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2006 Summary: (Adapted from applicant?s abstract): It is hypothesized that the white blood cell genomic response can be used to deduce the presence of neuronal injury due to acute neurological diseases, and that the blood genomic response patterns can be used to differentiate between the diseases causing the neuronal injury. Our preliminary data using microarray technology show unique patterns of gene expression by lymphocytes of adult rats subjected to ischemic strokes, hemorrhagic strokes, status epilepticus, hypoxia, hypoglycemia and sham-surgeries as compared to untouched controls. The first Aim of this proposal will determine whether short durations of global cerebral ischemia, focal cerebral ischemia (transient ischemic attack), hypoglycemia and seizures produce different white blood cell genomic responses in rats that can be used to
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differentiate between these conditions hours to days later. The second Aim will determine whether long durations of global ischemia, hypoglycemia and status epilepticus regulate specific genes in white blood cells in response to the diffuse neuronal injury caused by all of these conditions, and whether these genes can serve as indicators of the diffuse neuronal injury. The genomic expression of neutrophils, lymphocytes and whole blood will be examined at various times after cerebral ischemia, insulin-induced hypoglycemia, seizures and status epilepticus. Genes regulated in the different white blood cells by these conditions will be correlated with the presence of diffuse neuronal cell death in brain using TUNEL staining. The third set of Aims will determine whether the same genes regulated in white blood cells of rodents following single seizures and status epilepticus are also regulated in the white blood cells of men and women patients following seizures and status epilepticus. These studies will also determine whether blood genomic responses can be used to distinguish whether patients have had seizures, pseudoseizures or syncope, and whether some of the neuronal injury-related genes regulated in the blood of rodents with status epilepticus are regulated in patients with status epilepticus. Genes regulated more than two fold on microarrays will be confirmed by quantitative RT-PCR for all of the aims. The goal is to objectively differentiate seizures, syncope, global cerebral ischemia, hypoglycemia, and transient ischemic attacks hours to days after they occur; and to begin to identify blood genomic markers of neuronal death associated with acute neurological diseases that might also be useful in chronic neurological diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NUCLEOSIDE AND NUCLEOTIDE METABOLIZING ENZYMES Principal Investigator & Institution: Mitchell, Beverly S.; Professor; Medicine; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, Nc 27599 Timing: Fiscal Year 2001; Project Start 01-FEB-1983; Project End 31-JAN-2005 Summary: (Applicant's Abstract) The conversion of nucleosides to their corresponding nucleotides is pivotal for both the growth and treatment of tumor cells. It is evident that maintenance of normal levels of endogenous nucleotides is essential to prevent cell cycle arrest and the induction of apoptosis, while the ability of a tumor cell to convert nucleoside analogs to their corresponding triphosphates is essential for a chemotherapeutic response. Steady state levels of nucleotide analogs are achieved and maintained to a large extent by the relative rates of nucleoside phosphorylation by nucleoside kinases and degradation by nucleotidases. Although considerable progress has been made over the past five years in the elucidation of the nucleoside kinases important in drug metabolism and chemotherapeutic sensitivity, far less is known about the nucleotidases and their roles in both normal cellular metabolism and drug resistance. In addition, very little is known about the role of intracellular localization of these enzymes as potential modulators of the interaction and activities. The applicant proposes to address two areas of nucleoside metabolism in tumor cells that will help to elucidate these issues. First, she will characterize the activities of each of the three major 5' nucleotidases that have been identified. She will determine the relationship of ecto-5'nucleotidase expression to multidrug resistance, characterize a new cytosolic nucleotidase (cN-I) with broad specificity that appears very likely to play an important role in drug resistance, and compare its activities to those of the high Km cytosolic nucleotidase (cN-II). In addition, she will determine whether a second isoform of the high Km enzyme exists in human cells, as it does in two other species. As a second new initiative, she will define the role of adenosine kinase in tumor cells and determine whether its association with cytoskeletal elements is important to its function. She will
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also ask whether post-translational modifications or protein-protein interactions of AK are important to its role in regulating cellular adenine nucleotide pools under stress conditions. Finally, she will determine whether deficiency of adenosine kinase and the resulting decrease in adenosine phosphorylation sensitizes cells to the effects of adenine nucleotide depletion under conditions such as hypoxia and glucose deprivation. These studies should extend our knowledge of the metabolism of nucleosides and nucleotides into several new areas and provide the basis for a greater understanding of the mechanisms and consequences of variability in enzyme expression for malignant cells. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PANCREAS AND ISLET TRANSPLANTATION IN HUMANS Principal Investigator & Institution: Robertson, R Paul.; Scientific Director and Ceo; Pacific Northwest Research Institute 720 Broadway Seattle, Wa 98122 Timing: Fiscal Year 2002; Project Start 01-DEC-1988; Project End 31-JUL-2006 Summary: (provided by applicant): The overall objective of these studies is to better understand pancreatic beta and alpha cell function in human recipients of successful pancreas and islet transplantation who are taking immunosuppressive drugs and to better ascertain metabolic consequences of hemi-pancreatectomy in human donors of pancreatic segments. The general intent of the work proposed is to continue our long term follow up of recipients and donors of pancreas transplantation and to initiate new studies of type 1 diabetic recipients of intrahepatic autoislet transplantation with a major emphasis on developing an understanding why initially successful alloislet recipients later develop islet failure; the mechanism of action by which immunosuppressive drugs are toxic to beta cells; and developing a better understanding of the failure of the intrahepatic alpha cell to secrete glucagon during hypoglycemia. The Specific Aims for this proposal are: Specific Aim # 1. To continue long-term, longitudinal studies of insulin secretory reserve and counterregulatory hormonal responses to hypoglycemia in successful recipients of pancreas transplants and in living donors of pancreatic segments to determine whether islet beta cell and alpha cell function are stable or undergo deterioration with time. Specific Aim # 2. To determine whether deterioration in glycemic control after successful alloislet transplantation in type 1 diabetic patients is related to resurgence of autoimmune disease, and/or toxic effects of immunosuppressive drugs, and/or the quantity and quality of islets transplanted and/or the development of obesity and insulin resistance. Specific Aim # 3. To determine, using human isolated islets, the immunosuppressive drug concentrationadverse biologic response relationships for islet hormonal secretion, apoptosis, and cellular replication. Specific Aim #4. To determine whether the glucagon response to hypoglycemia is consistently absent and the epinephrine response to hypoglycemia is consistently restored in successful type 1 diabetic recipients of alloislets. Specific Aim # 5. To determine whether the glucagon response that normally occurs during hypoglycemia is dependent on a decrease in insulin secretion from adjacent beta cells as a "switch off' signal. The metabolic testing of pancreas and islet recipients as well as hemi-pancreatectomized donors will take place at the University of Washington and the University of Minnesota GCRC's. The methods will include glucose potentiation of arginine induced insulin secretion, euglycemic hyperinsulinemic clamps, and hypoglycemic hyperinsulinemic clamps. The laboratory methods will include isolated human islets and studies of insulin promoter activity, insulin mRNA levels, insulin content, and insulin secretion. Studies of the mechanism of glucagon release during hypoglycemia and its disappearance in the absence of beta cells will be conducted in Sprague Dawley rats.
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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: 'PARENT-CHILD CO-REGULATION OF PEDIATRIC DIABETES' Principal Investigator & Institution: Gonder-Frederick, Linda A.; Associate Professor; Psychiatric Medicine; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-JUL-2006 Summary: (provided by applicant): Successful diabetes management relies on a process of self-regulation in which treatment behavior is guided by feedback about changing blood glucose (BG) levels and decision-making. The processes involved in selfregulation have been studied extensively in adults with Type 1 Diabetes Mellitus (T1DM), leading to the development of sophisticated research tools that have significantly advanced our understanding and ability to predict clinical outcome. Additionally, this research has led to the development of a highly effective, empirically based, psychobehavioral intervention, Blood Glucose Awareness Training (BGAT), developed by our research team, that improves self-regulation and clinical outcome in adults with T1DM. Unfortunately, the processes involved in the self-regulation of pediatric diabetes have received virtually no empirical attention. The purpose of the proposed project is to correct this scientific neglect by adapting the conceptual and methodological tools used in adult studies to 1) investigate the process of diabetes regulation by school-aged children (6-11 yrs) with T1DM and their parents and 2) develop and test an intervention to enhance the skills critical to this process. This is an important population to target for this line of inquiry because: 1) children with T1DM and their parents appear to be far less accurate than adult patients in symptom and BG detection; 2) As a group, pediatric patients are more likely to suffer from negative clinical sequelae (e.g., severe hypoglycemia (SH) and DKA); and, 3) Early intervention could have greater public health care benefit by achieving more reductions in acute and long-term complications, health care utilization, and disability. Phases 1A and 1B of the proposed project will provide the first systematic and comprehensive study of symptom recognition, BG detection, decision-making, and subsequent clinical sequelae in schoolaged children with T1DM and their parents. A theoretical model of co-regulation of pediatric diabetes is proposed and tested, in which the behaviors of both parent and child influence the sequence of events that determine avoidance or occurrence of negative outcomes, such as extreme hypo- and hyperglycemia. Based on the findings of these studies and our current BGAT for adults, Phase 1 C will pilot test a translation of this intervention designed for parents of school-aged children with T1DM, BGAT for parents (BGAT-P). This intervention will take advantage of the critical role parents play as the primary teachers of children about diabetes management by including training activities for parents to do with their children designed to improve children's ability to recognize BG symptoms, detect extremes in BG, and make appropriate self-treatment decisions. Based on the findings from this pilot study, and feedback from parents, in Phase 2 BGAT-P will be further refined and tested in a controlled clinical trial to assess its short-term efficacy. Phase 3 is a 12-month follow-up study to determine whether the improvements found in Phase 2 are maintained over time and also to assess the impact of BGAT-P on future clinical negative events, including frequency of SH and DKA experienced by children. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PASSIVATING PROTEINS IN IMPLANTABLE GLUCOSE SENSORS Principal Investigator & Institution: Ward, W K.; Emanuel Hospital and Health Center 2801 N Gantenbein Ave Portland, or 97227 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2005 Summary: (provided by applicant): Inadequate control of blood glucose contributes to the complications of diabetes (renal, retinal, neural). A glucose sensor implanted subcutaneously could provide continuous glucose data, help prevent these complications, and give early warning for hypoglycemia, but the useful life of current devices is limited by foreign body encapsulation. The goal of this work is to develop coatings that will reduce the foreign body reaction to implanted glucose sensors, thereby extending their useful life. Specifically, studies of protein coatings that will reduce monocyte/macrophage adhesion are proposed. The role of fibrinogen and its macrophage-binding region will also be explored. The effect of these coatings will be addressed during chronic studies of glucose sensors implanted subcutaneously in rats. 1. Passivating protein coatings will be created and characterized as follows: a. The degree to which four proteins in buffered solutions will adsorb to polyurethane-coated surfaces will be measured using Iodine-125 radiolabeled proteins. The proteins will include von Willebrand factor, high molecular weight kininogen, albumin, and hemoglobin. Protein concentration will be varied to determine the isotherms for each protein, in order to establish concentrations needed to attain saturation or monolayer adsorption. b. For each protein, the resistance to displacement by blood plasma will be measured. Methods to reduce displacement will be evaluated, including variations in adsorption time and postadsorptive residence time. c. Adsorption conditions found to give coatings that are substantially resistant to displacement will be evaluated in regard to their ability to inhibit macrophage adhesion and foreign body giant cell formation in vitro. d. Glucose sensors preadsorbed with protein under conditions resulting in the least displacement by plasma and the greatest inhibition of monocyte adhesion and foreign body giant cell [FBGC] formation will be sent to Legacy where they will be evaluated to assess useful in vivo lifetime. 2. Passivating antibody coatings will be created and characterized as follows: a. The surface polyurethane will be preadsorbed with flbrinogen and treated with a monoclonal antibody that binds to fibrinogen's macrophage binding region. b. The ability of glutaraldehyde to further stabilize the fibrinogen/antibody-treated surfaces will be assessed. c. The resistance to displacement of the antibody by exposure to plasma will be evaluated. d. The efficacy of antibody blockade to reduce monocyte adhesion and FBGC formation will be evaluated. e. Glucose sensors preadsorbed with fibrinogen and antibody, with or without glutaraldehyde, will be prepared for chronic in vivo evaluation of sensor function. 3. The role of fibrinogen adsorption in the foreign body reaction will be studied as follows: a. A series of gas plasma-deposited polyethylene oxide-like coatings on the sensor will be created under conditions that cause variations in their fibrinogen adsorption. b. The variation of in vitro phagocyte uptake on these surfaces and will be measured. c. Sensor surfaces with high and with low amounts of fibrinogen, including some passivated with antibodies and glutaraldehyde, will be prepared for evaluation in the Legacy animal laboratory. 4. Glucose sensor function will be evaluated after protein adsorption in vitro to assess any coating-induced change. 5. Sensors will be serially evaluated in vivo during normoglycemia and hyperglycemia in order to assess the effect of passivating proteins and antibody-blocked fibrinogen coatings on lag time, sensitivity, stability, and useful sensor life. 6. Because future users with diabetes will wish to minimize capillary blood calibrations, there will be an assessment in coated sensors as to whether calibrations performed only once per week will lead to sufficient sensor accuracy. 7. After explantation, percent of remaining radiolabeled protein will be measured and
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correlated with in vivo function in order to better understand the effects of displacement of passivating proteins or antibody-blocked fibrinogen. 8. A histologic evaluation will be performed to assess the effect of passivating proteins and antibody blocked fibrinogen on the nature of the foreign body capsule. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PLACENTAL GLUCOSE TRANSPORT IN DIABETIC PREGNANCIES Principal Investigator & Institution: Illsley, Nicholas P.; Associate Professor; Ob/Gyn & Women's Health; Univ of Med/Dent Nj Newark Newark, Nj 07103 Timing: Fiscal Year 2001; Project Start 01-AUG-1999; Project End 31-JUL-2003 Summary: Diabetes in pregnancy is associated with a number of perinatal problems such as macrosomia and neonatal hypoglycemia. There is also evidence suggesting that diabetes or even impaired glucose tolerance during pregnancy may be risk factors for the development of diabetes in the offspring. It is clear that the perinatal consequences of gestational diabetes are not simply a function of maternal hyperglycemia, since macrosomic infants are frequently born to mothers whose diabetes is well controlled. Preliminary research suggests that there are increases in the expression and activity of GLUT1 glucose transporters in the syncytial basal membrane of placental tissue from women whose diabetes is adequately controlled. Thus there appear to be continuing perturbations in a system intimately involved in fetal growth and development. It is hypothesized that elevated fetal glucose, resulting from maternal fetal hyperglycemia, causes, through stimulation of fetal growth factors, increased fetoplacental growth including increased expression of the basal membrane GLUT1 glucose transporter, the rate-limiting barrier to placental glucose transport. The resultant increase in transplacental glucose flux prolongs fetal hyperglycemia and leads to continued derangement of the fetal growth axis, despite normalization of maternal plasma glucose. This project is designed to explore this hypothesis by investigating the expression and activity of the human placental GLUT1 glucose transporter in diabetic pregnancies. Aim number 1 : To characterize the changes in placental glucose transporter expression and activity in diabetic pregnancy and to correlate these parameters with measures of maternal glycemic status and fetal growth factors. Aim number 2 : To assess the functional consequences of changes in glucose transporter expression and activity for the placental transfer of glucose. Aim number 3 : To establish the mechanisms responsible for the changes in glucose transporter expression and activity through transcriptional and posttranscriptional modulation and through short term regulatory events. Aim number 4 : To examine the mechanisms governing the (re)distribution of transporters between microvillous and basal membranes. The information obtained from these experimental approaches will significantly advance our understanding of the fetal response to maternal diabetes and the factors generating adverse perinatal consequences. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PROTEOLYSIS IN HYPOGLYCEMIA, IMPACT OF CNS Principal Investigator & Institution: Abumrad, Naji N.; Professor; Sinai Hospital of Baltimore 2401 W Belvedere Ave Baltimore, Md 21215 Timing: Fiscal Year 2001; Project Start 01-JAN-1992; Project End 31-DEC-2002 Summary: Strict glycemic control reduces the occurrence of microvascular complications of diabetes at the cost of a three-fold increase in the frequency of severe hypoglycemia. Euglycemic levels are restored by hormonal and neural counter-regulatory mechanisms
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at the expense of enhance rates of substrate mobilization and rates of glucose production. Our studies have demonstrates that insulin-induced hypoglycemia is also associated with enhanced rates of whole body proteolysis and amino acid oxidation, as well as a significant enhancement in gut protein breakdown. This response, in its majority, is controlled by CNS glucopenia. Our studies suggest that sites responsible for controlling protein and amino acid metabolism during hypoglycemia are most likely located in the hind brain. The general hypothesis of the present proposal is that the "CNS-Gut" axis plays a pivotal role in mobilization of amino acids and proteins during the catabolic response to stress. The studies designed will be performed in the chronically catheterized conscious dog and will investigate the contribution of forebrain and hindbrain neuroglucopenia to triggering the proteolytic responses. In addition, the studies proposed will use surgical and pharmacological interventions to investigate the involvement of direct extrinsic innervation of the "gut" as well as sympathetic, parasympathetic and serotoninergic contribution to modulation the proteolytic responses. The associated hormonal and glucoregulatory responses as well as the contribution of the gut-derived amino acids to enhanced rates of hepatic gluconeogenic amino acid utilization will be assessed using a combination of isotopic and AV difference techniques. Complimentary studies in a rodent model of hypoglycemia to be performed in the final stages of this proposal will be aimed at defining the contribution of specific brain region glucopenia to the proteolytic responses to hypoglycemia. Furthermore, they will determine the specific neurotransmitter alterations that are associated with hypoglycemia. The results from these studies responses to hypoglycemia. These findings will contribute to the understanding of CNS modulation of the peripheral protein and amino acid alterations that are an integral part of the metabolic response to stress. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PSYCHIATRIC DISORDERS IN ADULTS WITH DIABETES MELLITUS Principal Investigator & Institution: Lustman, Patrick J.; Professor of Psychiatry; Psychiatry; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2001; Project Start 01-JUL-1985; Project End 31-MAR-2004 Summary: Diabetes increases the risks of maternal, fetal, and neonatal complications from pregnancy. Tight glycemic control during pregnancy reduces these risks but is difficult to achieve. Major depression is present in approximately 25 percent of diabetic women and is associated with significant deterioration in glycemic control. There has been no study in diabetic or nondiabetic subjects of depression treatment during pregnancy, and the effects of depression treatment on obstetric outcomes remain unknown. Recently, we showed that cognitive behavior therapy (CBT) was an effective nonpharmacologic treatment for depression in diabetes that produced durable improvements in glycemic control. In this study we plan to treat major depression in pregnant diabetic women with CBT and determine its effects on depression, glycemic control, and maternal and neonatal outcomes. We also plan to assess the relationship of diabetes during pregnancy and postpartum depression to neuropsychological development of the infants. 150 pregnant diabetic women will be recruited for study: 100 with and 50 without major depression. The nondepressed subjects function only as a comparison group in some of the statistical analyses. All subjects will be assessed serially during the 2nd and 3rd trimesters and the 1 year postpartum period while receiving the usual degree of intensive medical care for the diabetic pregnancy. Depressed patients will be assigned randomly to treatment with individual CBT (n =50)
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or supportive counseling (n =50). The pregnancy care team is informed of the depression status of all subjects and advised to give usual care for depression. The design blinds the pregnancy care team to treatment assignment, controls for nonspecific effects of attention and the influence of enhanced diabetes control on mood, provides a comparison group likely to remain depression free during gestation and the postpartum period, and is sensitive to human subject issues. We hypothesize that CBT will be superior to supportive counseling in terms of improving depression and glycemic control, and that the treatment-related improvements in glycemic control will reduce the adverse effects of diabetes in pregnancy, including c-section, macrosomia, neonatal hypoglycemia, and fetal hyperinsulinemia. We also expect that by improving glycemic control during pregnancy and reducing the risk of postpartum depression CBT will improve neuropsychological development in the offspring. The findings should demonstrate the relevance of depression treatment to maternal and neonatal outcomes of diabetic pregnancies and translate directly to the management of patients living with diabetes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PTDINS NEURODEGENERATION
TRANSFER
PROTEIN
FUNCTION
AND
Principal Investigator & Institution: Bankaitis, Vytas A.; Professor; Cell and Developmental Biology; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, Nc 27599 Timing: Fiscal Year 2003; Project Start 01-JUN-1998; Project End 31-MAR-2008 Summary: (provided by applicant): The objective of this research is to undertake a detailed analysis of an under-investigated class of proteins: the mammalian phosphatidylinositol/phosphatidylcholine transfer proteins (PITPs). The functions and mechanisms of function of PITPs in mammalian cells remain to be elucidated. The research plan is designed to identify mechanisms of function of a specific mammalian PITP isoform (PITPalpha). This proposal is founded on our creation and characterization of a PITPalpha knockout mouse. PITP-/- mice suffer from spinocerebellar degeneration, hypoglycemia, and failure to absorb dietary fat and fat-soluble vitamins across the small intestine (i.e. a chylomicron retention disease). These phenotypes manifest themselves upon birth and PITPalpha-/- mice rapidly succumb to these disorders. The PITPalpha/- mouse is an ideal disease model in that it is born alive, but manifests powerful phenotypes. The rates of phenotype onset are rapid. Using this unique model, we will undertake three lines of investigation. First, we will restore PITPalpha expression to the small intestine of the PITPalpha-/- mouse to test our hypothesis that the dietary fat malabsorption syndrome is a primary factor in hypoglycemia and spinocerebellar degeneration. In this effort, we propose to develop a cultured enterocyte model in which chylomicron assembly and transport can be studied in detail. Second, our data indicate the PITPalpha-deficient neurons exhibit intrinsic defects; most likely in signaling through the so-called 'survival pathways'. Using genetic, biochemical and signaling approaches we will test this hypothesis in the PITPalpha-/- model. These studies will be complemented by exploitation of a novel Drosophila system for study of PITPct signaling functions. Third, we will use genome engineering approaches to functionally dissect the physiological functions of individual PITPalpha phospholipid transfer activities. In particular, we will test whether the key physiological function of PITPalpha is to facilitate phosphoinositide synthesis and, if so, what specific phosphoinositides are regulated in a PITPalpha-dependent manner and what signaling pathways are involved. PITPs play central roles in regulating signal transduction pathways that interface with
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diverse cellular processes. We now establish that these functional interfaces are relevant to human chylomicron retention disease, disorders of glucose homeostasis, and spinocerebellar degeneration. The Bankaitis laboratory is uniquely poised to address questions of mechanism of PITPalpha function as it has developed unique experimental systems for analysis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REGULATION OF ADRENAL FUNCTION IN FIBROMYALGIA Principal Investigator & Institution: Adler, Gail K.; Assistant Professor; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2001; Project Start 25-SEP-1994; Project End 31-JUL-2003 Summary: (Adapted From Applicant's Abstract) This competitive renewal project proposes to extend studies of the hypothalamic-pituitary-adrenal axis in fibromyalgia syndrome previously undertaken by the PI. Her initial data suggested reduced adrenocorticotropin (ACTH) and epinephrine responses to graded hypoglycemic challenge, and blunting of the normal diurnal cortisol rhythm in patients with fibromyalgia when compared to normal controls. The PI postulates that the decreased ACTH response to hypoglycemic challenge is the result of impaired CRH release, this also results in decreased sympathoadrenal response to hypoglycemia. The PI further proposes that the diurnal cortisol rhythm in patients with fibromyalgia is abnormal due to a shift in the circadian phase. In Specific Aim 1, the PI and her colleagues propose to assess hypothalamic CRH-pituitary ACTH activity at baseline and in response to three stimuli: hypoglycemia, metapyrone-induced glucocorticoid administration, and an immune stimulus with tetanus toxoid vaccine. In Specific Aim 2, sypathoadrenal responses to hypoglycemia, the cold pressor test, metapyrone vs. placebo will be compared in patients with fibromyalgia and controls. In Specific Aim 3, the circadian phase (measured by core body temperature and melatonin levels) will be compared in women with fibromyalgia and healthy controls. Additional studies of the relationship between disrupted sleep pattern and night-time secretion of ACTH and cortisol and cytokines are planned if the circadian phase is not shifted. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: REGULATION OF KIR CHANNELS IN RETINAL GLIAL CELLS Principal Investigator & Institution: Eaton, Misty J.; Assistant Professor; Universidad Central Del Caribe Bayamon, Pr 009606032 Timing: Fiscal Year 2002; Project Start 01-AUG-1994; Project End 31-DEC-2005 Summary: Potassium inwardly rectifying channels (Kir) stabilize the membrane potential and carry K+ ions. Kir are dominant in the astrocytic Muller (glial) cells responsible for maintaining extracellular homeostasis in the retina. Excitation of neurons increases levels of extracellular potassium ions (K+) at synapses, which if uncorrected would result in depolarization of neurons and a loss of synaptic transmission. Kir channels serve to equaliz4e intraretinal K+ gradients by a mechanism called spatial buffering or K" siphoning. Glial cells carry K+ currents inward in regions where the extracellular K+ concentration is increased and outward at more distant regions. In order to extrude K+ in distant regions, Muller cells need either one type of Kir with rectification that can be quickly regulated (to have outward current) or to have express additional Kir channels with weak or little rectification. The only Kir described in Muller cells to date is Kir 4.1. This channel is strongly rectifying and requires ATP to function and, thereby, could not function for K+ siphoning or when ATP is depleted (i.e.,
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anoxia.). Our preliminary data demonstrate the existence of another Kir subunit, Kir 6.1 (KATP) expressed in Muller cells, which may complete the above- mentioned requirements. Our working hypothesis is that there are two possible ways of how these different subunits (Kir4.1 AND Kir6.1) may collaborate in Muller cell functioning, (i) by co-expression in functional heteromers, or (ii) by mutual switching between two distinct homomeric channels. Our long-term goal is to determine the identify and regulation of Kir channels from retinal glial cells. This will be accomplished using a multi-faceted approach. (1) By determining which Kir subunits are expressed in retinal Muller (glial) cells using immunocytochemistry. (2) By determining the electrophysiological properties and regulation by ATP, spermine and pH of homomeric and heteromeric channels expressed in HEK cells. (3) The electrophysiological properties and regulation of Kir channels and dissociated Muller cells will be compared with the expressed channels and will be examined under different metabolic conditions. The results of these studies will provide insight into normal Kir channel function as well as Kir channel regulation during anoxia and hypoglycemia. when ATP is depleted. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: STRUCTURAL DETERMINANTS OF PIP2 REGULATION Principal Investigator & Institution: Logothetis, Diomedes E.; Associate Professor; Physiology and Biophysics; Mount Sinai School of Medicine of Nyu of New York University New York, Ny 10029 Timing: Fiscal Year 2002; Project Start 01-APR-1998; Project End 31-MAR-2006 Summary: (provided by applicant): Kir channels serve important functional roles in cellular physiology: Kir6 channels control insulin secretion, myocardial resistance to hypoxia and protection against hypoxia-induced generalized seizure; Kir3 channels mediate the vagal control of heart rate and contribute to the G protein mediated regulation of neurotransmitter release in the brain; Kirl channels control K+ secretion in kidney; Kir4 channels in glial cells and inner ear control K+ homeostasis and excitability. In humans there are three major diseases linked so far to mutations in a Kir channel or an associated protein: persistent hyperinsulinimic hypoglycemia of infancy (Kir6,2), Barter's syndrome (Kir1.1), and Andersen's syndrome (Kir2.1). In addition, the weaver phenotype, a neurological disorder in mice has also been associated with mutations in a Kir3 channel. A common characteristic of members of the inward rectifier K+ (Kir) channel family is that they are all activated by the plasma membrane phospholipid PIP2, phosphatidylinositol-bis-phosphate. Differences in channel-PIP2 interactions have been described among specific Kir members both biochemically and functionally. Channels that experience strong interactions with PIP2 are highly active and are not normally inhibited by PIP2 hydrolysis, presumably because the PIP2 that interacts with these channels is protected from hydrolyzing enzymes (e.g. Kir2.1). Channels that experience intermediate strength of interaction with PIP2 show also intermediate levels of activity relative to other family members and they can indeed be inhibited by signals that lead to PIP2 hydrolysis (e.g. Kir2.3). Finally, channels that interact weakly with PIP2 require a gating molecule to strengthen channel-PIP2 interactions in order to be activated. These channels are highly susceptible to inhibition by signals that lead to PIP2 hydrolysis (e.g. Kir3.4). Regulation of channel activity by phosphorylation depends on channel-PIP2 interactions. Several of the mutations that result in disease involve PIP2-interacting residues. Since the activity and its regulation is so critically dependent on interactions with PIP2 in Kir channels, and since mutations that affect channel-PIP2 interactions result in disease, it is clear that understanding in detail the mechanisms responsible for channel-PIP2 interactions and their regulation is of paramount importance in molecular
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medicine. The current proposal aims to find answers to the following three questions. (a) What are the general and specific structural determinants that dictate the strength of interactions of each Kir family member with PIP2? (b) What are the sites of action of PKA/PKC-dependent phosphorylation and what is their relation to specific channelPIP2 interacting sites? and (c) Which are the structural determinants that explain differences in stereospecific interactions of each Kir family member with PIP2? Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: THE ROLE OF ADENOSINE IN HYPOGLYCEMIC BRAIN INJURY Principal Investigator & Institution: Rivkees, Scott A.; Associate Professor; Pediatrics; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-JUL-2004 Summary: (provided by applicant): Acute episodes of hypoglycemia are associated with long-term neurological injury, and it has been suggested that the developing brain may be more sensitive to the adverse affects of hypoglycemia. Potential mediators of hypoglycemia in the brain include adenosine. However, our understanding of the role that adenosine plays in hypoglycemia-induced brain injury is limited, as is our understanding of the developmental susceptibility of the brain to hypoglycemic damage. We have recently found that acute hypoglycemia (1.5 mM; 27 mg/dl; 6-12 hrs) results in much more neuronal death in younger than in older animals. In addition, we find that blockade of A1 adenosine receptor (A1AR) action reduces hypoglycemiainduced neuronal death. We also find that hypoglycemia leads to both neuronal and oligodendrocyte injury, possibly due to perturbations in intracellular Ca2+ signaling. Based on these observations, we hypothesize (a) that the developing brain is especially sensitive to the adverse effects of low glucose levels, (b) hypoglycemia leads to increased AIAR action, resulting in neuronal and oligodendrocyte injury, and (c) A1AR antagonists will reduce hypoglycemic brain injury. To test these hypotheses, (1) we will examine the developmental susceptibility of the brain to hypoglycemic injury. (2) We will assess the roles of A1ARs in mediating hypoglycemic injury. (3) We will examine mechanisms of hypoglycemic injury in neurons, and (4) oligodendrocytes. In many previous studies of hypoglycemia, non-physiological paradigms have been used that include the combination of hypoxia and hypoglycemia, aglycemia, or extended hypoglycemia. Thus, to provide insights into the effects of hypoglycemia, we will examine responses to glucose levels associated with clinical hypoglycemia (0.75-3 mM), without hypoxia or other metabolic insults. We will also focus on short-term, low glucose exposure. We anticipate that these studies will yield new insights into the mechanisms of hypoglycemic brain injury and may lead to the development of practical strategies for reducing hypoglycemic brain injury. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: TRAFFICKING SIGNALS ON KATP CHANNELS SUBUNITS Principal Investigator & Institution: Aguilar-Bryan, Lydia; Assistant Professor; Medicine; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2001; Project Start 15-FEB-2001; Project End 31-JAN-2005 Summary: The pancreatic beta-cell isoform of KATP channels, consisting of SURI and KIR6.2 subunits, plays a key role in coupling glucose metabolism to membrane electrical activity. Mutations in either subunit can cause a recessive form of neonatal hypoglycemia termed persistent hyperinsulinemic hypoglycemia of infancy, or PHHI. Recent work has shown that both subunits have trafficking signals. SURI and KIR6.2
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have endoplasmic reticulum (ER) retention signals, while we have established that the C-terminus of SURI has an additional signal, which is required for surface expression even in the absence of the ER retention signals. The ER retention signals are 'masked' during channel assembly, and together these two sets of signals act as a quality control mechanism to insure that only completely assembled channels, (SUR1/KIR6.2)4, with both nucleotide-binding folds intact reach the cell surface. A number of PHHI mutations truncate SURI; it is proposed that these deletions remove the C-terminal signal and that the SURIAC channels then fail to reach the cell surface, which accounts for the observed loss of channel activity. The nature of these recently discovered trafficking signals, how they function, and what proteins they interact with is not understood. The objective of this application is to study the role of membrane trafficking in the correct surface expression of KATP channels by determining how the SURI C-terminal 'anterograde' signal works, specifically the investigators propose to: 1. Determine if removal of the SURI C-terminal signal results in increased rates of degradation or targeting to different degradation pathways. 2. Identify "receptor(s)" that may mediate the activity of the SURI carboxyl terminus. 3. Examine the behavior of SURI missense mutations that we have shown exhibit trafficking defects. 4. Characterize the order of assembly of KATP channel sub-units. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PROLIFERATION
TRANSCRIPTIONAL
CONTROL
IN
HEPATOCYTE
Principal Investigator & Institution: Greenbaum, Linda E.; Medicine; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2001; Project Start 21-SEP-2001; Project End 31-JUL-2006 Summary: (provided by applicant): The adult liver has a remarkable capacity to restore its mass in response to partial hepatectomy, liver transplantation, or toxic or inflammatory injury. Regeneration after partial hepatectomy is impaired in CCAAT enhancer binding protein beta(C/EBP-beta) -/- mice and is associated with decreased hepatocyte DNA synthesis, prolonged hypoglycemia and reduced expression of growth-associated and cell cycle-associated genes, including cyclin E. Resistance to Fasmediated apoptotic injury in C/EBP-beta -/- livers also links C/EBP-beta to the regulation of the initial liver injury response. Physiologic associations between C/EBPalpha and beta and the retinoblastoma protein in other cell types and the finding that pRb phosphorylation is decreased in C/EBP-beta -/- livers after partial hepatectomy link C/EBP-beta with pRb phosphorylation, cyclin E activation and hepatocyte cell cycle progression. Phosphorylation of specific domains in the C/EBP-beta protein overrides the block to cell cycle progression associated with induction of unmodified C/EBP-beta in cell models, suggesting that posttranslational modifications of C/EBP-beta are also necessary for hepatocyte cell cycle progression in the regenerating liver. The Specific Aims of this proposal are (1) To identify the component(s) of the apoptotic pathway that are abnormally regulated in Fas-antibody treated C/EBP-beta -/- livers and to determine if C/EBP-beta is also involved in the regulation of TNF-alpha mediated apoptotic liver injury. (2) To determine whether C/EBP-beta and/or C/EBP-alpha interactions with pRb are important for pRb phosphorylation, cyclin E activation and hepatocyte cell cycle progression. (3) To define the C/EBP-beta functional domains that are required for hepatocyte proliferation. C/EBP-beta proteins modified at residues that correspond to phosphoacceptor sites linked to signaling pathways in the regenerating liver will be introduced into CIEBP-beta -/- primary hepatocytes and assessed for their ability to facilitate hepatocyte cell cycle progression. Together these studies will provide
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important mechanistic insights regarding the basis for the response of the liver to injury and for hepatocyte proliferation following growth stimulation. This knowledge will be useful for the development of therapeutics to augment the regenerative capacity of the liver in a variety of liver diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TRANSCRIPTIONAL REGULATION IN NEURONAL INJURY Principal Investigator & Institution: Dawson, Ted M.; Professor; Neurology; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2001; Project Start 16-SEP-1997; Project End 31-JUL-2003 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: TREATMENT PREFERENCES OF OLDER PATIENTS WITH DIABETES Principal Investigator & Institution: Chin, Marshall H.; Associate Professor; Medicine; University of Chicago 5801 S Ellis Ave Chicago, Il 60637 Timing: Fiscal Year 2001; Project Start 15-AUG-2000; Project End 31-JUL-2003 Summary: Diabetes is an excellent chronic disease model for studying provider-patient communication and complex decision-making in older persons, because patient preferences, clinical judgment, and incomplete scientific evidence should be incorporated into the discussion. While approximately 40 percent of the patients with diabetes in the United States are 65 years or older, limited evidence exists to guide their management. In younger populations, tight glycemic control has been demonstrated to prevent microvascular complications such as retinopathy and nephropathy. However, older patients may die of other causes before developing diabetic complications. Given that the treatment of diabetes can adversely affect quality of life through dietary restrictions, the burden of taking medications, hypoglycemia, and the discomfort of insulin injections, treatment should have more benefit than harm. Therefore, it is crucial to understand patient preferences regarding the aggressiveness of treatment. The ultimate goal of this research program is to improve doctor- patient communication about the issues relevant to diabetes care of older persons through provider and patient educational tools that can be used in routine daily clinical practice. The specific aims in this study of 600 patients with diabetes aged 65 years or older are: 1) to assess older patients' preferences regarding the aggressiveness of their diabetes treatment; 2) to identify the factors associated with the aggressiveness of patients' preferences for diabetes care; and 3) to determine the concordance between older patients' preferences and physicians' preferences regarding the aggressiveness of diabetes care, as well as with actual treatment style. Quantitative interviews will measure patient utilities for diabetic complications and intensity of therapy through the time trade-off technique. The interview will also use validated scales to measure the patient's view of different domains of the Health Belief Model including: 1) vulnerability to the ill effects of diabetes; 2) severity of diabetes as a disease and illness; 3) benefits of treatment; and 4) barriers to treatment. Physicians will be surveyed about their preference for individual patient's aggressiveness of therapy, and the actual treatment style will be obtained from the medical record. These data sources will supply a comprehensive view of the factors influencing a patient's preferences for aggressiveness of diabetes treatment, and enable the patient's choices to be compared with those of physicians and actual medical practice.
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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: VALIDATION OF LONG-TERM GLUCOSE SENSOR IN TISSUES Principal Investigator & Institution: Gough, David A.; Professor and Chair; Bioengineering; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, Ca 92093 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2005 Summary: (provided by applicant): There is an urgent need for a new glucose sensor that is: (1) highly reliable and continuous; (2) capable of automatic function, independent of user initiative, to warn of hypoglycemia; and (3) acceptable to users. We have an implantable electrochemical glucose sensor that can potentially meet this need. A prototype of this sensor has operated continuously as a central venous implant in dogs for over 100 days without the need for recalibration and now in humans for over one year. This achievement still represents the published world's record for implanted glucose sensor longevity. For reasons of safety, we are designing a tissue glucose sensor for long-term use in humans. The implant will include the sensor, electronics and telemetry, antenna, and battery. Glucose signals will be transmitted to an external receiver resembling a beeper that will display the actual glucose value and function as a hypoglycemia alarm. Our recent studies have focused on developing a complete understanding of the tissue sensor response to blood glucose. The working hypothesis is: "A useful analytical relationship exists between the signal of sensors implanted in tissue and blood glucose concentration." We have: defined sensor performance requirements, developed methods of sensor fabrication, implanted sensors in a welldefined hamster model, established novel confocal microscopy methods for nondestructive visualization of the tissue/sensor interface, and modeled sensor response. We will extend our studies by implanting sensors in pigs and carry out extensive analysis of sensor system dynamics, including development of a method for sensor recalibration, further documentation of implant biocompatibility, and establishment of system reliability. These studies will be carded out in addition to our continuing studies in hamsters and diabetic rats. These studies set the stage for trials in humans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: YALE CENTER IN THE CHILDREN'S GLUCOSE SENSOR NETWORK Principal Investigator & Institution: Tamborlane, William V.; Professor of Pediatrics; Pediatrics; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-AUG-2006 Summary: (prepared by applicant): Results of the Diabetes Control and Complications Trial indicate that most patients with type 1 diabetes (T1DM) should receive intensive treatment to lower the risk of microvascular and neuropathic complications. It has been shown that strict diabetes control can be achieved in youth with T1DM but at the expense of unacceptably high frequency of severe hypoglycemic events, especially in younger patients. Moreover, pilot studies using new continuous glucose sensoring systems in youth with T1DM indicate that many glucose swings from high to low values are asymptomatic and are not detected by self blood glucose monitoring (SBGM). Thus the investigators are submitting an application to be a center in the Type 1 Diabetes in Children Research Network to evaluate the utility of continuous glucose monitoring devices in improving diabetes control and preventing hypoglycemia in youth with T1DM. As a first step, the investigators are proposing to validate the accuracy of the MiniMed Continuous Glucose Monitoring System (CGMS) in children with and without
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T1DM against frequent blood glucose measurements in an inpatient Clinic and Research Center setting. Next, the CGMS will be used in a large, cross-sectional study to characterize and compare the frequency and severity of hypo and hyperglycemia by age (pre-school versus school age versus adolescents), type of insulin treatment (injections versus pump), and by HbA1c level (within target versus above target). Validation and cross-sectional studies will also provide the opportunity to test the effectiveness of current management guidelines regarding carbohydrate counting and the composition of bedtime snacks, as well as the impact of afternoon exercise on nocturnal hypoglycemia. The investigators are also proposing a randomized, prospective clinical trial to examine whether repeated use of the CGMS every six weeks for 24 weeks in conjunction with conventional SBGM is more effective than SBGM alone in improving diabetes control, lowering the risk for hypoglycemia, and reducing patient?s and parents? anxiety and fears of hypoglycemia. The introduction of new methods of continuous glucose sensoring promises to be the most important advance in therapy of T1DM in the past 20 years. The resources for clinical research and the expertise in the Network will also allow the investigators to assess the usefulness for children with T1DM of current and future glucose sensoring systems in a scientifically rigorous and timely manner. 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 “hypoglycemia” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for hypoglycemia in the PubMed Central database: •
Adaptation in Brain Glucose Uptake Following Recurrent Hypoglycemia. by Boyle PJ, Nagy RJ, O'Connor AM, Kempers SF, Yeo RA, Qualls C.; 1994 Sep 27; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=44810
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Anti-gamma interferon and anti-interleukin-6 antibodies affect staphylococcal enterotoxin B-induced weight loss, hypoglycemia, and cytokine release in Dgalactosamine-sensitized and unsensitized mice. by Matthys P, Mitera T, Heremans H, Van Damme J, Billiau A.; 1995 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=173128
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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Defective trafficking and function of KATP channels caused by a sulfonylurea receptor 1 mutation associated with persistent hyperinsulinemic hypoglycemia of infancy. by Cartier EA, Conti LR, Vandenberg CA, Shyng SL.; 2001 Feb 27; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=30234
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Differential Regulation of mRNAs for Nerve Growth Factor, Brain-Derived Neurotrophic Factor, and Neurotrophin 3 in the Adult Rat Brain Following Cerebral Ischemia and Hypoglycemic Coma. by Lindvall O, Ernfors P, Bengzon J, Kokaia Z, Smith M, Siesjo BK, Persson H.; 1992 Jan 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=48296
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Primacy of Liver Glucosensors in the Sympathetic Response to Progressive Hypoglycemia. by Donovan CM, Hamilton-Wessler M, Halter JB, Bergman RN.; 1994 Mar 29; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=43471
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Primary Role of Interleukin-1[alpha] and Interleukin-1[beta] in LipopolysaccharideInduced Hypoglycemia in Mice. by Oguri S, Motegi K, Iwakura Y, Endo Y.; 2002 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130127
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Serum "Big Insulin-Like Growth Factor II" from Patients with Tumor Hypoglycemia Lacks Normal E-Domain O-Linked Glycosylation, a Possible Determinant of Normal Propeptide Processing. by Daughaday WH, Trivedi B, Baxter RC.; 1993 Jun 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=46815
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Stabilization of vascular endothelial growth factor mRNA by hypoxia and hypoglycemia and coregulation with other ischemia-induced genes. by Stein I, Neeman M, Shweiki D, Itin A, Keshet E.; 1995 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=230785
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 hypoglycemia, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “hypoglycemia” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for hypoglycemia (hyperlinks lead to article summaries): 6 PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.
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67-year-old woman with recurrent hypoglycemia. Author(s): McDermott JH, Kent PD, Service FJ. Source: Mayo Clinic Proceedings. 2001 September; 76(9): 939-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11560306&dopt=Abstract
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A 12-day-old infant with hypoglycemia. Author(s): Louis C, Weinzimer SA. Source: Current Opinion in Pediatrics. 2003 June; 15(3): 333-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12806266&dopt=Abstract
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A case of severe hypoglycemia due to pimobendan. Author(s): Ako J, Eto M, Watanabe T, Ouchi Y. Source: International Journal of Cardiology. 2001 August; 80(1): 83-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11575266&dopt=Abstract
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A randomized study comparing blood glucose control and risk of severe hypoglycemia achieved by non-programmable versus programmable external insulin pumps. Author(s): Catargi B, Breilh D, Gin H, Rigalleau V, Saux MC, Roger P, Tabarin A. Source: Diabetes & Metabolism. 2001 June; 27(3): 323-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11431597&dopt=Abstract
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A young woman with persistent hypoglycemia, rhabdomyolysis, and coma: recognizing fatty acid oxidation defects in adults. Author(s): Kluge S, Kuhnelt P, Block A, Merkel M, Gocht A, Lukacs Z, Kohlschutter A, Kreymann G. Source: Critical Care Medicine. 2003 April; 31(4): 1273-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12682504&dopt=Abstract
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ABCC8 (SUR1) and KCNJ11 (KIR6.2) mutations in persistent hyperinsulinemic hypoglycemia of infancy and evaluation of different therapeutic measures. Author(s): Darendeliler F, Fournet JC, Bas F, Junien C, Gross MS, Bundak R, Saka N, Gunoz H. Source: J Pediatr Endocrinol Metab. 2002 July-August; 15(7): 993-1000. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12199344&dopt=Abstract
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Abnormal glucose handling by the kidney in response to hypoglycemia in type 1 diabetes. Author(s): Cersosimo E, Garlick P, Ferretti J. Source: Diabetes. 2001 September; 50(9): 2087-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11522675&dopt=Abstract
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Absence of adverse effects of severe hypoglycemia on cognitive function in schoolaged children with diabetes over 18 months. Author(s): Wysocki T, Harris MA, Mauras N, Fox L, Taylor A, Jackson SC, White NH. Source: Diabetes Care. 2003 April; 26(4): 1100-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12663580&dopt=Abstract
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Acarbose treatment of postprandial hypoglycemia in children after Nissen fundoplication. Author(s): Ng DD, Ferry RJ Jr, Kelly A, Weinzimer SA, Stanley CA, Katz LE. Source: The Journal of Pediatrics. 2001 December; 139(6): 877-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11743518&dopt=Abstract
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Acute and prolonged effects of insulin-induced hypoglycemia on the pituitarythyroid axis in humans. Author(s): Schultes B, Oltmanns KM, Kern W, Born J, Fehm HL, Peters A. Source: Metabolism: Clinical and Experimental. 2002 October; 51(10): 1370-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12370861&dopt=Abstract
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Acute hypoglycemia impairs the functioning of the central but not peripheral nervous system. Author(s): Strachan MW, Deary IJ, Ewing FM, Ferguson SS, Young MJ, Frier BM. Source: Physiology & Behavior. 2001 January; 72(1-2): 83-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11239984&dopt=Abstract
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Acute hypoglycemia in humans causes attentional dysfunction while nonverbal intelligence is preserved. Author(s): McAulay V, Deary IJ, Ferguson SC, Frier BM. Source: Diabetes Care. 2001 October; 24(10): 1745-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11574436&dopt=Abstract
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Administration of neutral protamine Hagedorn insulin at bedtime versus with dinner in type 1 diabetes mellitus to avoid nocturnal hypoglycemia and improve control. A randomized, controlled trial. Author(s): Fanelli CG, Pampanelli S, Porcellati F, Rossetti P, Brunetti P, Bolli GB. Source: Annals of Internal Medicine. 2002 April 2; 136(7): 504-14. Summary for Patients In: http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11926785&dopt=Abstract
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Adult-onset nesidioblastosis causing hypoglycemia: an important clinical entity and continuing treatment dilemma. Author(s): Witteles RM, Straus II FH, Sugg SL, Koka MR, Costa EA, Kaplan EL. Source: Archives of Surgery (Chicago, Ill. : 1960). 2001 June; 136(6): 656-63. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11387003&dopt=Abstract
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Alcohol and glucose counterregulation during acute insulin-induced hypoglycemia in type 2 diabetic subjects. Author(s): Rasmussen BM, Orskov L, Schmitz O, Hermansen K. Source: Metabolism: Clinical and Experimental. 2001 April; 50(4): 451-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11288041&dopt=Abstract
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Alcohol induced ketoacidosis, severe hypoglycemia and irreversible encephalopathy. Author(s): Jain H, Beriwal S, Singh S. Source: Medical Science Monitor : International Medical Journal of Experimental and Clinical Research. 2002 November; 8(11): Cs77-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12444383&dopt=Abstract
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Alteration of the counterregulatory responses to insulin-induced hypoglycemia and of cognitive function after massive weight reduction in severely obese subjects. Author(s): Guldstrand M, Ahren B, Wredling R, Backman L, Lins PE, Adamson U. Source: Metabolism: Clinical and Experimental. 2003 July; 52(7): 900-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12870168&dopt=Abstract
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Antepartum findings and obstetric aspects in pregnancies followed by neonatal persistent hyperinsulinemic hypoglycemia. Author(s): Parviainen AM, Puolakka J, Kirkinen P. Source: American Journal of Perinatology. 2002 April; 19(3): 163-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12012292&dopt=Abstract
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Antibodies directed against the E region of pro-insulin-like growth factor-II used to evaluate non-islet cell tumor-induced hypoglycemia. Author(s): van Doorn J, Hoogerbrugge CM, Koster JG, Bloemen RJ, Hoekman K, Mudde AH, van Buul-Offers SC. Source: Clinical Chemistry. 2002 October; 48(10): 1739-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12324491&dopt=Abstract
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Anti-insulin receptor autoantibodies in a patient with type B insulin resistance and fasting hypoglycemia. Author(s): Yamasaki H, Yamaguchi Y, Fujita N, Kato C, Kuwahara H, Yamauchi MD, Yamakawa K, Abe T, Ozaki M, Sera Y, Uotani S, Kawasaki E, Takino H, Eguchi K. Source: Acta Diabetologica. 2000; 37(4): 189-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11450502&dopt=Abstract
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Arachidonate release and c-fos expression in various models of hypoxia and hypoxiahypoglycemia in retinoic acid differentiated neuroblastoma cells. Author(s): Petroni A, Papini N, Blasevich M, Rise P, Galli C. Source: Neurochemistry International. 2002 March; 40(3): 255-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11741009&dopt=Abstract
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Atypical presentation of silent nocturnal hypoglycemia in an older person. Author(s): Alagiakrishnan K, Lechelt K, McCracken P, Torrible S, Sclater A. Source: Journal of the American Geriatrics Society. 2001 November; 49(11): 1577-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11890609&dopt=Abstract
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Autoimmune hypoglycemia presenting as seizure one week after surgery. Author(s): Vogeser M, Parhofer KG, Furst H, Jacob K, Brodl UC, Seidel D. Source: Clinical Chemistry. 2001 April; 47(4): 795-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11274047&dopt=Abstract
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Avoidance of hypoglycemia restores hypoglycemia awareness by increasing betaadrenergic sensitivity in type 1 diabetes. Author(s): Fritsche A, Stefan N, Haring H, Gerich J, Stumvoll M. Source: Annals of Internal Medicine. 2001 May 1; 134(9 Pt 1): 729-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11329230&dopt=Abstract
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Avoiding nocturnal hypoglycemia: consideration of an extra injection at bedtime. Author(s): Norris AW, Laffel LM. Source: Annals of Internal Medicine. 2002 April 2; 136(7): 547-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11926791&dopt=Abstract
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Beta-blockers, diabetes, and hypoglycemia: risky business? Author(s): Levinson PD. Source: Medicine and Health, Rhode Island. 2001 March; 84(3): 81-2. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11280134&dopt=Abstract
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Blood genomic responses differ after stroke, seizures, hypoglycemia, and hypoxia: blood genomic fingerprints of disease. Author(s): Tang Y, Lu A, Aronow BJ, Sharp FR. Source: Annals of Neurology. 2001 December; 50(6): 699-707. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11761467&dopt=Abstract
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Blood-to-brain glucose transport, cerebral glucose metabolism, and cerebral blood flow are not increased after hypoglycemia. Author(s): Segel SA, Fanelli CG, Dence CS, Markham J, Videen TO, Paramore DS, Powers WJ, Cryer PE. Source: Diabetes. 2001 August; 50(8): 1911-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11473055&dopt=Abstract
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Carcinoid syndrome, acromegaly, and hypoglycemia due to an insulin-secreting neuroendocrine tumor of the liver. Author(s): Furrer J, Hattenschwiler A, Komminoth P, Pfammatter T, Wiesli P. Source: The Journal of Clinical Endocrinology and Metabolism. 2001 May; 86(5): 2227-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11344231&dopt=Abstract
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Cardiac responses to insulin-induced hypoglycemia in nondiabetic and intensively treated type 1 diabetic patients. Author(s): Russell RR 3rd, Chyun D, Song S, Sherwin RS, Tamborlane WV, Lee FA, Pfeifer MA, Rife F, Wackers FJ, Young LH. Source: American Journal of Physiology. Endocrinology and Metabolism. 2001 November; 281(5): E1029-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11595660&dopt=Abstract
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Case of pseudohypoglycemia. Author(s): Rushakoff RJ, Lewis SB. Source: Diabetes Care. 2001 December; 24(12): 2157-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11723104&dopt=Abstract
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Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 39-2001. A newborn girl with seizures and persistent hypoglycemia. Author(s): Sadeghi-Nejad A, Graeme-Cook FM. Source: The New England Journal of Medicine. 2001 December 20; 345(25): 1833-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11752361&dopt=Abstract
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Case report: hypoglycemia and diffusion-weighted imaging. Author(s): Chan R, Erbay S, Oljeski S, Thaler D, Bhadelia R. Source: Journal of Computer Assisted Tomography. 2003 May-June; 27(3): 420-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12794609&dopt=Abstract
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Case report: liver glycogen synthase deficiency--a cause of ketotic hypoglycemia. Author(s): Rutledge SL, Atchison J, Bosshard NU, Steinmann B. Source: Pediatrics. 2001 August; 108(2): 495-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11483824&dopt=Abstract
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Case report: somatostatin producing teratoma, causing rapidly alternating extreme hyperglycemia and hypoglycemia, and ovarian somatostatinoma. Author(s): Gregersen G, Holst JJ, Trankjaer A, Stadil F, Mogensen AM. Source: Metabolism: Clinical and Experimental. 2002 September; 51(9): 1180-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12200764&dopt=Abstract
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Celiac disease in children and adolescents with type I diabetes: importance of hypoglycemia. Author(s): Mohn A, Cerruto M, Lafusco D, Prisco F, Tumini S, Stoppoloni O, Chiarelli F. Source: Journal of Pediatric Gastroenterology and Nutrition. 2001 January; 32(1): 37-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11176322&dopt=Abstract
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Central pontine myelinolysis and myocardial infarction following severe hypoglycemia. Author(s): Purucker E, Nguyen HN, Lammert F, Koch A, Matern S. Source: Intensive Care Medicine. 2000 September; 26(9): 1406-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11089780&dopt=Abstract
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Cerebellar ataxia after repeated hypoglycemia. Author(s): Schwaninger M, Haehnel S, Hess K, Fohr B, Nawroth P, Hacke W. Source: European Journal of Neurology : the Official Journal of the European Federation of Neurological Societies. 2002 September; 9(5): 544-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12220391&dopt=Abstract
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Cerebral damage due to neonatal hypoglycemia. Author(s): Avenarius HA, Versteege CW, Engelshove HA. Source: Jbr-Btr. 2003 May-June; 86(3): 136-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12880152&dopt=Abstract
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Changes in regional brain (18)F-fluorodeoxyglucose uptake at hypoglycemia in type 1 diabetic men associated with hypoglycemia unawareness and counter-regulatory failure. Author(s): Cranston I, Reed LJ, Marsden PK, Amiel SA. Source: Diabetes. 2001 October; 50(10): 2329-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11574416&dopt=Abstract
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Characterization of genes encoding the pancreatic beta-cell ATP-sensitive K+ channel in persistent hyperinsulinemic hypoglycemia of infancy in Japanese patients. Author(s): Someya T, Miki T, Sugihara S, Minagawa M, Yasuda T, Kohno Y, Seino S. Source: Endocrine Journal. 2000 December; 47(6): 715-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11228046&dopt=Abstract
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Clinical case seminar: hypoglycemia after pancreas transplantation: association with allograft nesidiodysplasia and expression of islet neogenesis-associated peptide. Author(s): Semakula C, Pambuccian S, Gruessner R, Kendall D, Pittenger G, Vinik A, Seaquist ER. Source: The Journal of Clinical Endocrinology and Metabolism. 2002 August; 87(8): 3548-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12161473&dopt=Abstract
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Cognitive ability and brain structure in type 1 diabetes: relation to microangiopathy and preceding severe hypoglycemia. Author(s): Ferguson SC, Blane A, Perros P, McCrimmon RJ, Best JJ, Wardlaw J, Deary IJ, Frier BM. Source: Diabetes. 2003 January; 52(1): 149-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12502506&dopt=Abstract
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Common variable immunodeficiency with hypoglycemia, Kikuchi lymphadenitis, and hemiparesis in two siblings. Author(s): Chien YH, Yang YH, Hwu WL, Chou CC, Chiang BL. Source: J Microbiol Immunol Infect. 2003 March; 36(1): 65-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12741737&dopt=Abstract
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Continuous subcutaneous insulin infusion in children and adolescents with diabetes mellitus: decreased HbA1c with low risk of hypoglycemia. Author(s): Sulli N, Shashaj B. Source: J Pediatr Endocrinol Metab. 2003 March; 16(3): 393-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12705364&dopt=Abstract
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Cortisol elevations comparable to those that occur during hypoglycemia do not cause hypoglycemia-associated autonomic failure. Author(s): Raju B, McGregor VP, Cryer PE. Source: Diabetes. 2003 August; 52(8): 2083-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12882926&dopt=Abstract
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Cortisol response to arginine-vasopressin does not compare with cortisol response to insulin-hypoglycemia in pituitary tumors. Author(s): Lodha S, Talwar V, Bhansali A, Dash RJ. Source: J Assoc Physicians India. 1998 July; 46(7): 609-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12152842&dopt=Abstract
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Counterregulatory responses to hypoglycemia in patients with glucokinase gene mutations. Author(s): Guenat E, Seematter G, Philippe J, Temler E, Jequier E, Tappy L. Source: Diabetes & Metabolism. 2000 November; 26(5): 377-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11119017&dopt=Abstract
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Counterregulatory responses to hypoglycemia in patients with maturity-onset diabetes of the young caused by HNF-1alpha gene mutations (MODY3). Author(s): Guenat E, Seematter G, Philippe J, Temler E, Jequier E, Tappy L. Source: European Journal of Endocrinology / European Federation of Endocrine Societies. 2001 January; 144(1): 45-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11174836&dopt=Abstract
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Crohn-like enteritis presenting as hypoglycemia in a patient with glycogen storage disease type 1b, treated with granulocyte colony-stimulating factor and splenectomy. Author(s): Barker CC, Butzner JD, Woodman RC, Parsons HG. Source: Journal of Pediatric Gastroenterology and Nutrition. 2001 February; 32(2): 197200. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11321392&dopt=Abstract
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CSE in labor and hypoglycemia. Author(s): Verma SR, Plaat F. Source: Anesthesiology. 2001 June; 94(6): 1150-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11465614&dopt=Abstract
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Defective activation of skeletal muscle and adipose tissue lipolysis in type 1 diabetes mellitus during hypoglycemia. Author(s): Enoksson S, Caprio SK, Rife F, Shulman GI, Tamborlane WV, Sherwin RS. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 April; 88(4): 150311. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12679430&dopt=Abstract
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Detection of hypoglycemia with the GlucoWatch biographer. Author(s): Pitzer KR, Desai S, Dunn T, Edelman S, Jayalakshmi Y, Kennedy J, Tamada JA, Potts RO. Source: Diabetes Care. 2001 May; 24(5): 881-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11347748&dopt=Abstract
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Detection of symptoms by adolescents and young adults with type 1 diabetes during experimental induction of mild hypoglycemia: role of hormonal and psychological variables. Author(s): Ryan CM, Dulay D, Suprasongsin C, Becker DJ. Source: Diabetes Care. 2002 May; 25(5): 852-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11978680&dopt=Abstract
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Do sensor glucose levels accurately predict plasma glucose concentrations during hypoglycemia and hyperinsulinemia? Author(s): Monsod TP, Flanagan DE, Rife F, Saenz R, Caprio S, Sherwin RS, Tamborlane WV. Source: Diabetes Care. 2002 May; 25(5): 889-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11978686&dopt=Abstract
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Doxycycline-induced hypoglycemia in a nondiabetic young man. Author(s): Basaria S, Braga M, Moore WT. Source: Southern Medical Journal. 2002 November; 95(11): 1353-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12540009&dopt=Abstract
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Drug-induced hypoglycemia presenting as acute mountain sickness, after mistaking acetohexamide for acetazolamide. Author(s): Litch JA. Source: Wilderness Environ Med. 1996 August; 7(3): 232-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11990118&dopt=Abstract
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Early brain atrophy in persistent hyperinsulinemic hypoglycemia of infancy. Author(s): Nachum Z, Ben-Shlomo I, Rakover Y, Weiner E, Shalev E. Source: The Journal of Pediatrics. 2002 November; 141(5): 706-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12410202&dopt=Abstract
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Effect of 2 weeks of theophylline on glucose counterregulation in patients with type 1 diabetes and unawareness of hypoglycemia. Author(s): de Galan BE, Tack CJ, Lenders JW, Lutterman JA, Smits P. Source: Clinical Pharmacology and Therapeutics. 2003 July; 74(1): 77-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12844138&dopt=Abstract
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Effect of antecedent hypoglycemia on counterregulatory responses to subsequent euglycemic exercise in type 1 diabetes. Author(s): Galassetti P, Tate D, Neill RA, Morrey S, Wasserman DH, Davis SN. Source: Diabetes. 2003 July; 52(7): 1761-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12829644&dopt=Abstract
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Effect of growth hormone treatment on hypoglycemia in a patient with both hepatic glycogen synthase and isolated growth hormone deficiencies. Author(s): Blumel P, Mullis PE. Source: J Pediatr Endocrinol Metab. 2001 September-October; 14(8): 1151-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11592574&dopt=Abstract
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Effect of near physiologic insulin therapy on hypoglycemia counterregulation in type-1 diabetes. Author(s): Bischof MG, Bernroider E, Ludwig C, Kurzemann S, Kletter K, Waldhausl W, Roden M. Source: Hormone Research. 2001; 56(5-6): 151-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11910200&dopt=Abstract
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Effect of simulated microgravity on endocrine response to insulin-induced hypoglycemia in physically fit men. Author(s): Ksinantova L, Koska J, Kvetnansky R, Marko M, Hamar D, Vigas M. Source: Hormone and Metabolic Research. Hormon- Und Stoffwechselforschung. Hormones Et Metabolisme. 2002 March; 34(3): 155-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11972306&dopt=Abstract
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Effect of structured group education on glycemic control and hypoglycemia in insulin-treated patients. Author(s): Koev DJ, Tankova TI, Kozlovski PG. Source: Diabetes Care. 2003 January; 26(1): 251. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12502698&dopt=Abstract
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Effects of antecedent prolonged exercise on subsequent counterregulatory responses to hypoglycemia. Author(s): Galassetti P, Mann S, Tate D, Neill RA, Costa F, Wasserman DH, Davis SN. Source: American Journal of Physiology. Endocrinology and Metabolism. 2001 June; 280(6): E908-17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11350772&dopt=Abstract
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Effects of hyperglycemia or hypoglycemia on brain cell membrane function and energy metabolism during the immediate reoxygenation-reperfusion period after acute transient global hypoxia-ischemia in the newborn piglet. Author(s): Park WS, Chang YS, Lee M. Source: Brain Research. 2001 May 18; 901(1-2): 102-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11368956&dopt=Abstract
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Effects of morning hypoglycemia on neuroendocrine and metabolic responses to subsequent afternoon hypoglycemia in normal man. Author(s): Davis SN, Tate D. Source: The Journal of Clinical Endocrinology and Metabolism. 2001 May; 86(5): 2043-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11344204&dopt=Abstract
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Effects of oral glucose on systemic glucose metabolism during hyperinsulinemic hypoglycemia in normal man. Author(s): Poulsen PL, Orskov L, Grofte T, Moller J, Holst JJ, Schmitz O, Moller N. Source: Metabolism: Clinical and Experimental. 2000 December; 49(12): 1598-603. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11145123&dopt=Abstract
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Efficacy of therapeutic drug monitoring in prevention of hypoglycemia caused by cibenzoline. Author(s): Takada M, Shibakawa M. Source: European Journal of Clinical Pharmacology. 2001 December; 57(10): 695-700. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11829197&dopt=Abstract
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Elevated endogenous cortisol reduces autonomic neuroendocrine and symptom responses to subsequent hypoglycemia. Author(s): McGregor VP, Banarer S, Cryer PE. Source: American Journal of Physiology. Endocrinology and Metabolism. 2002 April; 282(4): E770-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11882496&dopt=Abstract
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Enteral infusion of glucose at rates approximating EGP enhances glucose disposal but does not cause hypoglycemia. Author(s): Zangeneh F, Basu R, Shah P, Arora P, Camilleri M, Rizza RA. Source: American Journal of Physiology. Endocrinology and Metabolism. 2003 August; 285(2): E280-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12857674&dopt=Abstract
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Epipen as an alternative to glucagon in the treatment of hypoglycemia in children with diabetes. Author(s): Monsod TP, Tamborlane WV, Coraluzzi L, Bronson M, Yong-Zhan T, Ahern JA. Source: Diabetes Care. 2001 April; 24(4): 701-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11315834&dopt=Abstract
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Episodes of severe hypoglycemia in type 1 diabetes are preceded and followed within 48 hours by measurable disturbances in blood glucose. Author(s): Kovatchev BP, Cox DJ, Farhy LS, Straume M, Gonder-Frederick L, Clarke WL. Source: The Journal of Clinical Endocrinology and Metabolism. 2000 November; 85(11): 4287-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11095469&dopt=Abstract
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Establishing the deficiency of glucagon response to hypoglycemia in humans. Author(s): Bolli GB. Source: Endocrine Practice : Official Journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists. 2003 March-April; 9(2): 1645. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12917082&dopt=Abstract
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Estrogen blunts neuroendocrine and metabolic responses to hypoglycemia. Author(s): Sandoval DA, Ertl AC, Richardson MA, Tate DB, Davis SN. Source: Diabetes. 2003 July; 52(7): 1749-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12829642&dopt=Abstract
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Evidence of a linkage between neurocardiogenic dysfunction and reactive hypoglycemia. Author(s): Lerman-Garber I, Valdivia Lopez JA, Flores Rebollar A, Gomez Perez FJ, Antonio Rull J, Hermosillo AG. Source: Revista De Investigacion Clinica; Organo Del Hospital De Enfermedades De La Nutricion. 2000 November-December; 52(6): 603-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11256102&dopt=Abstract
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Exercise hypoglycemia in nondiabetic subjects. Author(s): Brun JF, Dumortier M, Fedou C, Mercier J. Source: Diabetes & Metabolism. 2001 April; 27(2 Pt 1): 92-106. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11353874&dopt=Abstract
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Experience with intravenous glucagon infusions as a treatment for resistant neonatal hypoglycemia. Author(s): Miralles RE, Lodha A, Perlman M, Moore AM. Source: Archives of Pediatrics & Adolescent Medicine. 2002 October; 156(10): 999-1004. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12361445&dopt=Abstract
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Facial appearance in persistent hyperinsulinemic hypoglycemia. Author(s): de Lonlay P, Cormier-Daire V, Amiel J, Touati G, Goldenberg A, Fournet JC, Brunelle F, Nihoul-Fekete C, Rahier J, Junien C, Robert JJ, Saudubray JM. Source: American Journal of Medical Genetics. 2002 August 1; 111(2): 130-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12210338&dopt=Abstract
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Factitious hypoglycemia: a tale from the Arab world. Author(s): Bappal B, George M, Nair R, Khusaiby SA, De Silva V. Source: Pediatrics. 2001 January; 107(1): 180-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11134456&dopt=Abstract
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Fasting hypoglycemia is common during maintenance therapy for childhood acute lymphoblastic leukemia. Author(s): Halonen P, Salo MK, Makipernaa A. Source: The Journal of Pediatrics. 2001 March; 138(3): 428-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11241057&dopt=Abstract
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Focal or diffuse lesions in persistent hyperinsulinemic hypoglycemia of infancy: concerns about interpretation of intraoperative frozen sections. Author(s): Smith VV, Malone M, Risdon RA. Source: Pediatric and Developmental Pathology : the Official Journal of the Society for Pediatric Pathology and the Paediatric Pathology Society. 2001 March-April; 4(2): 138-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11178629&dopt=Abstract
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Frequency of severe hypoglycemia requiring emergency treatment in type 1 and type 2 diabetes: a population-based study of health service resource use. Author(s): Leese GP, Wang J, Broomhall J, Kelly P, Marsden A, Morrison W, Frier BM, Morris AD; DARTS/MEMO Collaboration. Source: Diabetes Care. 2003 April; 26(4): 1176-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12663593&dopt=Abstract
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Fructose amplifies counterregulatory responses to hypoglycemia in humans. Author(s): Gabriely I, Hawkins M, Vilcu C, Rossetti L, Shamoon H. Source: Diabetes. 2002 April; 51(4): 893-900. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11916904&dopt=Abstract
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Functional intensified insulin therapy with short-acting insulin analog: effects on HbA1c and frequency of severe hypoglycemia. An observational cohort study. Author(s): Hartemann-Heurtier A, Sachon C, Masseboeuf N, Corset E, Grimaldi A. Source: Diabetes & Metabolism. 2003 February; 29(1): 53-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12629448&dopt=Abstract
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Gaps in the childhood malaria burden in Africa: cerebral malaria, neurological sequelae, anemia, respiratory distress, hypoglycemia, and complications of pregnancy. Author(s): Murphy SC, Breman JG. Source: The American Journal of Tropical Medicine and Hygiene. 2001 JanuaryFebruary; 64(1-2 Suppl): 57-67. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11425178&dopt=Abstract
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Ghrelin is not necessary for adequate hormonal counterregulation of insulin-induced hypoglycemia. Author(s): Lucidi P, Murdolo G, Di Loreto C, De Cicco A, Parlanti N, Fanelli C, Santeusanio F, Bolli GB, De Feo P. Source: Diabetes. 2002 October; 51(10): 2911-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12351426&dopt=Abstract
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Glucagon infusion for treatment of hypoglycemia: efficacy and safety in sick, preterm infants. Author(s): Charsha DS, McKinley PS, Whitfield JM. Source: Pediatrics. 2003 January; 111(1): 220-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12509583&dopt=Abstract
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Glucagon, catecholamine, and symptom responses to hypoglycemia in living donors of pancreas segments. Author(s): Robertson RP, Sutherland DE, Seaquist ER, Lanz KJ. Source: Diabetes. 2003 July; 52(7): 1689-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12829634&dopt=Abstract
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Glucose monitoring at the arm: risky delays of hypoglycemia and hyperglycemia detection. Author(s): Jungheim K, Koschinsky T. Source: Diabetes Care. 2002 June; 25(6): 956-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12032098&dopt=Abstract
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Glucose transport into brain: effects of hypoglycemia. Author(s): Simpson IA, Vannucci SJ. Source: Diabetes Nutr Metab. 2002 October; 15(5): 281-4; Discussion 284. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12625469&dopt=Abstract
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Growth hormone therapy for non-islet cell tumor hypoglycemia. Author(s): Silveira LF, Bouloux PM, MacColl GS, Camacho-Hubner C, Miraki-Moud F. Source: The American Journal of Medicine. 2002 August 15; 113(3): 255-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12208393&dopt=Abstract
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Growth hormone-releasing hormone facilitates hypoglycemia-induced release of cortisol. Author(s): Perras B, Schultes B, Schwaiger R, Metz C, Wesseler W, Born J, Fehm HL. Source: Regulatory Peptides. 2002 December 31; 110(1): 85-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12468113&dopt=Abstract
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Hemangiopericytoma of the seminal vesicle presenting with hypoglycemia. Author(s): Arya M, Hayne D, Brown RS, O'Donnell PJ, Mundy AR. Source: The Journal of Urology. 2001 September; 166(3): 992. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11490268&dopt=Abstract
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Hodgkin's lymphoma manifesting with hypoglycemia. Author(s): Soares-Welch CV, Zeldenrust SR, Conover CA, Grant CS, Service FJ. Source: Endocrine Practice : Official Journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists. 2003 January-February; 9(1): 96-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12917097&dopt=Abstract
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How low can you go? Chronic hypoglycemia versus normal glucose homeostasis. Author(s): Sood V, Costello BA, Burge MR. Source: Journal of Investigative Medicine : the Official Publication of the American Federation for Clinical Research. 2001 March; 49(2): 205-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11288762&dopt=Abstract
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Hunting for a hypoglycemia gene: severe neonatal hypoglycemia in a consanguineous family. Author(s): Molven A, Rishaug U, Matre GE, Njolstad PR, Sovik O. Source: American Journal of Medical Genetics. 2002 November 15; 113(1): 40-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12400064&dopt=Abstract
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Hyperinsulinemic hypoglycemia associated with possible hypopituitarism in a patient with acquired immunodeficiency syndrome. Author(s): Kim J, Mooradian AD. Source: Endocrine Practice : Official Journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists. 2000 November-December; 6(6): 453-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11155218&dopt=Abstract
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Hyperprolactinemia does not influence hypothalamic-pituitary-adrenocortical function during hypoglycemia in women. Author(s): Imrich R, Rovensky J, Cervenakova Z, Ksinantova L, Kvetnansky R, Koska J. Source: Int J Tissue React. 2002; 24(2): 73-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12182236&dopt=Abstract
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Hypoglycemia after transjugular intrahepatic portosystemic shunt placement in a cirrhotic patient with diabetes mellitus. Author(s): Serin E, Kul K, Ozer B, Gumurdulu Y, Boyacioglu S. Source: Journal of Clinical Gastroenterology. 2002 November-December; 35(5): 409-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12394232&dopt=Abstract
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Hypoglycemia and embryonic heart development. Author(s): Smoak IW. Source: Frontiers in Bioscience : a Journal and Virtual Library. 2002 January 1; 7: D30718. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11779716&dopt=Abstract
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Hypoglycemia and employment/licensure. Author(s): American Diabetes Association. Source: Diabetes Care. 2003 January; 26 Suppl 1: S141. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12502645&dopt=Abstract
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Hypoglycemia and employment/licensure. Author(s): American Diabetes Association. Source: Diabetes Care. 2000 January; 23 Suppl 1: S109. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12017668&dopt=Abstract
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Hypoglycemia and resistance to ketoacidosis in a subject without functional insulin receptors. Author(s): Ogilvy-Stuart AL, Soos MA, Hands SJ, Anthony MY, Dunger DB, O'Rahilly S. Source: The Journal of Clinical Endocrinology and Metabolism. 2001 July; 86(7): 3319-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11443207&dopt=Abstract
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Hypoglycemia and the brain. Author(s): Furlanetto RW. Source: Diabetes Technology & Therapeutics. 2001 Fall; 3(3): 467-516. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11762525&dopt=Abstract
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Hypoglycemia and the breastfed neonate. Author(s): Eidelman AI. Source: Pediatric Clinics of North America. 2001 April; 48(2): 377-87. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11339158&dopt=Abstract
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Hypoglycemia and the full-term newborn: how well does birth weight for gestational age predict risk? Author(s): Johnson TS. Source: Journal of Obstetric, Gynecologic, and Neonatal Nursing : Jognn / Naacog. 2003 January-February; 32(1): 48-57. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12570181&dopt=Abstract
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Hypoglycemia and the hypoglycemic unawareness syndrome. Author(s): Hirsch IB. Source: Diabetes Technology & Therapeutics. 2000; 2 Suppl 1: S81-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11469638&dopt=Abstract
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Hypoglycemia and white matter: pathophysiology of axon injury and role of glycogen. Author(s): Brown AM, Tekkok SB, Ransom BR. Source: Diabetes Nutr Metab. 2002 October; 15(5): 290-3; Discussion 293-4. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12625471&dopt=Abstract
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Hypoglycemia as a predictor of mortality in hospitalized elderly patients. Author(s): Kagansky N, Levy S, Rimon E, Cojocaru L, Fridman A, Ozer Z, Knobler H. Source: Archives of Internal Medicine. 2003 August 11-25; 163(15): 1825-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12912719&dopt=Abstract
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Hypoglycemia associated autonomic failure. Author(s): Diedrich L, Sandoval D, Davis SN. Source: Clinical Autonomic Research : Official Journal of the Clinical Autonomic Research Society. 2002 October; 12(5): 358-65. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12420080&dopt=Abstract
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Hypoglycemia associated with clonidine testing for growth hormone deficiency. Author(s): Huang C, Banerjee K, Sochett E, Perlman K, Wherrett D, Daneman D. Source: The Journal of Pediatrics. 2001 August; 139(2): 323-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11487765&dopt=Abstract
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Hypoglycemia associated with clonidine testing. Author(s): Lanes R. Source: The Journal of Pediatrics. 2002 May; 140(5): 637-8; Author Reply 638. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12032540&dopt=Abstract
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Hypoglycemia associated with the production of insulin-like growth factor II in adrenocortical carcinoma. Author(s): Eguchi T, Tokuyama A, Tanaka Y, Takahashi Y, Kawahara G, Aiba M, Inishi Y, Minowa H. Source: Intern Med. 2001 August; 40(8): 759-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11518119&dopt=Abstract
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Hypoglycemia counterregulation during sleep. Author(s): Gais S, Born J, Peters A, Schultes B, Heindl B, Fehm HL, Werner K. Source: Sleep. 2003 February 1; 26(1): 55-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12627733&dopt=Abstract
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Hypoglycemia due to adrenal suppression secondary to high-dose nebulized corticosteroid. Author(s): Dunlop KA, Carson DJ, Shields MD. Source: Pediatric Pulmonology. 2002 July; 34(1): 85-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12112803&dopt=Abstract
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Hypoglycemia due to nateglinide administration in diabetic patient with chronic renal failure. Author(s): Nagai T, Imamura M, Iizuka K, Mori M. Source: Diabetes Research and Clinical Practice. 2003 March; 59(3): 191-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12590015&dopt=Abstract
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Hypoglycemia in acute lymphoblastic leukemia. Author(s): Collipp PJ. Source: The Journal of Pediatrics. 2002 February; 140(2): 279-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11865292&dopt=Abstract
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Hypoglycemia in cocaine-intoxicated mice. Author(s): Mochson CM, Sharma AN, Hoffman RS. Source: Academic Emergency Medicine : Official Journal of the Society for Academic Emergency Medicine. 2001 July; 8(7): 768. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11435200&dopt=Abstract
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Hypoglycemia in patients with type 2 diabetes mellitus. Author(s): Miller CD, Phillips LS, Ziemer DC, Gallina DL, Cook CB, El-Kebbi IM. Source: Archives of Internal Medicine. 2001 July 9; 161(13): 1653-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11434798&dopt=Abstract
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Hypoglycemia in the newborn. Author(s): Narayan S, Aggarwal R, Deorari AK, Paul VK. Source: Indian J Pediatr. 2001 October; 68(10): 963-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11758134&dopt=Abstract
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Hypoglycemia induced by secretion of high molecular weight insulin-like growth factor-II from a malignant solitary fibrous tumor of the pleura. Author(s): Kishi K, Homma S, Tanimura S, Matsushita H, Nakata K. Source: Intern Med. 2001 April; 40(4): 341-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11334396&dopt=Abstract
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Hypoglycemia prevalence in prepubertal children with type 1 diabetes on standard insulin regimen: use of continuous glucose monitoring system. Author(s): Amin R, Ross K, Acerini CL, Edge JA, Warner J, Dunger DB. Source: Diabetes Care. 2003 March; 26(3): 662-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12610018&dopt=Abstract
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Hypoglycemia probably due to accidental intake of repaglinide. Author(s): Lee IT, Sheu WH, Lin SY. Source: Chang Gung Med J. 2002 November; 25(11): 783-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12553369&dopt=Abstract
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Hypoglycemia rebound migraine. Author(s): Jacome DE. Source: Headache. 2001 October; 41(9): 895-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11703478&dopt=Abstract
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Hypoglycemia risk reduction in type 1 diabetes. Author(s): Cryer PE. Source: Experimental and Clinical Endocrinology & Diabetes : Official Journal, German Society of Endocrinology [and] German Diabetes Association. 2001; 109 Suppl 2: S41223. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11460588&dopt=Abstract
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Hypoglycemia unawareness. Author(s): Tkacs NC. Source: The American Journal of Nursing. 2002 February; 102(2): 34-40; Quiz 41. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11953517&dopt=Abstract
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Hypoglycemia, but not insulin, acutely decreases LH and T secretion in men. Author(s): Oltmanns KM, Fruehwald-Schultes B, Kern W, Born J, Fehm HL, Peters A. Source: The Journal of Clinical Endocrinology and Metabolism. 2001 October; 86(10): 4913-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11600562&dopt=Abstract
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Hypoglycemia, seizures, and pulmonary edema. Author(s): Matz R. Source: Diabetes Care. 2000 November; 23(11): 1715. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11092308&dopt=Abstract
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Hypoglycemia. Author(s): Anthony M. Source: Nursing. 2003 February; 33(2): 88. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12582289&dopt=Abstract
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Hypoglycemia. Author(s): Pourmotabbed G, Kitabchi AE. Source: Obstetrics and Gynecology Clinics of North America. 2001 June; 28(2): 383-400. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11430183&dopt=Abstract
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Hypoglycemia. Pathophysiology and treatment. Author(s): Herbel G, Boyle PJ. Source: Endocrinology and Metabolism Clinics of North America. 2000 December; 29(4): 725-43. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11149159&dopt=Abstract
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Hypoglycemia-associated autonomic failure in advanced type 2 diabetes. Author(s): Segel SA, Paramore DS, Cryer PE. Source: Diabetes. 2002 March; 51(3): 724-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11872673&dopt=Abstract
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Hypoglycemia-associated autonomic failure in diabetes. Author(s): Cryer PE. Source: American Journal of Physiology. Endocrinology and Metabolism. 2001 December; 281(6): E1115-21. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11701423&dopt=Abstract
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Hypoglycemia-induced VEGF expression is mediated by intracellular Ca2+ and protein kinase C signaling pathway in HepG2 human hepatoblastoma cells. Author(s): Park SH, Kim KW, Lee YS, Baek JH, Kim MS, Lee YM, Lee MS, Kim YJ. Source: International Journal of Molecular Medicine. 2001 January; 7(1): 91-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11115615&dopt=Abstract
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Hyponatremia and hypoglycemia in acute Sheehan's syndrome. Author(s): Bunch TJ, Dunn WF, Basu A, Gosman RI. Source: Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology. 2002 October; 16(5): 419-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12587538&dopt=Abstract
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Ibuprofen-related hypoglycemia in a patient receiving sulfonylurea. Author(s): Sone H, Takahashi A, Yamada N. Source: Annals of Internal Medicine. 2001 February 20; 134(4): 344. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11182854&dopt=Abstract
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Impact of bedtime snack composition on prevention of nocturnal hypoglycemia in adults with type 1 diabetes undergoing intensive insulin management using lispro insulin before meals: a randomized, placebo-controlled, crossover trial. Author(s): Kalergis M, Schiffrin A, Gougeon R, Jones PJ, Yale JF. Source: Diabetes Care. 2003 January; 26(1): 9-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12502652&dopt=Abstract
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Impaired blockade of insulin-like growth factor I (IGF-I)-induced hypoglycemia by IGF binding protein-3 analog with reduced ternary complex-forming ability. Author(s): Firth SM, McDougall F, McLachlan AJ, Baxter RC. Source: Endocrinology. 2002 May; 143(5): 1669-76. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11956148&dopt=Abstract
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Impairment of human ether-a-go-go-related gene (HERG) K+ channel function by hypoglycemia and hyperglycemia. Similar phenotypes but different mechanisms. Author(s): Zhang Y, Han H, Wang J, Wang H, Yang B, Wang Z. Source: The Journal of Biological Chemistry. 2003 March 21; 278(12): 10417-26. Epub 2003 January 16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12531891&dopt=Abstract
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Improvement of HbA1c without increased hypoglycemia in adolescents and young adults with type 1 diabetes mellitus treated with recombinant human insulin-like growth factor-I and insulin. rhIGF-I in IDDM Study Group. Author(s): Quattrin T, Thrailkill K, Baker L, Kuntze J, Compton P, Martha P; rhIGF-I in IDDM Study Group. Source: J Pediatr Endocrinol Metab. 2001 March; 14(3): 267-77. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11308044&dopt=Abstract
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Inadvertent sulfonylurea overdosage and hypoglycemia in an elderly woman: failure of serum hypoglycemia screening. Author(s): Earle KE, Rushakoff RJ, Goldfine ID. Source: Diabetes Technology & Therapeutics. 2003; 5(3): 449-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12828829&dopt=Abstract
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Incidence and costs of severe hypoglycemia. Author(s): Holstein A, Plaschke A, Egberts EH. Source: Diabetes Care. 2002 November; 25(11): 2109-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12401771&dopt=Abstract
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Increase in bispectral index (BIS) while correcting a severe hypoglycemia. Author(s): Vivien B, Langeron O, Riou B. Source: Anesthesia and Analgesia. 2002 December; 95(6): 1824-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12456476&dopt=Abstract
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Increasing incidence of serious hypoglycemia in insulin users. Author(s): Johnson ES, Koepsell TD, Reiber G, Stergachis A, Platt R. Source: Journal of Clinical Epidemiology. 2002 March; 55(3): 253-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11864796&dopt=Abstract
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Insights into the biochemical and genetic basis of glucokinase activation from naturally occurring hypoglycemia mutations. Author(s): Gloyn AL, Noordam K, Willemsen MA, Ellard S, Lam WW, Campbell IW, Midgley P, Shiota C, Buettger C, Magnuson MA, Matschinsky FM, Hattersley AT. Source: Diabetes. 2003 September; 52(9): 2433-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12941786&dopt=Abstract
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Insulin and oral hypoglycemic agents should not be used in combination in the treatment of type 2 diabetes. Author(s): Westphal SA, Palumbo PJ. Source: Archives of Internal Medicine. 2003 August 11-25; 163(15): 1783-5; Discussion 1785. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12912711&dopt=Abstract
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Insulin and somatostatin releasing islet cell tumor caused hypoglycemia. Author(s): Karasawa Y, Mochizuki T, Kawa S, Aoki Y, Ueno T, Watanabe T, Kawasaki S, Miyagawa S, Itoh N, Tamai C, Sakurai A, Kiyosawa K. Source: Intern Med. 2001 April; 40(4): 324-30. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11334393&dopt=Abstract
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Insulin detemir is associated with more predictable glycemic control and reduced risk of hypoglycemia than NPH insulin in patients with type 1 diabetes on a basal-bolus regimen with premeal insulin aspart. Author(s): Vague P, Selam JL, Skeie S, De Leeuw I, Elte JW, Haahr H, Kristensen A, Draeger E. Source: Diabetes Care. 2003 March; 26(3): 590-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12610006&dopt=Abstract
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Insulin receptor antibodies inhibit insulin uptake by the liver: in vivo 123I-insulin scintigraphic scanning and in vitro characterization in autoimmune hypoglycemia. Author(s): Dozio N, Sarugeri E, Scavini M, Beretta A, Belloni C, Dosio F, Savi A, Fazio F, Sodoyez-Goffaux F, Pozza G. Source: Journal of Investigative Medicine : the Official Publication of the American Federation for Clinical Research. 2001 January; 49(1): 85-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11217151&dopt=Abstract
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Insulin-like growth factor II-producing intra-abdominal hemangiopericytoma associated with hypoglycemia. Author(s): Matsuda S, Usui M, Sakurai H, Suzuki H, Ogura Y, Shiraishi T. Source: Journal of Gastroenterology. 2001 December; 36(12): 851-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11777215&dopt=Abstract
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Insulinoma induced hypoglycemia in a type 2 diabetic patient. Author(s): Ravnik-Oblak M, Janez A, Kocijanicic A. Source: Wiener Klinische Wochenschrift. 2001 April 30; 113(9): 339-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11388080&dopt=Abstract
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Interactions between hypoglycemia and sleep architecture in children with type 1 diabetes mellitus. Author(s): Pillar G, Schuscheim G, Weiss R, Malhotra A, McCowen KC, Shlitner A, Peled N, Shehadeh N. Source: The Journal of Pediatrics. 2003 February; 142(2): 163-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12584538&dopt=Abstract
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Intraislet hyperinsulinemia prevents the glucagon response to hypoglycemia despite an intact autonomic response. Author(s): Banarer S, McGregor VP, Cryer PE. Source: Diabetes. 2002 April; 51(4): 958-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11916913&dopt=Abstract
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Knowledge of hypoglycemia by primary health care centers registered diabetic patients. Author(s): Elzubier AG. Source: Saudi Med J. 2001 March; 22(3): 219-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11307106&dopt=Abstract
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Lack of mitochondrial trifunctional protein in mice causes neonatal hypoglycemia and sudden death. Author(s): Ibdah JA, Paul H, Zhao Y, Binford S, Salleng K, Cline M, Matern D, Bennett MJ, Rinaldo P, Strauss AW. Source: The Journal of Clinical Investigation. 2001 June; 107(11): 1403-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11390422&dopt=Abstract
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Lantus reduces blood glucose levels, less hypoglycemia in treatment of type 2 diabetes. Author(s): Walczak IM. Source: Diabetes Technology & Therapeutics. 2002; 4(5): 735-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12458566&dopt=Abstract
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Laparoscopic pancreatectomy for persistent hyperinsulinemic hypoglycemia of infancy. Author(s): Blakely ML, Lobe TE, Cohen J, Burghen GA. Source: Surgical Endoscopy. 2001 August; 15(8): 897-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11443431&dopt=Abstract
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Limited impact of vigorous exercise on defenses against hypoglycemia: relevance to hypoglycemia-associated autonomic failure. Author(s): McGregor VP, Greiwe JS, Banarer S, Cryer PE. Source: Diabetes. 2002 May; 51(5): 1485-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11978646&dopt=Abstract
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Losartan attenuates symptomatic and hormonal responses to hypoglycemia in humans. Author(s): Deininger E, Oltmanns KM, Wellhoener P, Fruehwald-Schultes B, Kern W, Heuer B, Dominiak P, Born J, Fehm HL, Peters A. Source: Clinical Pharmacology and Therapeutics. 2001 October; 70(4): 362-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11673752&dopt=Abstract
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Loss of awareness of hypoglycemia temporally associated with selective serotonin reuptake inhibitors. Author(s): Sawka AM, Burgart V, Zimmerman D. Source: Diabetes Care. 2001 October; 24(10): 1845-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11574457&dopt=Abstract
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Malignant solitary fibrous tumor of the pleura causing recurrent hypoglycemia; immunohistochemical stain of insulin-like growth factor i receptor in three cases. Author(s): Chang ED, Lee EH, Won YS, Kim JM, Suh KS, Kim BK. Source: Journal of Korean Medical Science. 2001 April; 16(2): 220-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11306751&dopt=Abstract
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Maternal hypoglycemia during pregnancy in type 1 diabetes: maternal and fetal consequences. Author(s): ter Braak EW, Evers IM, Willem Erkelens D, Visser GH. Source: Diabetes/Metabolism Research and Reviews. 2002 March-April; 18(2): 96-105. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11994900&dopt=Abstract
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Mechanisms of abnormal cardiac repolarization during insulin-induced hypoglycemia. Author(s): Robinson RT, Harris ND, Ireland RH, Lee S, Newman C, Heller SR. Source: Diabetes. 2003 June; 52(6): 1469-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12765959&dopt=Abstract
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Metformin does not adversely affect hormonal and symptomatic responses to recurrent hypoglycemia. Author(s): Fruehwald-Schultes B, Kern W, Oltmanns KM, Sopke S, Toschek B, Born J, Fehm HL, Peters A. Source: The Journal of Clinical Endocrinology and Metabolism. 2001 September; 86(9): 4187-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11549648&dopt=Abstract
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Mini-dose glucagon rescue for hypoglycemia in children with type 1 diabetes. Author(s): Haymond MW, Schreiner B. Source: Diabetes Care. 2001 April; 24(4): 643-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11315823&dopt=Abstract
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Moderate hypoglycemia impairs multiple memory functions in healthy adults. Author(s): Sommerfield AJ, Deary IJ, McAulay V, Frier BM. Source: Neuropsychology. 2003 January; 17(1): 125-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12597081&dopt=Abstract
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Monitoring neonatal hypoglycemia with the Accu-chek advantage II glucose meter: the cautionary tale of galactosemia. Author(s): Newman JD, Ramsden CA, Balazs ND. Source: Clinical Chemistry. 2002 November; 48(11): 2071. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12407002&dopt=Abstract
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Mutations in the sulfonylurea receptor gene in relation to the long-term outcome of persistent hyperinsulinemic hypoglycemia of infancy. Author(s): Taguchi T, Suita S, Ohkubo K, Ono J. Source: Journal of Pediatric Surgery. 2002 April; 37(4): 593-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11912517&dopt=Abstract
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Neonatal glucose metabolism: differential diagnoses, evaluation, and treatment of hypoglycemia. Author(s): Cowett RM, Loughead JL. Source: Neonatal Netw. 2002 June; 21(4): 9-19. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12078323&dopt=Abstract
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Neonatal hyperinsulinemic hypoglycemia. Two case reports. Author(s): Zaffanello M, Zamboni G, Maffeis C, Antoniazzi F, Tato L. Source: Minerva Pediatr. 2002 August; 54(4): 325-33. English, Italian. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12131869&dopt=Abstract
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Neonatal hypoglycemia. Author(s): Perlman D, Southgate WM, Purohit DM. Source: J S C Med Assoc. 2002 June; 98(3): 99-104. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12125200&dopt=Abstract
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Neonates with symptomatic hyperinsulinemic hypoglycemia generate inappropriately low serum cortisol counterregulatory hormonal responses. Author(s): Hussain K, Hindmarsh P, Aynsley-Green A. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 September; 88(9): 4342-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12970308&dopt=Abstract
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Neurologic outcomes of 90 neonates and infants with persistent hyperinsulinemic hypoglycemia. Author(s): Menni F, de Lonlay P, Sevin C, Touati G, Peigne C, Barbier V, Nihoul-Fekete C, Saudubray JM, Robert JJ. Source: Pediatrics. 2001 March; 107(3): 476-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11230585&dopt=Abstract
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No delay in glucose change at antecubital skin in hypoglycemia of normal subjects. Author(s): Nonaka K, Ono F, Ishibashi M, Okita N. Source: Diabetes Care. 2003 March; 26(3): 957-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12610075&dopt=Abstract
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Nocturnal hypoglycemia detected with the Continuous Glucose Monitoring System in pediatric patients with type 1 diabetes. Author(s): Kaufman FR, Austin J, Neinstein A, Jeng L, Halvorson M, Devoe DJ, Pitukcheewanont P. Source: The Journal of Pediatrics. 2002 November; 141(5): 625-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12410189&dopt=Abstract
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Noninsulinoma pancreatogenous hypoglycemia in adults: presentations of two cases. Author(s): Sumarac-Dumanovic M, Micic D, Popovic V. Source: The Journal of Clinical Endocrinology and Metabolism. 2001 May; 86(5): 2328-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11344250&dopt=Abstract
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Noninsulinoma pancreatogenous hypoglycemia syndrome: an update in 10 surgically treated patients. Author(s): Thompson GB, Service FJ, Andrews JC, Lloyd RV, Natt N, van Heerden JA, Grant CS. Source: Surgery. 2000 December; 128(6): 937-44; Discussion 944-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11114627&dopt=Abstract
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Normal growth after administration of octreotide: report on a case of persistent hyperinsulinemic hypoglycemia of infancy treated by continuous subcutaneous injection of octreotide. Author(s): Kuno T, Fujita I, Ohta M, Kanemitsu H, Miyazaki S, Miyamoto S. Source: Endocrine Journal. 1999 March; 46 Suppl: S47-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12054118&dopt=Abstract
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Octreotide as antidote for sulfonylurea-induced hypoglycemia. Author(s): Schier JG, Hirsch ON, Chu J. Source: Annals of Emergency Medicine. 2001 April; 37(4): 417-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11275841&dopt=Abstract
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Octreotide for sulfonylurea-induced hypoglycemia following overdose. Author(s): Carr R, Zed PJ. Source: The Annals of Pharmacotherapy. 2002 November; 36(11): 1727-32. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12398568&dopt=Abstract
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Oral beta-hydroxybutyrate supplementation in two patients with hyperinsulinemic hypoglycemia: monitoring of beta-hydroxybutyrate levels in blood and cerebrospinal fluid, and in the brain by in vivo magnetic resonance spectroscopy. Author(s): Plecko B, Stoeckler-Ipsiroglu S, Schober E, Harrer G, Mlynarik V, Gruber S, Moser E, Moeslinger D, Silgoner H, Ipsiroglu O. Source: Pediatric Research. 2002 August; 52(2): 301-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12149510&dopt=Abstract
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Oral glucose augments the counterregulatory hormone response during insulininduced hypoglycemia in humans. Author(s): Heptulla RA, Tamborlane WV, Ma TY, Rife F, Sherwin RS. Source: The Journal of Clinical Endocrinology and Metabolism. 2001 February; 86(2): 645-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11158023&dopt=Abstract
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Paraneoplastic hypoglycemia associated with a hepatic hemangiopericytoma. Author(s): Kruskal JB, Kane RA. Source: Journal of Ultrasound in Medicine : Official Journal of the American Institute of Ultrasound in Medicine. 2002 August; 21(8): 927-32. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12164579&dopt=Abstract
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Perception of hunger to insulin-induced hypoglycemia in anorexia nervosa. Author(s): Nakai Y, Koh T. Source: The International Journal of Eating Disorders. 2001 April; 29(3): 354-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11262517&dopt=Abstract
100 Hypoglycemia
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Persistent differences among centers over 3 years in glycemic control and hypoglycemia in a study of 3,805 children and adolescents with type 1 diabetes from the Hvidore Study Group. Author(s): Danne T, Mortensen HB, Hougaard P, Lynggaard H, Aanstoot HJ, Chiarelli F, Daneman D, Dorchy H, Garandeau P, Greene SA, Hoey H, Holl RW, Kaprio EA, Kocova M, Martul P, Matsuura N, Robertson KJ, Schoenle EJ, Sovik O, Swift PG, Tsou RM, Vanelli M, Aman J; For the Hvidore Study Group on Childhood Diabetes. Source: Diabetes Care. 2001 August; 24(8): 1342-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11473067&dopt=Abstract
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Persistent hyperinsulinemic hypoglycemia of infancy: experience at Siriraj Hospital. Author(s): Sawathiparnich P, Likitmaskul S, Angsusingha K, Nimkarn S, Chaichanwatanakul K, Laohapansang M, Tuchinda C. Source: J Med Assoc Thai. 2002 August; 85 Suppl 2: S506-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12403226&dopt=Abstract
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Persistent hyperinsulinemic hypoglycemia of infancy--successful therapy with nifedipine. Author(s): Shanbag P, Pathak A, Vaidya M, Shahid SK. Source: Indian J Pediatr. 2002 March; 69(3): 271-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12003307&dopt=Abstract
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Persistent severe hypoglycemia in acute zinc phosphide poisoning. Author(s): Frangides CY, Pneumatikos IA. Source: Intensive Care Medicine. 2002 February; 28(2): 223. Epub 2001 December 04. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11907673&dopt=Abstract
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Physical exercise-induced hyperinsulinemic hypoglycemia is an autosomal-dominant trait characterized by abnormal pyruvate-induced insulin release. Author(s): Otonkoski T, Kaminen N, Ustinov J, Lapatto R, Meissner T, Mayatepek E, Kere J, Sipila I. Source: Diabetes. 2003 January; 52(1): 199-204. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12502513&dopt=Abstract
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Possible gatifloxacin-induced hypoglycemia. Author(s): Baker SE, Hangii MC. Source: The Annals of Pharmacotherapy. 2002 November; 36(11): 1722-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12398567&dopt=Abstract
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Postprandial GLP-1, norepinephrine, and reactive hypoglycemia in dumping syndrome. Author(s): Gebhard B, Holst JJ, Biegelmayer C, Miholic J. Source: Digestive Diseases and Sciences. 2001 September; 46(9): 1915-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11575444&dopt=Abstract
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Postprandial reactive hypoglycemia. Author(s): Brun JF, Fedou C, Mercier J. Source: Diabetes & Metabolism. 2000 November; 26(5): 337-51. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11119013&dopt=Abstract
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Prevalence of hypoglycemia following pre-exercise carbohydrate ingestion is not accompanied By higher insulin sensitivity. Author(s): Jentjens RL, Jeukendrup AE. Source: International Journal of Sport Nutrition and Exercise Metabolism. 2002 December; 12(4): 398-413. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12500984&dopt=Abstract
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Preventive management of hypoglycemia in very low-birthweight infants following indomethacin therapy for patent ductus arteriosus. Author(s): Hosono S, Ohono T, Kimoto H, Nagoshi R, Shimizu M, Nozawa M. Source: Pediatrics International : Official Journal of the Japan Pediatric Society. 2001 October; 43(5): 465-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11737706&dopt=Abstract
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Primary malignant fibrous histiocytoma of the lung: IGF-II producing tumor induces fasting hypoglycemia. Author(s): Herrmann BL, Saller B, Kiess W, Morgenroth K, Drochner K, Schroder T, Mann K. Source: Experimental and Clinical Endocrinology & Diabetes : Official Journal, German Society of Endocrinology [and] German Diabetes Association. 2000; 108(8): 515-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11149628&dopt=Abstract
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Processed electroencephalographic changes associated with hypoglycemia during the resection of an insulinoma. Author(s): Hausman LM. Source: Anesthesiology. 2002 October; 97(4): 1013-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12357174&dopt=Abstract
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Profound hypoglycemia after intravasation of cystogram: A previously unreported complication of cystogram. Author(s): Nguyen ET, Komenaka IK, Gardezi S, Wise L. Source: Surgery. 2002 September; 132(3): 537. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12324777&dopt=Abstract
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Profound postoperative hypoglycemia in a malnourished patient. Author(s): Kurian J, Kaul V. Source: Canadian Journal of Anaesthesia = Journal Canadien D'anesthesie. 2001 October; 48(9): 881-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11606345&dopt=Abstract
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Progressive hypoglycemia's impact on driving simulation performance: occurrence, awareness, and correction. Author(s): Burden AC, Spiers N. Source: Diabetes Care. 2000 December; 23(12): 1866-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11128377&dopt=Abstract
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Prolonged hyperinsulinemic hypoglycemia in a small for date preterm. Author(s): Pezzati M, Barni S, Chiti G, Danesi G, Rubaltelli FF. Source: Minerva Pediatr. 2003 February; 55(1): 79-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12660630&dopt=Abstract
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Prospects for glycerol-rescued hypoglycemia as a cancer therapy. Author(s): McCarty MF. Source: Medical Hypotheses. 2001 March; 56(3): 286-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11359348&dopt=Abstract
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Protein-sensitive and fasting hypoglycemia in children with the hyperinsulinism/hyperammonemia syndrome. Author(s): Hsu BY, Kelly A, Thornton PS, Greenberg CR, Dilling LA, Stanley CA. Source: The Journal of Pediatrics. 2001 March; 138(3): 383-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11241047&dopt=Abstract
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PVN activation is suppressed by repeated hypoglycemia but not antecedent corticosterone in the rat. Author(s): Evans SB, Wilkinson CW, Bentson K, Gronbeck P, Zavosh A, Figlewicz DP. Source: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology. 2001 November; 281(5): R1426-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11641112&dopt=Abstract
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Rate and risk factors of hypoglycemia in large-for-gestational-age newborn infants of nondiabetic mothers. Author(s): Schaefer-Graf UM, Rossi R, Buhrer C, Siebert G, Kjos SL, Dudenhausen JW, Vetter K. Source: American Journal of Obstetrics and Gynecology. 2002 October; 187(4): 913-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12388976&dopt=Abstract
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Renal compensation for impaired hepatic glucose release during hypoglycemia in type 2 diabetes: further evidence for hepatorenal reciprocity. Author(s): Woerle HJ, Meyer C, Popa EM, Cryer PE, Gerich JE. Source: Diabetes. 2003 June; 52(6): 1386-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12765948&dopt=Abstract
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Repaglinide-induced factitious hypoglycemia. Author(s): Hirshberg B, Skarulis MC, Pucino F, Csako G, Brennan R, Gorden P. Source: The Journal of Clinical Endocrinology and Metabolism. 2001 February; 86(2): 475-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11157993&dopt=Abstract
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Repeated hypoglycemia and cognitive decline. A case report. Author(s): Akyol A, Kiylioglu N, Bolukbasi O, Guney E, Yurekli Y. Source: Neuroendocrinol Lett. 2003 February-April; 24(1-2): 54-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12743533&dopt=Abstract
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Reproduction of features of the glucagonoma syndrome with continuous intravenous glucagon infusion as therapy for tumor-induced hypoglycemia. Author(s): Case CC, Vassilopoulou-Sellin R. Source: Endocrine Practice : Official Journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists. 2003 January-February; 9(1): 22-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12917088&dopt=Abstract
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Risk factors for frequent and severe hypoglycemia in type 1 diabetes. Author(s): Allen C, LeCaire T, Palta M, Daniels K, Meredith M, D'Alessio DJ; Wisconsin Diabetes Registry Project. Source: Diabetes Care. 2001 November; 24(11): 1878-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11679450&dopt=Abstract
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Risk indicators predictive for severe hypoglycemia during the first trimester of type 1 diabetic pregnancy. Author(s): Evers IM, ter Braak EW, de Valk HW, van Der Schoot B, Janssen N, Visser GH. Source: Diabetes Care. 2002 March; 25(3): 554-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11874946&dopt=Abstract
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Risky delay of hypoglycemia detection by glucose monitoring at the arm. Author(s): Jungheim K, Koschinsky T. Source: Diabetes Care. 2001 July; 24(7): 1303-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11423524&dopt=Abstract
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Screening for hypoglycemia in healthy term neonates: effects on breastfeeding. Author(s): Haninger NC, Farley CL. Source: Journal of Midwifery & Women's Health. 2001 September-October; 46(5): 292301. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11725900&dopt=Abstract
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Self-treatment of hypoglycemia while driving. Author(s): Cox DJ, Gonder-Frederick LA, Kovatchev BP, Clarke WL. Source: Diabetes Research and Clinical Practice. 2001 October; 54(1): 17-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11532326&dopt=Abstract
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Sequential hypoglycemia, hyperglycemia, and the carcinoid syndrome arising from a plurihormonal neuroendocrine neoplasm. Author(s): Mitzner LD, Nohria A, Chacho M, Inzucchi SE. Source: Endocrine Practice : Official Journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists. 2000 September-October; 6(5): 370-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11141588&dopt=Abstract
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Serious hypoglycemia: Munchausen's syndrome? Author(s): Trenque T, Hoizey G, Lamiable D. Source: Diabetes Care. 2001 April; 24(4): 792-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11315856&dopt=Abstract
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Sertraline-induced hypoglycemia. Author(s): Pollak PT, Mukherjee SD, Fraser AD. Source: The Annals of Pharmacotherapy. 2001 November; 35(11): 1371-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11724085&dopt=Abstract
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Serum ACE predicts severe hypoglycemia in children and adolescents with type 1 diabetes. Author(s): Nordfeldt S, Samuelsson U. Source: Diabetes Care. 2003 February; 26(2): 274-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12547848&dopt=Abstract
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Severe and persistent hypoglycemia due to gatifloxacin interaction with oral hypoglycemic agents. Author(s): Menzies DJ, Dorsainvil PA, Cunha BA, Johnson DH. Source: The American Journal of Medicine. 2002 August 15; 113(3): 232-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12208383&dopt=Abstract
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Severe and prolonged hypoglycemia triggered by long-acting octreotide in a patient with malignant mesenchymal tumor: case report. Author(s): Sari R, Altunbas H, Ozdogan M, Gurer EI, Karayalcin U. Source: Journal of Chemotherapy (Florence, Italy). 2003 February; 15(1): 85-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12678421&dopt=Abstract
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Severe hypoglycemia and long-term spatial memory in children with type 1 diabetes mellitus: a retrospective study. Author(s): Hershey T, Lillie R, Sadler M, White NH. Source: Journal of the International Neuropsychological Society : Jins. 2003 July; 9(5): 740-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12901780&dopt=Abstract
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Severe hypoglycemia due to insulin autoimmune syndrome with insulin autoantibodies crossreactive to proinsulin. Author(s): Lohmann T, Kratzsch J, Kellner K, Witzigmann H, Hauss J, Paschke R. Source: Experimental and Clinical Endocrinology & Diabetes : Official Journal, German Society of Endocrinology [and] German Diabetes Association. 2001; 109(4): 245-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11453038&dopt=Abstract
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Severe hypoglycemia from clarithromycin-sulfonylurea drug interaction. Author(s): Bussing R, Gende A. Source: Diabetes Care. 2002 September; 25(9): 1659-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12196446&dopt=Abstract
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Severe hypoglycemia in a patient with acute renal failure due to tumor lysis syndrome. Author(s): Shnaider A, Basok A, Rogachev B, Tovbin D, Mostoslavsky M. Source: Isr Med Assoc J. 2002 September; 4(9): 730-1. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12440245&dopt=Abstract
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Severe hypoglycemia in an elderly patient treated with metformin. Author(s): Zitzmann S, Reimann IR, Schmechel H. Source: Int J Clin Pharmacol Ther. 2002 March; 40(3): 108-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11911598&dopt=Abstract
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Sexual dimorphism in counterregulatory responses to hypoglycemia after antecedent exercise. Author(s): Galassetti P, Neill AR, Tate D, Ertl AC, Wasserman DH, Davis SN. Source: The Journal of Clinical Endocrinology and Metabolism. 2001 August; 86(8): 3516-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11502773&dopt=Abstract
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Short-term, delayed, and working memory are impaired during hypoglycemia in individuals with type 1 diabetes. Author(s): Sommerfield AJ, Deary IJ, McAulay V, Frier BM. Source: Diabetes Care. 2003 February; 26(2): 390-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12547868&dopt=Abstract
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Sion Hospital formulae for management of hypoglycemia. Author(s): Mathai SS, Mondkar JA. Source: Indian Pediatrics. 2001 August; 38(8): 928-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11521012&dopt=Abstract
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Sleep-related hypoglycemia-associated autonomic failure in type 1 diabetes: reduced awakening from sleep during hypoglycemia. Author(s): Banarer S, Cryer PE. Source: Diabetes. 2003 May; 52(5): 1195-203. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12716752&dopt=Abstract
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Somatotropic, lactotropic and adrenocortical responses to insulin-induced hypoglycemia in patients with rheumatoid arthritis. Author(s): Rovensky J, Bakosova J, Koska J, Ksinantova L, Jezova D, Vigas M. Source: Annals of the New York Academy of Sciences. 2002 June; 966: 263-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12114282&dopt=Abstract
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Spontaneous hypoglycemia in childhood is accompanied by paradoxically low serum growth hormone and appropriate cortisol counterregulatory hormonal responses. Author(s): Hussain K, Hindmarsh P, Aynsley-Green A. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 August; 88(8): 3715-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12915660&dopt=Abstract
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Spurious reporting of nocturnal hypoglycemia by CGMS in patients with tightly controlled type 1 diabetes. Author(s): McGowan K, Thomas W, Moran A. Source: Diabetes Care. 2002 September; 25(9): 1499-503. Erratum In: Diabetes Care. 2003 February; 26(2): 553. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12196417&dopt=Abstract
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Streptococcal toxic shock syndrome presenting with spontaneous hypoglycemia in a chronic hemodialysis patient: pathophysiological mechanisms. Author(s): Igaki N, Matsuda T, Hirota Y, Kawaguchi T, Tamada F, Goto T. Source: Intern Med. 2003 May; 42(5): 421-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12793713&dopt=Abstract
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Striking differences in glucose and lactate levels between brain extracellular fluid and plasma in conscious human subjects: effects of hyperglycemia and hypoglycemia. Author(s): Abi-Saab WM, Maggs DG, Jones T, Jacob R, Srihari V, Thompson J, Kerr D, Leone P, Krystal JH, Spencer DD, During MJ, Sherwin RS. Source: Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism. 2002 March; 22(3): 271-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11891432&dopt=Abstract
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Subcutaneous glucagon may be better than oral glucose for prehospital treatment of symptomatic hypoglycemia. Author(s): Vermeulen MJ, Klompas M, Ray JG, Mazza C, Morrison LJ. Source: Diabetes Care. 2003 August; 26(8): 2472-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12882885&dopt=Abstract
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Sustained hypoglycemia affects glucose transporter expression of human blood leukocytes. Author(s): Korgun ET, Demir R, Sedlmayr P, Desoye G, Arikan GM, Puerstner P, Haeusler M, Dohr G, Skofitsch G, Hahn T. Source: Blood Cells, Molecules & Diseases. 2002 March-April; 28(2): 152-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12064911&dopt=Abstract
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Symptomatic hypoglycemia in children receiving oral purine analogues for treatment of childhood acute lymphoblastic leukemia. Author(s): Ziino O, Russo D, Orlando MA, Benigno V, Locatelli F, Arico M. Source: Medical and Pediatric Oncology. 2002 July; 39(1): 32-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12116076&dopt=Abstract
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Systemic and local adrenergic regulation of muscle glucose utilization during hypoglycemia in healthy subjects. Author(s): Hoffman RP, Sinkey CA, Dopp JM, Phillips BG. Source: Diabetes. 2002 March; 51(3): 734-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11872674&dopt=Abstract
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Telemedical care reduces hypoglycemias and improves glycemic control in children and adolescents with type 1 diabetes. Author(s): Liesenfeld B, Renner R, Neese M, Hepp KD. Source: Diabetes Technology & Therapeutics. 2000 Winter; 2(4): 561-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11469619&dopt=Abstract
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The association of leukocyte adhesion defect type I and persistent hyperinsulinemic hypoglycemia of infancy in a Saudi Arabian family. Author(s): Suliaman F, Jabbar MA. Source: Pediatric Hematology and Oncology. 2002 September; 19(6): 429-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12186366&dopt=Abstract
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The best defense against hypoglycemia is to recognize it: is caffeine useful? Author(s): Watson J, Kerr D. Source: Diabetes Technology & Therapeutics. 1999 Summer; 1(2): 193-200. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11475292&dopt=Abstract
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The continuous glucose monitoring system is useful for detecting unrecognized hypoglycemias in patients with type 1 and type 2 diabetes but is not better than frequent capillary glucose measurements for improving metabolic control. Author(s): Chico A, Vidal-Rios P, Subira M, Novials A. Source: Diabetes Care. 2003 April; 26(4): 1153-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12663589&dopt=Abstract
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The diagnosis of fasting hypoglycemia due to an islet-cell tumor obscured by a highly specific insulin assay. Author(s): Chia CW, Saudek CD. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 April; 88(4): 1464-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12679423&dopt=Abstract
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The economic effect of hypoglycemia in a health plan. Author(s): Heaton A, Martin S, Brelje T. Source: Manag Care Interface. 2003 July; 16(7): 23-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12908214&dopt=Abstract
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The effect of acute hypoglycemia on brain function and activation: a functional magnetic resonance imaging study. Author(s): Rosenthal JM, Amiel SA, Yaguez L, Bullmore E, Hopkins D, Evans M, Pernet A, Reid H, Giampietro V, Andrew CM, Suckling J, Simmons A, Williams SC. Source: Diabetes. 2001 July; 50(7): 1618-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11423484&dopt=Abstract
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The focal form of persistent hyperinsulinemic hypoglycemia of infancy. Author(s): Sempoux C, Guiot Y, Rahier J. Source: Diabetes. 2001 February; 50 Suppl 1: S182-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11272187&dopt=Abstract
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The focal form of persistent hyperinsulinemic hypoglycemia of infancy: morphological and molecular studies show structural and functional differences with insulinoma. Author(s): Sempoux C, Guiot Y, Dahan K, Moulin P, Stevens M, Lambot V, de Lonlay P, Fournet JC, Junien C, Jaubert F, Nihoul-Fekete C, Saudubray JM, Rahier J. Source: Diabetes. 2003 March; 52(3): 784-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12606521&dopt=Abstract
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The impact of severe hypoglycemia and impaired awareness of hypoglycemia on relatives of patients with type 1 diabetes. Author(s): Jorgensen HV, Pedersen-Bjergaard U, Rasmussen AK, Borch-Johnsen K. Source: Diabetes Care. 2003 April; 26(4): 1106-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12663581&dopt=Abstract
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The impact of the diabetes control and complications trial and humalog insulin on glycohemoglobin levels and severe hypoglycemia in type 1 diabetes. Author(s): Chase HP, Lockspeiser T, Peery B, Shepherd M, MacKenzie T, Anderson J, Garg SK. Source: Diabetes Care. 2001 March; 24(3): 430-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11289463&dopt=Abstract
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The insulin hypoglycemia test: hypoglycemic criteria and reproducibility. Author(s): Nye EJ, Grice JE, Hockings GI, Strakosch CR, Crosbie GV, Walters MM, Torpy DJ, Jackson RV. Source: Journal of Neuroendocrinology. 2001 June; 13(6): 524-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11412339&dopt=Abstract
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The need for hypoglycemia detection and prevention in type 1 diabetes. Author(s): Klonoff DC. Source: Diabetes Technology & Therapeutics. 2001 Winter; 3(4): 567-70. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11911168&dopt=Abstract
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The role of prandial glucose regulation with repaglinide in addressing the problem of hypoglycemia in the treatment of type 2 diabetes. Author(s): Owens D. Source: J Assoc Physicians India. 2001 January 25; 49: 54-61. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11235607&dopt=Abstract
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The sulfonylurea glyburide induces impairment of glucagon and growth hormone responses during mild insulin-induced hypoglycemia. Author(s): ter Braak EW, Appelman AM, van der Tweel I, Erkelens DW, van Haeften TW. Source: Diabetes Care. 2002 January; 25(1): 107-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11772910&dopt=Abstract
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Theophylline improves hypoglycemia unawareness in type 1 diabetes. Author(s): de Galan BE, Tack CJ, Lenders JW, Pasman JW, Elving LD, Russel FG, Lutterman JA, Smits P. Source: Diabetes. 2002 March; 51(3): 790-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11872681&dopt=Abstract
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Timely detection of hypoglycemia by monitoring blood glucose levels of samples obtained from the palm of the hand. Author(s): Peled N, Gwalani SL. Source: Diabetes Technology & Therapeutics. 2002; 4(1): 83-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12017425&dopt=Abstract
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Tissue-specific deletion of Foxa2 in pancreatic beta cells results in hyperinsulinemic hypoglycemia. Author(s): Sund NJ, Vatamaniuk MZ, Casey M, Ang SL, Magnuson MA, Stoffers DA, Matschinsky FM, Kaestner KH. Source: Genes & Development. 2001 July 1; 15(13): 1706-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11445544&dopt=Abstract
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Transient hyperinsulinism in an asphyxiated newborn infant with hypoglycemia. Author(s): Clark W, O'Donovan D. Source: American Journal of Perinatology. 2001 June; 18(4): 175-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11444360&dopt=Abstract
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Transient neonatal hypoglycemia: cranial US and MRI findings. Author(s): Cakmakci H, Usal C, Karabay N, Kovanlikaya A. Source: European Radiology. 2001; 11(12): 2585-8. Epub 2001 January 25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11734963&dopt=Abstract
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Transient neonatal hypoglycemia--long-term effects on neurodevelopmental outcome. Author(s): Ann Intern Med. 2002 Apr 2;136(7):I29 Source: J Pediatr Endocrinol Metab. 2002 March; 15(3): 319-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11926807
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Troglitazone amplifies counterregulatory responses to hypoglycemia in nondiabetic subjects. Author(s): Gabriely I, Wozniak R, Hawkins M, Shamoon H. Source: The Journal of Clinical Endocrinology and Metabolism. 2001 February; 86(2): 521-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11158003&dopt=Abstract
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Tumor-associated hypoglycemia from metastatic colorectal adenocarcinoma: case report and review of the literature. Author(s): Ko AH, Bergsland EK, Lee GA. Source: Digestive Diseases and Sciences. 2003 January; 48(1): 192-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12645810&dopt=Abstract
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Two cases of large solitary fibrous tumors of the pleura associated with fasting hypoglycemia. Author(s): Kim JH, Kim JO, Kim SY, Na MH, Lim SP, Kim JM. Source: European Radiology. 2001; 11(5): 819-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11372615&dopt=Abstract
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Unexpected hypoglycemia in a critically ill patient. Author(s): Bates DW. Source: Annals of Internal Medicine. 2002 July 16; 137(2): 110-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12118966&dopt=Abstract
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Unilateral cortical necrosis following status epilepticus with hypoglycemia. Author(s): Christiaens FJ, Mewasingh LD, Christophe C, Goldman S, Dan B. Source: Brain & Development. 2003 March; 25(2): 107-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12581806&dopt=Abstract
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Use of octreotide to treat prolonged sulfonylurea-induced hypoglycemia in a patient with chronic renal failure. Author(s): Nzerue CM, Thomas J, Volcy J, Edeki T. Source: Int J Artif Organs. 2003 January; 26(1): 86-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12602474&dopt=Abstract
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Vascular endothelial growth factor: a novel endocrine defensive response to hypoglycemia. Author(s): Dantz D, Bewersdorf J, Fruehwald-Schultes B, Kern W, Jelkmann W, Born J, Fehm HL, Peters A. Source: The Journal of Clinical Endocrinology and Metabolism. 2002 February; 87(2): 835-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11836329&dopt=Abstract
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When it is more than transient neonatal hypoglycemia: hyperinsulinemia--a case study challenge. Author(s): Shirland L. Source: Neonatal Netw. 2001 June; 20(4): 5-11. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12143902&dopt=Abstract
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Which threshold to detect hypoglycemia? Value of receiver-operator curve analysis to find a compromise between sensitivity and specificity. Author(s): Reach G. Source: Diabetes Care. 2001 May; 24(5): 803-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11347733&dopt=Abstract
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CHAPTER 2. NUTRITION AND HYPOGLYCEMIA Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and hypoglycemia.
Finding Nutrition Studies on Hypoglycemia 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 “hypoglycemia” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.
7 Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.
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The following information is typical of that found when using the “Full IBIDS Database” to search for “hypoglycemia” (or a synonym): •
Atomic absorption spectrophotometric analysis of the hypoglycemic trace elements of Ivy (Hedera helix L.) leaves. Author(s): Peshawar Univ. (Pakistan). Dept. of Pharmacy Source: Ibrar, M. Hamdard-Medicus (Pakistan). (Jul-Sept 2000). volume 43(3) page 68-71.
Additional physician-oriented references include: •
Adrenal crisis presenting as hypoglycemic coma. Author(s): Department of Intensive Care, Children's Hospital, University of Zurich, Steinwiesstrasse 75, CH-8032 Zurich, Swizerland.
[email protected] Source: Fischer, J E Stallmach, T Fanconi, S Intensive-Care-Med. 2000 January; 26(1): 1058 0342-4642
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Arginine vasopressin response to insulin-induced hypoglycemia in insulindependent diabetics with asymptomatic hypoglycemia. Source: Wolf, J.P. Massol, J. Nguyen, N.U. Berthelay, S. Horm-Metab-Res-HormStoffwechselforschung-Horm-Metab. Stuttgart, W. Ger. : Georg Thieme. April 1990. volume 22 (4) page 232-236. 0018-5043
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Characterization of the hypoglycemic effects of Trigonella foenum graecum seed. Source: Ali, L. Khan, A.K.A. Hassan, Z. Mosihuzzaman, M. Nahar, N. Nasreen, T. Nur e Alam, M. Rokeya, B. Planta-med. Stuttgart : Georg Thieme Verlag,. August 1995. volume 61 (4) page 358-360. 0032-0943
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Effect of bio-adhesive polymers, sodium salicylate, polyoxyethylene-9-lauryl ether and method of preparation on the relative hypoglycemia produced by insulin enteric coated capsules in diabetic beagle dogs. Author(s): Department of Pharmaceutics, College of Pharmacy, King Saud University, Saudi Arabia. Source: Hosny, E A al Shora, H I el mazar, M M A Boll-Chim-Farm. 2002 Jan-February; 141(1): 67-74 0006-6648
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Effect of growth hormone treatment on hypoglycemia in a patient with both hepatic glycogen synthase and isolated growth hormone deficiencies. Author(s): Gottfried v. Preyer'sches Kinderspital, Vienna, Austria.
[email protected] Source: Blumel, P Mullis, P E J-Pediatr-Endocrinol-Metab. 2001 Sep-October; 14(8): 11515
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Effect of some hypoglycemic herbs on the activity of phase I and II drugmetabolizing enzymes in alloxan-induced diabetic rats. Author(s): Department of Bioscience and Technology, Institute of Graduate Studies and Research, Alexandria University, Egypt.
[email protected] Source: Sheweita, S A Newairy, A A Mansour, H A Yousef, M I Toxicology. 2002 May 24; 174(2): 131-9 0300-483X
•
Glut-1 expression and its response to hypoglycemia in the embryonic mouse heart. Author(s): Department of Anatomy, Physiological Sciences, and Radiology, North Carolina State University College of Veterinary Medicine, Raleigh 27606, USA.
[email protected] Source: Smoak, I W Branch, S Anat-Embryol-(Berl). 2000 May; 201(5): 327-33 0340-2061
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Glutamate dependence of GABA levels in neurons of hypoxic and hypoglycemic rat hippocampal slices. Author(s): Department of Anatomy and Neurobiology, Colorado State University, Fort Collins, CO 80523, USA.
[email protected] Source: Madl, J E Royer, S M Neuroscience. 2000; 96(4): 657-64 0306-4522
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Hypoglycemia effect of Acrocomia mexicana Karw. Source: Perez G, S. Perez G, R.M. Perez G, C. Vargas S, R. Phyton. Buenos Aires : Fundacion Romulo Raggio. 1991. volume 53 (1) page 39-42. 0031-9457
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Hypoglycemic and antihyperglycemic activity of Syzygium alternifolium (Wt.) Walp. seed extracts in normal and diabetic rats. Source: Kameswara Rao, B. Appa Rao, C. Phytomedicine. Stuttgart; New York : G. Fischer, c1994-. March 2001. volume 8 (2) page 88-93. 0944-7113
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Laparoscopic pancreatectomy for persistent hyperinsulinemic hypoglycemia of infancy. Author(s): Section of Pediatric Surgery, University of Tennessee, 777 Washington Avenue, Ste. P220, Memphis, TN 38105, USA. Source: Blakely, M L Lobe, T E Cohen, J Burghen, G A Surg-Endosc. 2001 August; 15(8): 897-8 1432-2218
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Melatonin inhibits oxytocin response to insulin-induced hypoglycemia, but not to angiotensin II in normal men. Author(s): Department of Internal Medicine, School of Medicine, University of Parma, Italy. Source: Chiodera, P Volpi, R Capretti, L Giuliani, N Caffarri, G Coiro, V J-NeuralTransm. 1998; 105(2-3): 173-80
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Neonatal glucose metabolism: differential diagnoses, evaluation, and treatment of hypoglycemia. Author(s): Neonatal Intensive Care Unit, Central DuPage Hospital, Chicago, USA.
[email protected] Source: Cowett, Richard M Loughead, Jeffrey L Neonatal-Netw. 2002 June; 21(4): 9-19 0730-0832
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Prevalence of hypoglycemia following pre-exercise carbohydrate ingestion is not accompanied By higher insulin sensitivity. Author(s): Human Performance Laboratory, School of Sport and Exercise Sciences, University of Birmingham, Edgbaston, B15 2TT, Birmingham, UK. Source: Jentjens, R L Jeukendrup, A E Int-J-Sport-Nutr-Exerc-Metab. 2002 December; 12(4): 398-413 1526-484X
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Preventing hypoglycemia (low blood glucose) in children. Source: Kaufman, F. Diabetes-forecast. Alexandria, Va. : American Diabetes Association Inc. June 1999. volume 52 (6) page 77-79. 0095-8301
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Preventive management of hypoglycemia in very low-birthweight infants following indomethacin therapy for patent ductus arteriosus. Author(s): Division of Neonatology, Saitama Children's Medical Center, Saitama, Japan.
[email protected] Source: Hosono, S Ohono, T Kimoto, H Nagoshi, R Shimizu, M Nozawa, M Pediatr-Int. 2001 October; 43(5): 465-8 1328-8067
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Relative hypoglycemic effect of insulin suppositories in diabetic beagle dogs: optimization of various concentrations of sodium salicylate and polyoxyethylene-9lauryl ether. Author(s): Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
[email protected] Source: Hosny, E A Al Shora, H I Elmazar, M M Biol-Pharm-Bull. 2001 November; 24(11): 1294-7 0918-6158
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Screening for hypoglycemia in healthy term neonates: effects on breastfeeding. Author(s): Greene Memorial Hospital in Xenia, Ohio, USA. Source: Haninger, N C Farley, C L J-Midwifery-Womens-Health. 2001 Sep-October; 46(5): 292-301 1526-9523
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Sequential hypoglycemia, hyperglycemia, and the carcinoid syndrome arising from a plurihormonal neuroendocrine neoplasm. Author(s): Department of Medicine, Yale University School of Medicine, New Haven, Connecticut 06520, USA. Source: Mitzner, L D Nohria, A Chacho, M Inzucchi, S E Endocr-Pract. 2000 SepOctober; 6(5): 370-4 1530-891X
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Severe hypoglycemia in Spanish diabetic children and adolescents. Study Group of Infantile Diabetes of the Spanish Paediatric Endocrinology Society. Author(s): Valencia and Valladolid University Clinic Hospitals, Spain. Source: Lopez, M J Oyarzabal, M Rodriguez, M Barrio, R Hermoso, F Blasco, L J-PediatrEndocrinol-Metab. 1999 Jan-February; 12(1): 85-7
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Studies on the mechanism of the hypoglycemic activity of ginsenoside-Rb2 in streptozotocin-diabetic rats. Source: Yokozawa, T. Kobayashi, T. Oura, H. Kawashima, Y. Chem-Pharm-Bull. Tokyo : Pharmaceutical Society of Japan. February 1985. volume 33 (2) page 869-872. 0009-2363
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The effect of chromium supplementation on the glucose tolerance of hypoglycemic, marginally hyperglycemic and normal subjects. Source: Anderson, R.A. Polansky, M.M. Bryden, N.A. Kozlovsky, A.S. Trace elements in man and animals : TEMA 5 : proceedings of the fifth International Symposium on Trace Elements in Man and Animals / editors C.F. Mills, I. Bremner, & J.K. Chesters. Farnham Royal, Slough : Commonwealth Agricultural Bureaux, c1985. page 811-814. ISBN: 085198553X
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Transport refusal by hypoglycemic patients after on-scene intravenous dextrose. Author(s): University of Western Ontario Faculty of Medicine, London, ON, Canada.
[email protected] Source: Carter, A J Keane, P S Dreyer, J F Acad-Emerg-Med. 2002 August; 9(8): 855-7 1069-6563
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Treatment of alimentary and reactive hypoglycemia. Source: Lefebvre, P.J. Hypoglycemia / editors, D. Andreani, Volume Marks, P.J. Lefebvre. New York : Raven Press, c1987. page 63-69. charts. ISBN: 0881673218
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When it is more than transient neonatal hypoglycemia: hyperinsulinemia--a case study challenge. Author(s): Neonatal Advanced Practice Service, Cape Fear Valley Health Care System, Fayetteville, North Carolina 28302-2000, USA.
[email protected] Source: Shirland, L Neonatal-Netw. 2001 June; 20(4): 5-11 0730-0832
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Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: •
healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0
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The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov
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The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov
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The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/
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The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/
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Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/
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Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/
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Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/
Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: •
AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats
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Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html
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Google: http://directory.google.com/Top/Health/Nutrition/
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Healthnotes: http://www.healthnotes.com/
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Open Directory Project: http://dmoz.org/Health/Nutrition/
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Yahoo.com: http://dir.yahoo.com/Health/Nutrition/
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WebMD®Health: http://my.webmd.com/nutrition
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
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The following is a specific Web list relating to hypoglycemia; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •
Vitamins Vitamin B3 Source: Healthnotes, Inc.; www.healthnotes.com Vitamin B6 Source: Healthnotes, Inc.; www.healthnotes.com Vitamin C Source: Healthnotes, Inc.; www.healthnotes.com Vitamin E Source: Healthnotes, Inc.; www.healthnotes.com
•
Minerals Chromium Source: Healthnotes, Inc.; www.healthnotes.com Chromium Source: Integrative Medicine Communications; www.drkoop.com Chromium Source: Prima Communications, Inc.www.personalhealthzone.com Chromium Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10018,00.html Copper Source: Healthnotes, Inc.; www.healthnotes.com Magnesium Source: Healthnotes, Inc.; www.healthnotes.com Magnesium Source: Prima Communications, Inc.www.personalhealthzone.com Manganese Source: Healthnotes, Inc.; www.healthnotes.com Sulfur Source: Integrative Medicine Communications; www.drkoop.com
Nutrition
Vanadium Alternative names: Vanadate, Vanadyl Source: Integrative Medicine Communications; www.drkoop.com Zinc Source: Healthnotes, Inc.; www.healthnotes.com •
Food and Diet Burdock Alternative names: Arctium lappa, Arctium minus, Arctium tomentosum Source: Integrative Medicine Communications; www.drkoop.com Burdock Source: Prima Communications, Inc.www.personalhealthzone.com Burdock Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,235,00.html Coffee Source: Healthnotes, Inc.; www.healthnotes.com Fasting Diet Source: Healthnotes, Inc.; www.healthnotes.com Hypoglycemia Source: Healthnotes, Inc.; www.healthnotes.com Special Diets Index Source: Healthnotes, Inc.; www.healthnotes.com Tea Source: Healthnotes, Inc.; www.healthnotes.com
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CHAPTER 3. HYPOGLYCEMIA
ALTERNATIVE
MEDICINE
AND
Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to hypoglycemia. 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 hypoglycemia 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 “hypoglycemia” (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 hypoglycemia: •
“Hypoglycemic” anxiety. The role of reinforcement in psychophysiological disorders. Author(s): Klonoff EA, Biglan A. Source: Behavior Modification. 1987 January; 11(1): 102-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3334118&dopt=Abstract
•
A comparison of leucine- and acetoacetate-induced hypoglycemia in man. Author(s): FAJANS SS, FLOYD JC Jr, KNOPF RF, CONN JW. Source: The Journal of Clinical Investigation. 1964 October; 43: 2003-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14236224&dopt=Abstract
•
A preliminary study of the hypoglycemic action of heartwood of Pterocarpus marsupium roxb. Author(s): Shah DS.
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Source: The Indian Journal of Medical Research. 1967 February; 55(2): 166-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6045054&dopt=Abstract •
A specific inhibitor of calcium/calmodulin-dependent protein kinase-II provides neuroprotection against NMDA- and hypoxia/hypoglycemia-induced cell death. Author(s): Hajimohammadreza I, Probert AW, Coughenour LL, Borosky SA, Marcoux FW, Boxer PA, Wang KK. Source: The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. 1995 May; 15(5 Pt 2): 4093-101. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7538570&dopt=Abstract
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Alcohol-induced hypoglycemia and coma caused by alcohol sponging. Author(s): Moss MH. Source: Pediatrics. 1970 September; 46(3): 445-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5454799&dopt=Abstract
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Anti-inflammatory and neuroprotective effects of magnolol in chemical hypoxia in rat cultured cortical cells in hypoglycemic media. Author(s): Lee MM, Huang HM, Hsieh MT, Chen CS, Yeh FT, Kuo JS. Source: Chin J Physiol. 2000 June 30; 43(2): 61-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10994695&dopt=Abstract
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Changes in BAEP under hypoglycemia: temperature-related? Author(s): Durrant JD, Gerich JE, Mitrakou A, Jenssen T, Hyre RJ. Source: Electroencephalography and Clinical Neurophysiology. 1991 NovemberDecember; 80(6): 547-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1720731&dopt=Abstract
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Drug-induced hypoglycemia. A review based on 473 cases. Author(s): Seltzer HS. Source: Diabetes. 1972 September; 21(9): 955-66. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4626706&dopt=Abstract
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Effect of dietary fiber on complications of gastric surgery: prevention of postprandial hypoglycemia by pectin. Author(s): Jenkins DJ, Gassull MA, Leeds AR, Metz G, Dilawari JB, Slavin B, Blendis LM. Source: Gastroenterology. 1977 August; 73(2): 215-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=873118&dopt=Abstract
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Effect of dietary niacin supplementation on phlorhizin and 1,3-butanediol-induced ketonemia and hypoglycemia in steers. Author(s): Dufva GS, Bartley EE, Nagaraja TG, Dayton AD, Frey RA.
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Source: Am J Vet Res. 1984 September; 45(9): 1835-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6497141&dopt=Abstract •
Effect of hypoglycemia induced by insulin on the depth EEG in the chicken. Author(s): Shimada K. Source: General and Comparative Endocrinology. 1974 June; 23(2): 136-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4600541&dopt=Abstract
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Effect of insulin hypoglycemia on the blood adrenaline level and on the 24-hour urinary excretion rate of 17-hydroxysteroids (17-ohs) in patients with bronchial asthma, treated in Szczawano-spa. Author(s): Kleczenski A, Chachaj W, Suchnicka R, Wrzyszcz M. Source: Pol Med J. 1967; 6(5): 1136-42. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6080876&dopt=Abstract
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Effect of some hypoglycemic herbs on the activity of phase I and II drugmetabolizing enzymes in alloxan-induced diabetic rats. Author(s): Sheweita SA, Newairy AA, Mansour HA, Yousef MI. Source: Toxicology. 2002 May 24; 174(2): 131-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11985890&dopt=Abstract
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Effect of structured group education on glycemic control and hypoglycemia in insulin-treated patients. Author(s): Koev DJ, Tankova TI, Kozlovski PG. Source: Diabetes Care. 2003 January; 26(1): 251. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12502698&dopt=Abstract
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Effects of bilobalide on hypoxia/hypoglycemia-stimulated glutamate efflux from rat cortical brain slices. Author(s): Johns L, Sinclair AJ, Davies JA. Source: Neurochemical Research. 2002 May; 27(5): 369-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12064351&dopt=Abstract
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Functional hypoglycemia: implications for occupational health nurses. Author(s): Edwards R, Wells BJ. Source: Occup Health Nurs. 1985 April; 33(4): 174-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3885110&dopt=Abstract
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Hypoglycemia due to folk medicine. Author(s): Baba T, Kataoka K, Itakura M.
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Source: Diabetes Care. 1999 August; 22(8): 1376. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10480789&dopt=Abstract •
Hypoglycemia treatment. Author(s): Slover-Zipf J. Source: The American Journal of Nursing. 1999 October; 99(10): 14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10542837&dopt=Abstract
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Hypoglycemia: a controversial illness in U.S. society. Author(s): Singer M, Arnold C, Fitzgerald M, Madden L, von Legat CV. Source: Medical Anthropology. 1984 Winter; 8(1): 1-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6536847&dopt=Abstract
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Hypoglycemic action of embelia madagascariensis in normal and diabetic mice. Author(s): Miura T, Kato A. Source: The American Journal of Chinese Medicine. 1997; 25(2): 169-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9288363&dopt=Abstract
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Hypoglycemic activity of Neurolaena lobata (L.) R. BR. Author(s): Gupta MP, Solis NG, Avella ME, Sanchez C. Source: Journal of Ethnopharmacology. 1984 May; 10(3): 323-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6748709&dopt=Abstract
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Hypoglycemic activity of Salvia fruticosa Mill. from Cyprus. Author(s): Perfumi M, Arnold N, Tacconi R. Source: Journal of Ethnopharmacology. 1991 September; 34(2-3): 135-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1795516&dopt=Abstract
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Hypoglycemic and antihyperglycemic effect of Brassicajuncea diet and their effect on hepatic glycogen content and the key enzymes of carbohydrate metabolism. Author(s): Grover JK, Yadav S, Vats V. Source: Molecular and Cellular Biochemistry. 2002 December; 241(1-2): 95-101. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12482030&dopt=Abstract
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Hypoglycemic constituents of Panax ginseng. Author(s): Ng TB, Yeung HW. Source: General Pharmacology. 1985; 16(6): 549-52. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3910515&dopt=Abstract
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Hypoglycemic effect of the water extract of Piper sarmentosum in rats. Author(s): Peungvicha P, Thirawarapan SS, Temsiririrkkul R, Watanabe H, Kumar Prasain J, Kadota S.
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Source: Journal of Ethnopharmacology. 1998 February; 60(1): 27-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9533429&dopt=Abstract •
Hypoglycemic effect of water extract of the root of Pandanus odorus RIDL. Author(s): Peungvicha P, Thirawarapan SS, Watanabe H. Source: Biological & Pharmaceutical Bulletin. 1996 March; 19(3): 364-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8924901&dopt=Abstract
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Hypoglycemic effects of leucodelphinidin derivative isolated from Ficus bengalensis (Linn). Author(s): Geetha BS, Mathew BC, Augusti KT. Source: Indian J Physiol Pharmacol. 1994 July; 38(3): 220-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7814088&dopt=Abstract
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Hypoglycemic injury to the immature brain. Author(s): Yager JY. Source: Clin Perinatol. 2002 December; 29(4): 651-74, Vi. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12516740&dopt=Abstract
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Identification of 3-hydroxy-3-methylglutaric acid (HMG) as a hypoglycemic principle of Spanish moss (Tillandsia usneoides). Author(s): Witherup KM, McLaughlin JL, Judd RL, Ziegler MH, Medon PJ, Keller WJ. Source: Journal of Natural Products. 1995 August; 58(8): 1285-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7595594&dopt=Abstract
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Insulinoma-induced hypoglycemic death in mice is prevented with beta cell-specific gene therapy. Author(s): Tirone TA, Fagan SP, Templeton NS, Wang X, Brunicardi FC. Source: Annals of Surgery. 2001 May; 233(5): 603-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11323498&dopt=Abstract
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Lactic acidosis and hypoglycemia in a patient with high-grade non-Hodgkin's lymphoma and elevated circulating TNF-alpha. Author(s): Durig J, Fiedler W, de Wit M, Steffen M, Hossfeld DK. Source: Annals of Hematology. 1996 February; 72(2): 97-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8597616&dopt=Abstract
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Long-term dietary treatment with increased amounts of fiber-rich low-glycemic index natural foods improves blood glucose control and reduces the number of hypoglycemic events in type 1 diabetic patients. Author(s): Giacco R, Parillo M, Rivellese AA, Lasorella G, Giacco A, D'Episcopo L, Riccardi G.
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Source: Diabetes Care. 2000 October; 23(10): 1461-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11023137&dopt=Abstract •
Mechanism of action of a hypoglycemic principle isolated from fenugreek seeds. Author(s): Puri D, Prabhu KM, Murthy PS. Source: Indian J Physiol Pharmacol. 2002 October; 46(4): 457-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12683221&dopt=Abstract
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Normal pressure hydrocephalus in diabetic patients with recurrent episodes of hypoglycemic coma. Author(s): Iino K, Yoshinari M, Yoshizumi H, Ichikawa K, Iwase M, Fujishima M. Source: Diabetes Research and Clinical Practice. 2000 February; 47(2): 105-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10670909&dopt=Abstract
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Oral beta-hydroxybutyrate supplementation in two patients with hyperinsulinemic hypoglycemia: monitoring of beta-hydroxybutyrate levels in blood and cerebrospinal fluid, and in the brain by in vivo magnetic resonance spectroscopy. Author(s): Plecko B, Stoeckler-Ipsiroglu S, Schober E, Harrer G, Mlynarik V, Gruber S, Moser E, Moeslinger D, Silgoner H, Ipsiroglu O. Source: Pediatric Research. 2002 August; 52(2): 301-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12149510&dopt=Abstract
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Phytochemical and hypoglycemic investigation of Casearia esculenta. Author(s): Choudhury KD, Basu NK. Source: Journal of Pharmaceutical Sciences. 1967 November; 56(11): 1405-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6060585&dopt=Abstract
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Probable mechanism of hypoglycemic activity of bassic acid, a natural product isolated from Bumelia sartorum. Author(s): Naik SR, Barbosa Filho JM, Dhuley JN, Deshmukh V. Source: Journal of Ethnopharmacology. 1991 May-June; 33(1-2): 37-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1943171&dopt=Abstract
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Programming pre-exercise snacks to prevent post-exercise hypoglycemia in intensively treated insulin-dependent diabetics. Author(s): Nathan DM, Madnek SF, Delahanty L. Source: Annals of Internal Medicine. 1985 April; 102(4): 483-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3838425&dopt=Abstract
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Quantitative measurement of islet glucagon response to hypoglycemia by confocal fluorescence imaging in diabetic rats: effects of phlorizin treatment. Author(s): Rastogi KS, Cooper RL, Shi ZQ, Vranic M.
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Source: Endocrine. 1997 December; 7(3): 367-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9657075&dopt=Abstract •
Repeated hypoglycemia and cognitive decline. A case report. Author(s): Akyol A, Kiylioglu N, Bolukbasi O, Guney E, Yurekli Y. Source: Neuroendocrinol Lett. 2003 February-April; 24(1-2): 54-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12743533&dopt=Abstract
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Resveratrol inhibits interleukin-6 production in cortical mixed glial cells under hypoxia/hypoglycemia followed by reoxygenation. Author(s): Wang MJ, Huang HM, Hsieh SJ, Jeng KC, Kuo JS. Source: Journal of Neuroimmunology. 2001 January 1; 112(1-2): 28-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11108930&dopt=Abstract
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Role of drugs in recovery of metabolic function of rat brain following severe hypoglycemia. Author(s): Benzi G, Villa RF, Dossena M, Vercesi L, Gorini A, Pastoris O. Source: Neurochemical Research. 1984 July; 9(7): 979-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6504232&dopt=Abstract
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Severe hypoglycemia as a presenting symptom of carbohydrate-deficient glycoprotein syndrome. Author(s): Babovic-Vuksanovic D, Patterson MC, Schwenk WF, O'Brien JF, Vockley J, Freeze HH, Mehta DP, Michels VV. Source: The Journal of Pediatrics. 1999 December; 135(6): 775-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10586187&dopt=Abstract
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Studies on the mechanism of “hypoglycemic” effect of nopal (Opuntia sp.). Author(s): Frati-Munari AC, Yever-Garces A, Islas-Andrade S, Ariza-Andraca CR, Chavez-Negrete A. Source: Arch Invest Med (Mex). 1987 January-March; 18(1): 7-12. English, Spanish. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3307675&dopt=Abstract
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Symptomatic hypoglycemia in children receiving oral purine analogues for treatment of childhood acute lymphoblastic leukemia. Author(s): Ziino O, Russo D, Orlando MA, Benigno V, Locatelli F, Arico M. Source: Medical and Pediatric Oncology. 2002 July; 39(1): 32-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12116076&dopt=Abstract
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The influence of silybin on the hepatotoxic and hypoglycemic effects of praseodymium and other lanthanides. Author(s): Strubelt O, Siegers CP, Younes M.
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Source: Arzneimittel-Forschung. 1980; 30(10): 1690-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7192108&dopt=Abstract •
The search for an optimized treatment of hypoglycemia. Carbohydrates in tablets, solutin, or gel for the correction of insulin reactions. Author(s): Slama G, Traynard PY, Desplanque N, Pudar H, Dhunputh I, Letanoux M, Bornet FR, Tchobroutsky G. Source: Archives of Internal Medicine. 1990 March; 150(3): 589-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2310277&dopt=Abstract
Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: •
Alternative Medicine Foundation, Inc.: http://www.herbmed.org/
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AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats
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Chinese Medicine: http://www.newcenturynutrition.com/
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drkoop.com®: http://www.drkoop.com/InteractiveMedicine/IndexC.html
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Family Village: http://www.familyvillage.wisc.edu/med_altn.htm
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Google: http://directory.google.com/Top/Health/Alternative/
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Healthnotes: http://www.healthnotes.com/
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MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine
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Open Directory Project: http://dmoz.org/Health/Alternative/
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HealthGate: http://www.tnp.com/
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WebMD®Health: http://my.webmd.com/drugs_and_herbs
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
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Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/
The following is a specific Web list relating to hypoglycemia; 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 Alcoholism Source: Integrative Medicine Communications; www.drkoop.com Chronic Fatigue Syndrome Source: Healthnotes, Inc.; www.healthnotes.com
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Colic Source: Healthnotes, Inc.; www.healthnotes.com Diabetes Source: Healthnotes, Inc.; www.healthnotes.com Diabetes Source: Prima Communications, Inc.www.personalhealthzone.com Diabetes Mellitus Source: Integrative Medicine Communications; www.drkoop.com Diarrhea Source: Healthnotes, Inc.; www.healthnotes.com Eating Disorders Source: Healthnotes, Inc.; www.healthnotes.com Fainting Source: Integrative Medicine Communications; www.drkoop.com Fibromyalgia Source: Integrative Medicine Communications; www.drkoop.com Hyperkalemia Source: Integrative Medicine Communications; www.drkoop.com Low Blood Sugar Source: Integrative Medicine Communications; www.drkoop.com Ménière's Disease Source: Healthnotes, Inc.; www.healthnotes.com Migraine Headaches Source: Healthnotes, Inc.; www.healthnotes.com PMS Source: Integrative Medicine Communications; www.drkoop.com Premenstrual Syndrome Source: Integrative Medicine Communications; www.drkoop.com Restless Legs Syndrome Source: Healthnotes, Inc.; www.healthnotes.com Syncope Source: Integrative Medicine Communications; www.drkoop.com Tension Headache Source: Integrative Medicine Communications; www.drkoop.com
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Vertigo Source: Healthnotes, Inc.; www.healthnotes.com •
Alternative Therapy Detoxification Therapy Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10119,00.html Naturopathy Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,722,00.html
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Herbs and Supplements Acanthopanax Senticosus Source: Integrative Medicine Communications; www.drkoop.com Achillea Alternative names: Yarrow; Achillea millefolium L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Aloe Alternative names: Aloe vera, Aloe barbadensis Source: Healthnotes, Inc.; www.healthnotes.com Aloe Alternative names: Aloe Vera Source: Integrative Medicine Communications; www.drkoop.com Aloe Vera Alternative names: Aloe Source: Integrative Medicine Communications; www.drkoop.com Alpha Lipoic Acid Source: Healthnotes, Inc.; www.healthnotes.com Alpha-lipoic Acid Source: Integrative Medicine Communications; www.drkoop.com Althaea Officinalis Source: Integrative Medicine Communications; www.drkoop.com American Ginseng Alternative names: Panax quinquefolium Source: Integrative Medicine Communications; www.drkoop.com
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Aralia Alternative names: Spikenard; Aralia sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Arctium Lappa Source: Integrative Medicine Communications; www.drkoop.com Arctium Minus Source: Integrative Medicine Communications; www.drkoop.com Astragalus Sp Alternative names: Vetch, Rattlepod, Locoweed; Astragalus sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Bitter Melon Alternative names: Momordica charantia Source: Healthnotes, Inc.; www.healthnotes.com Blue-Green Algae Source: Integrative Medicine Communications; www.drkoop.com Brewer’s Yeast Source: Healthnotes, Inc.; www.healthnotes.com Bryonia Bryony Alternative names: Bryony; Bryonia sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Eleuthero Alternative names: Siberian Ginseng, Eleuthero; Acanthopanax/Eleutherococcus senticosus Rupr. & Maxim. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Eleuthero Alternative names: Eleutherococcus senticosus, Acanthopanax senticosus Source: Healthnotes, Inc.; www.healthnotes.com Eleuthero Source: Integrative Medicine Communications; www.drkoop.com Eleutherococcus Senticosus Source: Integrative Medicine Communications; www.drkoop.com Eugenia Clove Alternative names: Cloves; Eugenia sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Fenugreek Source: Prima Communications, Inc.www.personalhealthzone.com Glimepiride Source: Healthnotes, Inc.; www.healthnotes.com
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Glucomannan Source: Healthnotes, Inc.; www.healthnotes.com Glyburide Source: Healthnotes, Inc.; www.healthnotes.com Glycyrrhiza1 Alternative names: Licorice; Glycyrrhiza glabra L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Gymnema Alternative names: Gurmar; Gymnema sylvestre Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Gymnema Alternative names: Gymnema sylvestre Source: Healthnotes, Inc.; www.healthnotes.com Gymnema Source: Prima Communications, Inc.www.personalhealthzone.com Hibiscus Alternative names: Hibiscus, Roselle; Hibiscus sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Insulin Source: Healthnotes, Inc.; www.healthnotes.com Insulin Alternative names: Humalog, Humulin, Iletin, Novolin, Velosulin Source: Prima Communications, Inc.www.personalhealthzone.com Lavandula Alternative names: Lavender; Lavandula sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Marshmallow Alternative names: Althea officinalis Source: Healthnotes, Inc.; www.healthnotes.com Marshmallow Alternative names: Althaea officinalis Source: Integrative Medicine Communications; www.drkoop.com Marshmallow Source: Prima Communications, Inc.www.personalhealthzone.com Momordica Alternative names: Bitter Gourd, Karela; Momordica charantia Linn. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org
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Ocimum Alternative names: Basil, Albahaca; Ocimum basilicum Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Oral Hypoglycemics Source: Prima Communications, Inc.www.personalhealthzone.com Paba Source: Healthnotes, Inc.; www.healthnotes.com Panax Alternative names: Ginseng; Panax ginseng Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Panax Quinquefolium Source: Integrative Medicine Communications; www.drkoop.com Passiflora Alternative names: Passion Flower; Passiflora alata L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Siberian Ginseng Alternative names: Eleutherococcus senticosus, Acanthopanax senticosus, Eleuthero Source: Integrative Medicine Communications; www.drkoop.com Spirulina Alternative names: Blue-green Algae Source: Integrative Medicine Communications; www.drkoop.com Swertia Alternative names: Swertia sp Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Syzygium Clove Alternative names: Clove, Jamun; Syzygium sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Trigonella Alternative names: Fenugreek; Trigonella foenum graecum L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Vanadate Source: Integrative Medicine Communications; www.drkoop.com Vanadyl 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
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dedicated to complementary and alternative medicine. To access this page, go to the MEDLINEplus site at http://www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources.
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CHAPTER 4. DISSERTATIONS ON HYPOGLYCEMIA Overview In this chapter, we will give you a bibliography on recent dissertations relating to hypoglycemia. We will also provide you with information on how to use the Internet to stay current on dissertations. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical dissertations that use the generic term “hypoglycemia” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on hypoglycemia, we have not necessarily excluded non-medical dissertations in this bibliography.
Dissertations on Hypoglycemia ProQuest Digital Dissertations, the largest archive of academic dissertations available, is located at the following Web address: http://wwwlib.umi.com/dissertations. From this archive, we have compiled the following list covering dissertations devoted to hypoglycemia. You will see that the information provided includes the dissertation’s title, its author, and the institution with which the author is associated. The following covers recent dissertations found when using this search procedure: •
Characterization of Neural Mechanisms Involved in Hypoglycemic Detection at the Portal Vein by Fujita, Satoshi; PhD from University of Southern California, 2002, 103 pages http://wwwlib.umi.com/dissertations/fullcit/3073778
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Effect of Carbohydrate Supplementation on Metabolism and Performance during Prolonged Exercise (hypoglycemia, Fatigue, Plasma Glucose, Cycling) by Coggan, Andrew Richard, PhD from The University of Texas at Austin, 1986, 99 pages http://wwwlib.umi.com/dissertations/fullcit/8705984
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Holistic Approach to Hypoglycemia by Weady, Dorothy R. Gemino, PhD from Brigham Young University, 1980, 165 pages http://wwwlib.umi.com/dissertations/fullcit/8102735
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Neurochemical Mechanisms in the Hypothalamus and Attenuation of Compensatory Hormone Responses to Recurrent Hypoglycemia by De Vries, Martin Goos; PhD from University of Illinois at Urbana-champaign, 2002, 121 pages http://wwwlib.umi.com/dissertations/fullcit/3070287
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Role of Insulin in the Abnormal Glucagon Secretory Response to Hypoglycemia in Type 1 Diabetes by Zhu, Ying Y.; MS from Southern Connecticut State University, 2002, 24 pages http://wwwlib.umi.com/dissertations/fullcit/1407776
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The Hypoglycemic Factor in Pastoral Counseling by Callaway, Chaudoin, Iii, Dmin from Drew University, 1981, 185 pages http://wwwlib.umi.com/dissertations/fullcit/8119819
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The Role of Forebrain Glucoreceptors in the Counter-regulatory Response to Insulininduced Hypoglycemia by Cane, Patricia Irene, PhD from University of Southern California, 1985 http://wwwlib.umi.com/dissertations/fullcit/f1583877
Keeping Current Ask the medical librarian at your library if it has full and unlimited access to the ProQuest Digital Dissertations database. From the library, you should be able to do more complete searches via http://wwwlib.umi.com/dissertations.
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CHAPTER 5. CLINICAL TRIALS AND HYPOGLYCEMIA Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning hypoglycemia.
Recent Trials on Hypoglycemia The following is a list of recent trials dedicated to hypoglycemia.8 Further information on a trial is available at the Web site indicated. •
Diagnosing and Treating Low Blood Sugar Levels Condition(s): Hypoglycemia; Insulinoma Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Purpose - Excerpt: Hypoglycemia is the term used to refer to lower than normal levels of blood sugar. This study will continue to research the causes of hypoglycemia. Patients involved in the study will be admitted to the Clinical Center of the National Institutes of Health and undergo tests for evaluating blood sugar. Patients will be required to refrain from eating for a set period of time and will undergo blood tests for insulin levels and several other specific diagnostic tests related to insulin secretion. The patients will be under supervision and will be provided with appropriate medical and surgical attention as needed. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001276
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Disorders of Systemic Glucose Balance Condition(s): Hypoglycemia Study Status: This study is currently recruiting patients.
8
These are listed at www.ClinicalTrials.gov.
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Sponsor(s): National Center for Research Resources (NCRR) Purpose - Excerpt: We wish to identify people with hypoglycemia (low blood sugar) and ultimately determine why the blood sugar levels are so low. To do so, we will contrast the responses of patients suspected to have hypoglycemia with those of healthy subjects during standardized tests. Those tests may include: 1) a controlled hypoglycemia produced by administration of insulin, a blood sugar-lowering hormone, and sugar, 2) a formula meal, and 3) a period of up to 72 hours without food. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006508 •
Does Islet Transplantation Eliminate Hypoglycemia? Condition(s): Diabetes Mellitus Study Status: This study is not yet open for patient recruitment. Sponsor(s): National Center for Research Resources (NCRR) Purpose - Excerpt: Low blood sugar (hypoglycemia) is a recurrent problem for many people with diabetes. Successful transplantation of clusters (islets) of normal cells, that include those which produce the sugar-lowering hormone insulin, from the pancreas of a person who did not have diabetes into a person with diabetes should eliminate high blood sugar levels. We wish to determine if it will also eliminate low blood sugar. To do so we will give insulin to lower the blood sugar, measure the levels of the hormones that normally raise blood sugar levels (e.g., glucagon and epinephrine) and then stop the insulin and see if blood sugar levels return to normal. Because we anticipate that the transplanted islets will produce insulin, but not glucagon, this study may also tell us if regulated insulin production alone can prevent hypoglycemia in humans. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006068
Keeping Current on Clinical Trials The U.S. National Institutes of Health, through the National Library of Medicine, has developed ClinicalTrials.gov to provide current information about clinical research across the broadest number of diseases and conditions. The site was launched in February 2000 and currently contains approximately 5,700 clinical studies in over 59,000 locations worldwide, with most studies being conducted in the United States. ClinicalTrials.gov receives about 2 million hits per month and hosts approximately 5,400 visitors daily. To access this database, simply go to the Web site at http://www.clinicaltrials.gov/ and search by “hypoglycemia” (or synonyms). While ClinicalTrials.gov is the most comprehensive listing of NIH-supported clinical trials available, not all trials are in the database. The database is updated regularly, so clinical trials are continually being added. The following is a list of specialty databases affiliated with the National Institutes of Health that offer additional information on trials:
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•
For clinical studies at the Warren Grant Magnuson Clinical Center located in Bethesda, Maryland, visit their Web site: http://clinicalstudies.info.nih.gov/
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For clinical studies conducted at the Bayview Campus in Baltimore, Maryland, visit their Web site: http://www.jhbmc.jhu.edu/studies/index.html
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For cancer trials, visit the National Cancer Institute: http://cancertrials.nci.nih.gov/
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For eye-related trials, visit and search the Web page of the National Eye Institute: http://www.nei.nih.gov/neitrials/index.htm
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For heart, lung and blood trials, visit the Web page of the National Heart, Lung and Blood Institute: http://www.nhlbi.nih.gov/studies/index.htm
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For trials on aging, visit and search the Web site of the National Institute on Aging: http://www.grc.nia.nih.gov/studies/index.htm
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For rare diseases, visit and search the Web site sponsored by the Office of Rare Diseases: http://ord.aspensys.com/asp/resources/rsch_trials.asp
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For alcoholism, visit the National Institute on Alcohol Abuse and Alcoholism: http://www.niaaa.nih.gov/intramural/Web_dicbr_hp/particip.htm
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For trials on infectious, immune, and allergic diseases, visit the site of the National Institute of Allergy and Infectious Diseases: http://www.niaid.nih.gov/clintrials/
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For trials on arthritis, musculoskeletal and skin diseases, visit newly revised site of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health: http://www.niams.nih.gov/hi/studies/index.htm
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For hearing-related trials, visit the National Institute on Deafness and Other Communication Disorders: http://www.nidcd.nih.gov/health/clinical/index.htm
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For trials on diseases of the digestive system and kidneys, and diabetes, visit the National Institute of Diabetes and Digestive and Kidney Diseases: http://www.niddk.nih.gov/patient/patient.htm
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For drug abuse trials, visit and search the Web site sponsored by the National Institute on Drug Abuse: http://www.nida.nih.gov/CTN/Index.htm
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For trials on mental disorders, visit and search the Web site of the National Institute of Mental Health: http://www.nimh.nih.gov/studies/index.cfm
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For trials on neurological disorders and stroke, visit and search the Web site sponsored by the National Institute of Neurological Disorders and Stroke of the NIH: http://www.ninds.nih.gov/funding/funding_opportunities.htm#Clinical_Trials
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CHAPTER 6. PATENTS ON HYPOGLYCEMIA Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.9 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “hypoglycemia” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on hypoglycemia, we have not necessarily excluded non-medical patents in this bibliography.
Patents on Hypoglycemia By performing a patent search focusing on hypoglycemia, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We will tell you how to obtain this information later in the chapter. The following is an 9Adapted
from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.
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example of the type of information that you can expect to obtain from a patent search on hypoglycemia: •
2-substituted piperidine analogs and their use as subtype-selective NMDA receptor antagonists Inventor(s): Bigge; Christopher F. (Ann Arbor, MI), Cai; Sui Xiong (Foothill, CA), Guzikowski; Anthony P. (Eugene, OR), Keana; John F. W. (Eugene, OR), Lan; Nancy C. (South Pasadena, CA), Weber; Eckard (Laguna Beach, CA), Woodward; Richard (Aliso Viejo, CA) Assignee(s): Cocensys, Inc. (Irvine, CA), Warner-Lambert Company (Morris Plains, NJ) Patent Number: 6,124,317 Date filed: November 18, 1998 Abstract: Novel 2-substituted piperidine analogs, pharmaceutical compositions containing the same and the method of using 2-substituted piperidine analogs as selectively active antagonists of N-methyl-D-aspartatc (NMDA) receptor subtypes for treating conditions such as stroke, cerebral ischemia, central nervous system trauma, hypoglycemia, anxiety, convulsions, amioglycoside antibiotics-induced hearing loss, migraine headaches, chronic pain, glaucoma, CMV retinitis, psychosis, urinary incontinence, opioid tolerance or withdrawal, or neurodegenerative disorders, such as lathyrism, Alzheimer's Disease, Parkinsonism and Huntington's Disease are described. Excerpt(s): This invention is related to 2-substituted piperidine analogs. The analogs are selectively active as antagonists of N-methyl-D-aspartate (NMDA) receptor subtypes. The invention is also directed to the use of 2-substituted piperidine analogs as neuroprotective agents for treating conditions such as stroke, cerebral ischemia, central nervous system trauma, hypoglycemia, anxiety, convulsions, aminoglycoside antibiotics-induced hearing loss, migraine headaches, chronic pain, glaucoma, CMV retinitis, psychosis, urinary incontinence, opioid tolerance or withdrawal, or neurodegenerative disorders such as lathyrism, Alzheimer's Disease, Parkinsonism and Huntington's Disease. Excessive excitation by neurotransmitters can cause the degeneration and death of neurons. It is believed that this degeneration is in part mediated by the excitotoxic actions of the excitatory amino acids (EAA) glutamate and aspartate at the N-methyl-D-Aspartate (NMDA) receptor. This excitotoxic action is considered responsible for the loss of neurons in cerebrovascular disorders such as cerebral ischemia or cerebral infarction resulting from a range of conditions, such as thromboembolic or hemorrhagic stroke, cerebral vasospasms, hypoglycemia, cardiac arrest, status epilepticus, perinatal asphyxia, anoxia such as from drowning, pulmonary surgery and cerebral trauma, as well as lathyrism, Alzheimer's Disease, Parkinson's Disease and Huntington's Disease. Ar is aryl or heteroaryl, each of which may be optionally substituted. 2-[2-(3,4-Dichlorophenoxy)ethyl]-1-cinnamylpiperidine oxalate hemihydrate and 4-[2-(2-Dibenzofuranyloxy)ethyl]-1-cinnamylpiperidine oxalate are exemplified. The compounds of this reference are said to be useful for treating anoxia, ischaemia, such as stroke, migraine, epilepsy, traumatic head injury, AIDS-related dementia, neurodegenerative diseases and drug addiction withdrawal. This reference does not disclose or suggest NMDA receptor activity, let alone selective NMDA receptor subtype antagonism. Web site: http://www.delphion.com/details?pn=US06124317__
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4-substituted piperidine analogs and their use as subtype selective NMDA receptor antagonists Inventor(s): Bigge; Christopher F. (Ann Arbor, MI), Cai; Sui Xiong (Foothill, CA), Guzikowski; Anthony P. (Eugene, OR), Keana; John F. W. (Eugene, OR), Lan; Nancy C. (South Pasadena, CA), Weber; Eckard (Laguna Beach, CA), Woodward; Richard (Aliso Viejo, CA), Yuen; Po-Wai (Ann Arbor, MI), Zhou; Zhang-Lin (Irvine, CA) Assignee(s): Cocensys, Incorporated (Irvine, CA), Warner-Lambert Company (Morris Plains, NJ) Patent Number: 6,124,323 Date filed: September 16, 1998 Abstract: Novel 4-substituted piperidine analogs, pharmaceutical compositions containing the same and the method of using 4-substituted piperidine analogs are selective active antagonists of N-methyl-D-aspartate (NMDA) receptor subtypes for treating conditions such as stroke, cerebral ischemia, central nervous system trauma, hypoglycemia, psychosis, anxiety, migraine headaches, glaucoma, CMV retinitis, aminoglycoside antibiotics-induced hearing loss, convulsions, chronic pain, opioid tolerance or withdrawal, urinary incontinence or neurodegenerative disorders, such as lathyrism, Alzheimer's Disease, Parkinsonism and Huntington's Disease are described. Excerpt(s): This invention is related to 4-substituted piperidine analogs, including hydroxypiperidine and tetrahydropyridine analogs. The analogs are selectively active as antagonists of N-methyl-D-aspartate (NMDA) receptor subtypes. The invention is also directed to the use of 4-substituted piperidine analogs as neuroprotective agents for treating conditions such as stroke, cerebral ischemia, central nervous system trauma, hypoglycemia, anxiety, psychosis, glaucoma, CMV retinitis, urinary incontinence, aminoglycoside antibiotics-induced hearing loss, convulsions, migraine headache, chronic pain, opioid tolerance or withdrawal, or neuro-degenerative disorders such as lathyrism, Alzheimer's Disease, Parkinsonism and Huntington's Disease. Excessive excitation by neurotransmitters can cause the degeneration and death of neurons. It is believed that this degeneration is in part mediated by the excitotoxic actions of the excitatory amino acids (EAA) glutamate and aspartate at the N-methyl-D-Aspartate (NMDA) receptor. This excitotoxic action is considered responsible for the loss of neurons in cerebrovascular disorders such as cerebral ischemia or cerebral infarction resulting from a range of conditions, such as thromboembolic or hemorrhagic stroke, cerebral vasospasms, hypoglycemia, cardiac arrest, status epilepticus, perinatal asphyxia, anoxia such as from drowning, pulmonary surgery and cerebral trauma, as well as lathyrism, Alzheimer's Disease, Parkinson's Disease and Huntington's Disease. Other piperidine derivatives having aryl alkanol functionality are disclosed by PCT International Publication No. WO 93/11107 (for treating hypoxia and ischaemia), International Publication No. WO 94/10166 (for treating stroke, addiction, pain, epilepsy, psychosis, traumatic brain injury and CNS degenerative diseases), EP 0398578 (for treating stroke or CNS degenerative diseases, Alzheimer's disease, Huntington's disease and Parkinson's disease) and PCT International Publication No. WO 93/02052 (for treating stroke, traumatic injury to the brain and spinal cord, and neuronal degenerative diseases). Similar to EP 0648744, each of these references requires a piperidine derivative having an alkyl hydroxy or keto group alpha to the aryl group of the N-1 substituent. The 4-substituted piperidine analogs of this invention differ in kind from the piperidine derivatives of these references. Web site: http://www.delphion.com/details?pn=US06124323__
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Alkyl, azido, alkoxy and fluoro-substituted and fused quinoxalinediones and the use thereof as glycine receptor antagonist Inventor(s): Cai; Sui Xiong (Irvine, CA), Keana; John F. W. (Eugene, OR), Kher; Sunil (Eugene, OR), Weber; Eckard (Laguna Beach, CA) Assignee(s): CoCensys, Inc. (Irvine, CA), State of Oregon, Acting by and Through the Oregon State Board of Higher (Eugene, OR), The Regents of the University of California (Oakland, CA) Patent Number: 6,147,075 Date filed: August 18, 1999 Abstract: Methods of treating or preventing neuronal loss associated with stroke, ischemia, CNS trauma, hypoglycemia, and surgery, as well as treating neurodegenerative diseases including Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's disease, and Down's syndrome, treating or preventing the adverse consequences of the hyperactivity of the excitatory amino acids, as well as treating anxiety, chronic pain, convulsions, and inducing anesthesia are disclosed by administering to an animal in need of such treatment an alkyl or azido-substituted 1,4dihydroquinoxaline-2,3-dione or pharmaceutically acceptable salts thereof, which have high binding to the glycine receptor. Excerpt(s): The present invention is in the field of medicinal chemistry and relates to compounds that have a high affinity for the glycine binding site, lack PCP side effects, and cross the blood brain barrier at high levels. In particular, the present invention relates to novel alkyl, azido, alkoxy, fluoro-substituted, and fused 1,4dihydroquinoxaline-2,3-diones and their use to treat or prevent neuronal degeneration associated with ischemia, pathophysiologic conditions associated with neuronal degeneration, convulsions, anxiety, chronic pain, and to induce anesthesia. Glutamate is thought to be the major excitatory neurotransmitter in the brain. There are three major subtypes of glutamate receptors in the CNS. These are commonly referred to as kainate, AMPA, and N-methyl-D-aspartate (NMDA) receptors (Watkins and Olverman, Trends in Neurosci. 7:265-272 (1987)). NMDA receptors are found in the membranes of virtually every neuron in the brain. NMDA receptors are ligand-gated cation channels that allow Na.sup.+, K.sup.+, and Ca.sup.++ to permeate when they are activated by glutamate or aspartate (non-selective, endogenous agonists) or by NMDA (a selective, synthetic agonist) (Wong and Kemp, Ann. Rev. Pharmacol. Toxicol. 31:401-425 (1991)). Glutamate alone cannot activate the NMDA receptor. In order to become activated by glutamate, the NMDA receptor channel must first bind glycine at a specific, high affinity, glycine binding site that is separate from the glutamate/NMDA binding site on the receptor protein (Johnson and Ascher, Nature 325:329-331 (1987)). Glycine is therefore an obligatory co-agonist at the NMDA receptor/channel complex (Kemp, J. A., et al., Proc. Natl. Acad. Sci. USA 85:6547-6550 (1988)). Web site: http://www.delphion.com/details?pn=US06147075__
Patents 145
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Alternate crystal form of Tazofelone Inventor(s): Hansen; Marvin M (Indianapolis, IN), Harkness; Allen R (Indianapolis, IN), Reutzel; Susan M (Indianapolis, IN) Assignee(s): Eli Lilly and Company (Indianapolis, IN) Patent Number: 6,063,799 Date filed: February 25, 1998 Abstract: The instant invention provides novel crystalline Form II of (.+-.)-5-{[3,5bis(1,1dimethylethyl)-4-hydroxyphenyl]methyl}-4-thiazolidin one having an x-ray powder diffraction patter with specific d spacings useful for treating inflammation, inflammatory bowel disease, allergies, arthritis and hypoglycemia utilizing the novel physical form as well as pharmaceutical compositions containing the same. A process for preparing Form II Tazofelone is described. Excerpt(s): This invention relates to a novel physical form of (.+-.)-5-{[3,5-bis(1,1dimethylethyl)-4-hydroxyphenyl]methyl}-4-thiazolidi none useful in the treatment of inflammation, inflammatory bowel disease (hereinafter IBD), allergies, arthritis, hypoglycemia and muscular dystrophy and in preventing ischemia induced cell damage. Benzyl-substituted rhodanine derivatives are known to be active in treating inflammation, inflammatory bowel disease (hereinafter IBD), allergies, arthritis, hypoglycemia and muscular dystrophy and in preventing ischemia induced cell damage. For example, U.S. Pat. No. 5,216,002 discloses that certain benzyl-substituted rhodanine derivatives are useful for treating IBD. EPO Publication No. 391644, on the other hand, discloses the effectiveness of such compounds for treating inflammation, arthritis, and muscular dystrophy and for preventing ischemia induced cell damage. EPO Publication No. 343643 describes the use of such compounds for treating allergies and inflammation, while EPO Publication No. 587377 discloses these compounds as being effective in treating hypoglycemia. Tazofelone is particularly useful in treating inflammatory bowel diseases (IBD), ulcerative colitis and Chrohn's disease. Web site: http://www.delphion.com/details?pn=US06063799__
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Amylin agonist peptides and uses therefor Inventor(s): Albrecht; Elisabeth (San Diego, CA), Gaeta; Laura S. L. (La Jolla, CA), Jones; Howard (Poway, CA) Assignee(s): Amylin Pharmaceuticals, Inc. (San Diego, CA) Patent Number: 6,610,824 Date filed: December 6, 1999 Abstract: Agonist analogs of amylin and related pharmaceutical compositions, and methods of treatment of diabetes and other insulin-requiring states, as well as methods of treatment of hypoglycemia, are provided. Excerpt(s): The field of the invention is medicine, particularly the treatment and prevention of hypoglycemic conditions and other conditions in which enhanced amylin action is of benefit, including insulin-requiring states such as diabetes mellitus. More specifically, the invention relates to the preparation and use of agonist analogues of the peptide hormone amylin. Diabetes mellitus is a serious metabolic disease that is defined by the presence of chronically elevated levels of blood glucose (hyperglycemia). This state of hyperglycemia is the result of a relative or absolute lack of activity of the peptide
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hormone, insulin. Insulin is produced and secreted by the.beta. cells of the pancreas. Insulin is reported to promote glucose utilization, protein synthesis, and the formation and storage of neutral lipids. Glucose, the principal source of carbohydrate energy, is stored in the body as glycogen, a form of polymerized glucose, which may be converted back into glucose to meet metabolism requirements. Under normal conditions, insulin is secreted at both a basal rate and at enhanced rates following glucose stimulation, all to maintain metabolic homeostasis by the conversion of glucose into glycogen. The term diabetes mellitus encompasses several different hyperglycemic states. These states include Type 1 (insulin-dependent diabetes mellitus or IDDM) and Type 2 (non-insulindependent diabetes mellitus or NIDDM) diabetes. The hyperglycemia present in individuals with Type I diabetes is associated with deficient, reduced, or nonexistent levels of insulin which are insufficient to maintain blood glucose levels within the physiological range. Treatment of Type 1 diabetes involves administration of replacement doses of insulin, generally by the parenteral route. The hyperglycemia present in individuals with Type II diabetes is initially associated with normal or elevated levels of insulin; however, these individuals are unable to maintain metabolic homeostasis due to a state of insulin resistance in peripheral tissues and liver and, as the disease advances, due to a progressive deterioration of the pancreatic.beta. cells which are responsible for the secretion of insulin. Thus, initial therapy of Type 2 diabetes may be based on diet and lifestyle changes augmented by therapy with oral hypoglycemic agents such as sulfonylureas. Insulin therapy is often required, however, especially in the latter stages of the disease, in attempting to produce some control of hyperglycemia and minimize complications of the disease. Thus, many Type 2 diabetics ultimately require insulin in order to survive. Web site: http://www.delphion.com/details?pn=US06610824__ •
Branched chain amino acid-dependent aminotransferase inhibitors and their use in the treatment of neurodegenerative diseases Inventor(s): Hays; Sheryl Jeanne (Ann Arbor, MI), Hu; Lain-Yen (Ann Arbor, MI), Lei; Huangshu (Ann Arbor, MI), Scholten; Jeffrey David (Ann Arbor, MI), Wustrow; David Juergen (Ann Arbor, MI) Assignee(s): Pfizer Inc. (New York, NY) Patent Number: 6,632,831 Date filed: November 26, 2002 Abstract: The invention relates to BCAT inhibitors and the use thereof for treating or preventing neuronal loss associated with stroke, ischemia, CNS trauma, hypoglycemia and surgery, as well as treating neurodegenerative diseases including Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's disease and Down's syndrome, treating or preventing the adverse consequences of the overstimulation of the excitatory amino acids, treating anxiety, psychosis, convulsions, aminoglycoside antibioticsinduced hearing loss, migraine headache, chronic pain, neuropathic pain, Parkinson's disease, diabetic retinopathy, glaucoma, CMV retinitis, urinary incontinence, opioid tolerance or withdrawal, and inducing anesthesia, as well as for enhancing cognition. Excerpt(s): This invention is related to branched chain amino acid-dependent amino transferase (BCAT) inhibitors. The invention is also directed to the use of BCAT inhibitors as neuro-protective agents for treating conditions such as stroke, cerebral ischemia, central nervous system trauma, hypoglycemia, anxiety, convulsions, aminoglycoside antibiotics-induced hearing loss, migraine headaches, chronic pain,
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neuropathic pain, glaucoma, CMV retinitis, diabetic retinopathy, psychosis, urinary incontinence, opioid tolerance or withdrawal, or neuro-degenerative disorders such as lathyrism, Alzheimer's disease, Parkinsonism, amyotrophic lateral sclerosis (ALS), and Huntington's Disease. Excessive excitation by neurotransmitters can cause the degeneration and death of neurons. It is believed that this degeneration is in part mediated by the excitotoxic actions of the excitatory amino acids (EAA) glutamate and aspartate at the N-methyl-D-aspartate (NMDA) receptor. This excitotoxic action is considered responsible for the loss of neurons in cerebrovascular disorders such as cerebral ischemia or cerebral infarction resulting from a range of conditions, such as thromboembolic or hemorrhagic stroke, cerebral vasospasms, hypoglycemia, cardiac arrest, status epilepticus, perinatal asphyxia, anoxia such as from drowning, pulmonary surgery and cerebral trauma, as well as lathyrism, Alzheimer's disease, Parkinson's disease, and Huntington's disease. Excitatory amino acid receptor antagonists that block NMDA receptors are recognized for usefulness in the treatment of disorders. NMDA receptors are intimately involved in the phenomenon of excitotoxicity, which may be a critical determinant of outcome of several neurological disorders. Disorders known to be responsive to blockade of the NMDA receptor include acute cerebral ischemia (stroke or cerebral trauma, for example), muscular spasm, convulsive disorders, neuropathic pain and anxiety, and may be a significant causal factor in chronic neurodegenerative disorders such as Parkinson's disease (Klockgether T., Turski L., Ann. Neurol., 1993;34:585-593), human immunodeficiency virus (HIV) related neuronal injury, amyotrophic lateral sclerosis (ALS), Alzheimer's disease (Francis P. T., Sims N. R., Procter A. W., Bowen D. M., J. Neurochem., 1993;60(5):1589-1604, and Huntington's disease (see Lipton S., TINS, 1993;16(12):527-532; Lipton S. A., Rosenberg P. A., New Eng. J. Med., 1994;330(9):613-622; and Bigge C. F., Biochem. Pharmacol., 1993;45:15471561, and referenced cited therein.) NMDA receptor antagonists may also be used to prevent tolerance to opiate analgesia or to help control withdrawal symptoms from addictive drugs (Eur. Pat. Appl. 488,959A). Web site: http://www.delphion.com/details?pn=US06632831__ •
Coffee substitute Inventor(s): Zhao; Iris G (1969 Zonal Ave., Los Angeles, CA 90033) Assignee(s): none reported Patent Number: 6,171,635 Date filed: January 27, 1999 Abstract: A coffee-type beverage base is prepared by light roast method under 200.degree. C. and originated from grain and legume. This coffee substitute has a pleasant aroma, and can be used as a carrier of nutritional supplement or herb therapy as well as an additive of coffee, tea, or chocolate. This novel drink is especially suitable for individuals who suffer from conditions making them coffee intolerant, e.g., pregnancy, or those who suffer form hypoglycemia, hypertension, arrhythmia, insomnia, or gastric irritation. Excerpt(s): The present invention relates to coffee substitutes and, more particularly, to a non-caffeine beverage base produced from grain and legume, which provide synergetic coaction among the ingredients. Until the middle of this century, development of medical treatment for human disease was intimately connected with the plant kingdom. Major breakthroughs such as digitalis, aspirin, morphine, vincristin and antibiotics have resulted from the study and usage of natural products. Gaps remain between the
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prescribed pharmaceutical pills and natural food therapy. The human body contains about 55-60% water. Humans by nature enjoy drinking liquids. Liquids containing energy supply, mineral, nutritional supplement and medicine are always the first choice for a patient after surgery and IV nutrition. Coffee possesses a pleasant aroma and is an enjoyable taste experience that many believe reduces stress during the workday. Consequently, the United States consumes about 70% of the world's coffee crop, or about 3 cups a day for each American. Coffee beverages contain about 100 mg caffeine per cup (per 8 ounces). Coffee stimulates the central nervous system, increases diuresis, dilates the vascular system and combats sleep, which is possibly linked to the caffeinemediated glycogen sparing effect secondary to an increased rate of lipolysis. Web site: http://www.delphion.com/details?pn=US06171635__ •
Diabetic supplement bar Inventor(s): Bell; Stacey J. (56 Amherst Rd., Belmont, MA 02178), Bistrian; Bruce R. (229 Argilla Rd., Ipswich, MA 01938), Forse; R. Armour (50 Fisher Ave., Brookline, MA 02146), Jones; Robert C. (109 Cross St., Belmont, MA 02178) Assignee(s): none reported Patent Number: 6,156,738 Date filed: February 1, 1999 Abstract: A novel diabetic supplement bar which includes about 10-60% by weight simple carbohydrate, about 1-25% by weight protein, about 2-40% by weight lipid and about 1-60%, preferably about 5-35% by weight complex carbohydrate. This formulation is particularly useful for the treatment or prevention of nighttime hypoglycemia in diabetic patients who require insulin injections. Excerpt(s): The present invention relates to the control of nighttime hypoglycemia in diabetics who require insulin injections. The invention utilizes a food bar which can be administered at bedtime to control blood glucose levels. The results of a major study (Diabetes Control and Complication Trial)(Dawson, Clinical Diabetes 11:88-96, 1993), including over 1,400 diabetic patients who require regular insulin administrations, have indicated that patients who maintain blood sugar levels as close as possible to normal have fewer complications resulting in neuropathy, retinopathy, and kidney disease. To accomplish this result, many patients with diabetes today follow a strict regimen, known as the "tight control" regimen. This regimen requires that the patients closely monitor their blood sugar levels (e.g., multiple tests/day), judiciously use insulin in multiple doses, and strictly adhere to their diet. The unwanted side effect of tight glucose control is, however, that patients following this regimen have a three-fold increase in hypoglycemic events, more than half of which occur at nighttime. Hypoglycemia is a dangerous condition which develops quickly and can cause neurologic damage as well as cause a patient to go into an unconscious state, and, in rare instances, a coma. Physicians want patients to be aware of the symptoms of hypoglycemia, e.g., coldness, shakiness, palpitations, and altered mentation, in order to avoid this condition. However, during sleep, the patients are not aware that they are developing hypoglycemia, so it is cricial to develop a treatment which can prevent this condition from developing at nighttime. Web site: http://www.delphion.com/details?pn=US06156738__
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Glutamine:fructose-6-phosphate amidotransferase, its production and use Inventor(s): Hikichi; Yukiko (Tsukuba, JP), Nishi; Kazunori (Tsukuba, JP), Shintani; Yasushi (Tsukuba, JP) Assignee(s): Tekeda Chemical Industries, Ltd. (Osaka, JP) Patent Number: 6,207,431 Date filed: October 30, 1998 Abstract: This invention relates to glutamine:fructose-6-phosphate amidotransferase, or its partial peptide or a salt thereof; a DNA coding for the protein; a recombinant vector; a transformant; a method for producing the protein; a pharmaceutical composition comprising the protein, its partial peptide or a salt thereof; and an antibody against the protein or its partial peptide. The protein, its partial peptide or a salt thereof, and the DNA are useful for a prophylactic or therapeutic agent for hypoglycemia. The antibody can be used in the assay of the protein, its partial peptide or a salt thereof. The protein, its partial peptide or a salt thereof is useful as a reagent for the screening for candidate medical compounds. Excerpt(s): The present invention relates to a novel protein showing an activity of glutamine:fructose-6-phosphate amidotransferase (hereinafter briefly referred to as GFAT), etc. and to a DNA coding for the protein. In recent years, the diabetic population has increased steadily and diabetes is attracting attention as one of adult diseases. Noninsulin-dependent diabetes mellitus (NIDDM) is a type of diabetes frequently found in Japan and its early detection and timely treatment are necessary to prevent the disease. Although the factors causative of NIDDM have not been fully elucidated, recent advances have provided important new insights into this process. It is now well established that abnormalities in insulin sensitive mechanisms and reduced secretion of insulin are causes of insufficient insulin activity in NIDDM. In Europe and America, insulin resistance is predominant in patients with NIDDM while, in Japan, insulin hyposecretion is often the major cause. With recent advances in molecular biology, the cellular and molecular mechanisms underlying insulin resistance such as the insulin receptor structure and the mechanism of signal transduction downstream of the receptor, have been investigated in detail. During the last decade, glucose transporter genes has been cloned and the relationship between mutations in the genes and the process of diabetes has been studied. However, the insulin, glucokinase and mitochondrial gene abnormalities so far elucidated, taken together, account for not more than 1% of NIDDM cases. Other gene abnormalities are to be revealed in the future. Web site: http://www.delphion.com/details?pn=US06207431__
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Hypoglycemic thiazolidinediones and intermediates Inventor(s): Clark; David A. (East Lyme, CT) Assignee(s): Pfizer Inc. (New York, NY) Patent Number: 6,329,408 Date filed: June 1, 1995 Abstract: Optically pure thiazolidinedione alcohols and ethers, and synthetic intermediates for preparing said alcohols and ethers. These compounds have utility as hypoglycemic and hypocholesterolemic agents.
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Excerpt(s): The present invention relates to certain compounds of formulas I, II and IV, depicted below, having utility as hypoglycemic and hypocholesterolemic agents, methods for their use and pharmaceutical compositions containing them. In spite of the early discovery of insulin and its subsequent wide-spread use in the treatment of diabetes, and the later discovery and use of sulfonylureas (e.g. chlorpropamide, tolbutamide, acetohexamide, tolazamide) and biguanides (e.g. phenformin) as oral hypoglycemic agents, the treatment of diabetes remains less than satisfactory. The use of insulin, necessary in about 10% of diabetic patients in which synthetic hypoglycemic agents are not effective (Type I diabetes, insulin dependent diabetes mellitus), requires multiple daily doses, usually by self injection. Determination of the proper dosage of insulin requires frequent estimations of the sugar in the urine or in the blood. The administration of an excess dose of insulin causes hypoglycemia, with effects ranging from mild abnormalities in blood glucose or coma, or even death. Treatment of noninsulin dependent diabetes mellitus (Type II diabetes) usually consists of a combination of diet, exercise, oral agents, e.g., sulfonylureas, and in more severe cases, insulin. However, the clinically available hypoglycemics are unfortunately fraught with other toxic manifestations which limit their use. In any event, where one of these agents may fail in an individual case, another may succeed. A continuing need for hypoglycemic agents, which may be less toxic or succeed where others fail, is clearly evident. Furthermore, atherosclerosis, a disease of the arteries, is recognized to be the leading cause of death in the United States and Western Europe. The pathological sequence leading to atherosclerosis and occlusive heart disease has been described in detail by Ross and Glomset in New England Journal of Medicine 295, 369-377 (1976). The earliest stage in this sequence is the formation of "fatty streaks" in the carotid, coronary and cerebral arteries and in the aorta. These lesions are yellow in color due to the presence of lipid deposits found principally within smooth-muscle cells and in macrophages of the intima layer of the arteries and aorta. Cholesterol and cholesteryl ester account for most of this lipid. Further, it is postulated that most of the cholesterol found within the fatty streaks results from uptake from the plasma. These fatty streaks, in turn, give rise to development of the "fibrous plaque", which consists of accumulated intimal smooth muscle cells laden with lipid and surrounded by extra cellular lipid, collagen, elastin and proteoglycans. The cells plus matrix form a fibrous cap that covers a deeper deposit of cell debris and more extracellular lipid. The lipid is primarily free and esterified cholesterol. The fibrous plaque forms slowly, and Is likely in time to become calcified and necrotic, advancing to the "complicated lesion" which accounts for the arterial occlusion and tendency toward mural thrombosis and arterial muscular spasm that characterize advanced atherosclerosis. Web site: http://www.delphion.com/details?pn=US06329408__ •
Metabolic intervention with GLP-1 or its biologically active analogues to improve the function of the ischemic and reperfused brain Inventor(s): Coolidge; Thomas R. (Falls Village, CT), Ehlers; Mario R. W. (Lincoln, NE) Assignee(s): Bionebraska, Inc. (Lincoln, NE) Patent Number: 6,429,197 Date filed: April 30, 1999 Abstract: It has now been discovered that GLP-1 treatment after acute stroke or hemorrhage, preferably intravenous administration, can be an ideal treatment because it provides a means for optimizing insulin secretion, increasing brain anabolism,
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enhancing insulin effectiveness by suppressing glucagon, and maintaining euglycemia or mild hypoglycemia with no risk of severe hypoglycemia. Excerpt(s): This invention relates to an/effective treatment to improve the function of the ischemic and reperfused brain. Strokes, or cerebrovascular accidents, are the result of an acute obstruction of cerebral blood flow to a region of the brain. There are approximately 500,000 cases each year in the United States, of which 30% are fatal, and hence stroke is the third leading cause of death in the United States. Approximately 80% of strokes are "ischemic" and result from an acute occlusion of a cerebral artery (usually a clot or thrombus), with resultant reduction in blood flow. The remainder are "hemorrhagic", which are due to rupture of a cerebral artery with hemorrhage into brain tissue and consequent obstruction of blood flow due to local tissue compression, creating ischemia. Stroke commonly affects individuals older than 65 years, and the most powerful risk factor is hypertension. However, there are additional strong risk factors, of which the most important is diabetes mellitus, which confers a two to threefold increased risk and is associated with increased mortality and morbidity after stroke. Moreover, there is strong evidence that hyperglycemia per se, whether associated with diabetes or not, correlates with increased stroke-related mortality and morbidity, although the causal relationship and underlying mechanisms remain controversial. Web site: http://www.delphion.com/details?pn=US06429197__ •
Method and apparatus for noninvasive quantitative measurement of blood analytes Inventor(s): Honigs; David E. (Hagerstown, MD), Rosenthal; Robert D. (Montgomery Village, MD) Assignee(s): Futrex Inc. (Gaithersburg, MD) Patent Number: 6,151,517 Date filed: January 22, 1999 Abstract: A method and apparatus for performing quantitative noninvasive measurement of blood analytes, includes correction for measurement interference caused by pulse beat and changing body chemistry associated with blood circulation through the part of the body being measured as a function of time. A hypoglycemia monitor and alarm is provided which takes advantage of the methods described for separating pulse beat information from the measurement signals. Excerpt(s): This invention relates to instruments for the non-invasive quantitative and semi-quantitative measurement of constituents in blood, such as blood glucose levels. Specifically, this invention relates to an improved analysis instrument for measurement of the near-infrared energy absorption of a body part, typically a finger, which is being irradiated with near-infrared energy for measurement of the blood analyte levels. Information concerning the chemical composition of blood is widely used to assess the health characteristics of both people and animals. For example, analysis of the glucose content of blood provides an indication of the current status of metabolism. Blood analysis, by the detection of above or below normal levels of various substances, also provides a direct indication of the presence of certain types of diseases and dysfunctions. In particular, the noninvasive near-infrared quantitative measurement apparatus has particular application for use by diabetics in monitoring the level of glucose in the blood. U.S. Pat. No. 5,028,787, incorporated by reference herein, teaches the use of near-infrared (NIR) analysis techniques in which NIR radiant energy at bandwidths centering on one or more wavelengths of interest is passed through the skin
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of a subject. A portion of the energy re-emerges from the subject and is detected by a detector. The detector generates an output signal which is processed in accordance with NIR quantitative analysis algorithms to determine the concentration of selected blood analytes in the subject. The calculated concentration is then displayed on a display device provided on the instrument. Web site: http://www.delphion.com/details?pn=US06151517__ •
Nutrient composition for exercise Inventor(s): Decombaz; Jacques (Lausanne, CH), Milon; Hubert (Cugy, CH) Assignee(s): Nestec S.A. (Vevey, CH) Patent Number: 6,488,955 Date filed: July 30, 1998 Abstract: A method of maintaining raised blood glucose levels in a mammal during excise, preventing or delaying the onset of hypoglycemia during excise. The method includes step of orally administering to the mammal a nutrient composition containing a carbohydrate source and at least 9% by weight beta-glucan. Excerpt(s): This application is a 371 of PCT/EP97/00448, filed Jan. 27, 1997, which claims the foreign priority of EP 96200301.8, filed Feb. 9, 1996. This invention relates to a nutrient composition which may be used to maintain raised blood glucose levels for extended periods during exercise and which reduces acid reflux symptoms. The invention also relates to methods of maintaining raised blood glucose levels for extended periods, methods for the prevention of hypoglycaemia, methods for increasing exercise performance and methods for reducing acid reflux symptoms; especially in athletes. Humans, during exercise, obtain the energy necessary for the exercise predominantly from two sources; carbohydrates and lipids. However, the rate at which energy is supplied to muscles through carbohydrates is 3 to 4 times higher than for lipids: making carbohydrates an extremely important source of energy for athletes. Web site: http://www.delphion.com/details?pn=US06488955__
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Oxyiminoalkanoic acid derivatives with hypoglycemic and hypolipidemic activity Inventor(s): Imoto; Hiroshi (Kusatsu, JP), Kimura; Hiroyuki (Sakai, JP), Momose; Yu (Takarazuka, JP), Odaka; Hiroyuki (Kobe, JP), Sakamoto; Junichi (Toyonaka, JP) Assignee(s): Takeda Chemical Industries, Ltd. (Osaka, JP) Patent Number: 6,251,926 Date filed: November 15, 1999 Abstract: This invention provides a novel oxyiminoalkanoic acid derivative which has excellent hypoglycemic and hypolipidemic actions and which is used for the treatment of diabetes mellitus, hyperlipemia, insulin insensitivity, insulin resistance and impaired glucose tolerance. Excerpt(s): This application is a 371 of PCT/JP99/02407 filed May, 10, 1999. The present invention relates to novel oxyiminoalkanoic acid derivatives having hypoglycemic effect and hypolipidemic effect, a novel pharmaceutical composition and retinoidrelated receptor function adjuster comprising an oxyiminoalkanoic acid. Such novel
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oxyiminoalkanoic acid derivatives, pharmaceutical compositions and retinoid-related receptor function adjusters are useful as an agent for prevention and/or treatment of diabetes mellitus, hyperlipemia, impaired glucose tolerance, inflammatory disease, arteriosclerosis and the like. Examples of known oxyiminoalkanoic acid derivatives are the intermediates used in the production of.beta.-lactam compounds (Japanese Patent Application KOKAI No.49382/1983, 167576/1984, 77391/1987, 192387/1987, 47186/1991) and a compound having a leukotriene biosynthesis inhibiting effect (e.g., WO96/02507). Web site: http://www.delphion.com/details?pn=US06251926__ •
Polypeptide of protein P140 and DNAs encoding it Inventor(s): Kitagawa; Koichiro (Osaka, JP), Ohno; Hiroyuki (Osaka, JP), Tajima; Hisao (Osaka, JP) Assignee(s): Ono Pharmaceutical Co., Ltd. (Osaka, JP) Patent Number: 6,303,320 Date filed: January 8, 1998 Abstract: The present invention is related to a novel protein p140 polypeptide which is a key protein involved in the signal transmission system of insulin; method for preparation of it; DNA encoding the polypeptide; vector derived with the DNA; host cells transformed with the vector; antibody of the polypeptide; pharmaceutical composition containing the peptide or antibody; method for the prevention and/or treatment of diabetes, which is characterized by tyrosine phosphorylation of the protein p140; agent for the prevention and/or treatment of diabetes, which is characterized by containing a compound which can tyrosine phosphorylate protein p140, as active ingredient and the screening methods of the prevention and/or treatment agent. Tyrosine phosphorylation of protein p140 is an essential step in the induction of hypoglycemia by glucose uptake. Method and agent of prevention and/or treatment based on tyrosine phosphorylation of protein p140 in the present invention not only improve the diabetes-derived hyperglycemic conditions but are also useful for the treatment and/or prevention of diabetes, especially non-insulin dependent diabetes mellitus (NIDDM). Excerpt(s): Priority is claimed under 35 USC 1198 to Japanese patent application Hei-5315806, filed Nov. 24, 1993. The present invention is related to a novel protein p140 polypeptide which is a key protein involved in the signal transmission system of insulin; method for preparation of it; DNA encoding the said polypeptide; vector derived the said DNA; host cells transformed the said vector; antibody of the said polypeptideb pharmaceutical composition containing the said peptide or antibody; method for the prevention and/or treatment of diabetes, which is characterized by tyrosine phosphorylation of the said protein p140 (to be quoted henceforth as phosphorylation in the present detailed specification); agent for the prevention and/or treatment for the currently said the prevention and/or treatment method; agent for the prevention and/or treatment of diabetes, which is characterized by containing a compound which can tyrosine phosphorylate of protein p140, as active ingredient and the screening methods of the said prevention and/or treatment agent. Diabetes, an abnormal metabolic disease, is induced by a defect in the mechanism of glucose metabolism. Web site: http://www.delphion.com/details?pn=US06303320__
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Raising blood sugar level in hypoglycemic mammals by administering inhibitors of dipeptidyl peptidase IV Inventor(s): Demuth; Hans-Ulrich (Halle/Saale, DE), Hoffmann; Torsten (Halle/Saale, DE), Kuhn-Wache; Kerstin (Halle/Saale, DE), Rosche; Fred (Halle/Saale, DE) Assignee(s): Probiodrug (Halle, DE) Patent Number: 6,319,893 Date filed: August 2, 1999 Abstract: A method of raising the blood sugar level in a mammal having hypoglycemia is described. The method reduces degradation of glucagon by administering to the mammal a therapeutically effective amount of an inhibitor of dipeptidyl peptidase IV and physiologically acceptable adjuvants and/or excipients. Excerpt(s): The invention relates to a method in which, by reducing dipeptidyl peptidase IV (DP IV) or DP IV-analogous enzyme activity in the blood of a mammal by administration of activity-reducing effectors, the endogenous (or additionally exogenously administered) glycogenolytically active peptide glucagon or analogues thereof is/are degraded to a reduced extent by DP IV and DP IV-like enzymes, thereby reducing or delaying the decrease in concentration of that peptide hormone or analogues thereof. Owing to that increased stability of (endogenous or exogenously administered) glucagon and its analogues brought about by the action of DP IV effectors, thereby making them available in greater number for the glycogenolytic stimulation of the glucagon receptors of, in particular, liver cells, the duration of activity of the body's own glucagon changes, consequently resulting in stimulation of the catabolic carbohydrate metabolism of the organism treated. As a result, the blood sugar level in the serum of the treated organism rises above the glucose concentration characteristic of hypoglycaemia. Thereby, metabolic anomalies, such as hypoglycaemic states resulting from reduced glucose concentrations in the blood, can be prevented or alleviated. Web site: http://www.delphion.com/details?pn=US06319893__
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Substituted quinazolines and analogs and use thereof Inventor(s): Cai; Sui X. (San Diego, CA), Fick; David B. (Newport Beach, CA), Field; George (Danville, CA), Lan; Nancy C. (S. Pasadena, CA), Upasani; Ravi (San Jose, CA), Wang; Yan (San Diego, CA) Assignee(s): Euro-Celtique S.A. (Luxembourg, LU) Patent Number: 6,465,472 Date filed: September 1, 2000 Abstract: The invention relates to novel quinazolines and heterocycles which are antagonists or positive modulators of AMPA receptors, and the use thereof for treating, preventing or ameliorating neuronal loss associated with stroke, global and focal ischemia, CNS trauma, hypoglycemia and surgery, as well as treating or ameliorating neurodegenerative diseases including Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's disease, Parkinson's disease and Down's syndrome, treating, preventing or ameliorating the adverse consequences of the overstimulation of the excitatory amino acids, treating, preventing or ameliorating anxiety, psychosis, convulsions, chronic pain, glaucoma, retinitis, urinary incontinence, muscular spasm and inducing anesthesia, as
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well as for treating or ameliorating the adverse consequences of excitatory amino acid deficiency such as schizophrenia, myoclonus. Alzheimer's disease and malnutrition and neural maldevelopment, and as cognition and learning enhancers. Excerpt(s): This invention is in the field of medicinal chemistry. In particular, the invention is related to novel substituted quinazolines and analogs thereof. These compounds are antagonists of.alpha.-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) ionotropic receptors. Certain of these compounds are positive modulators of AMPA receptors. The invention also is directed to the use of novel substituted quinazolines and analogs thereof for the treatment of neuronal damage following global and focal ischemia, and for the treatment or prevention of neurodegenerative conditions as anticonlvulsants, as cognitive enhancers, and for the treatment of schizophrenia, Parkinson's disease and myoclonus. The compounds of the invention are also useful for treatment or prevention of pain, including acute and chronic pain. The invention also is directed to a process for the preparation of the substituted quinazolines and analogs thereof. Excitatory amino acid receptors are classified into two general types. Receptors that are directly coupled to the opening of cation channels in the cell membrane of the neurons are termed "ionotropic." This type of receptor has been subdivided into at least three subtypes, which are defined by the depolarizing actions of the selective agonist Nmethyl-D-aspartate (NMDA),.alpha.-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA), and kainic acid (KA). The second general type is the G-protein or second messenger-linked "metabotropic" excitatory amino acid receptor. This second type, when activated by the agonists quisqualate, ibotenate, or trans-1-aminocyclopentane1,3-dicarboxylic acid, leads to enhanced phosphoinositide hydrolysis in the postsynaptic cell. Both types of receptors appear not only to mediate normal synaptic connections during development, but also change in the efficiency of synaptic transmission throughout life. (Schoepp, Bockaert, and Sladeczek, Trends Pharm. Sci. 11:508 (1990); McDonald and Johnson, Brain Res. Rev. 15:41 (1990)). The excessive or inappropriate stimulation of excitatory amino acid receptors leads to neuronal cell damage or loss by a mechanism known as excitotoxicity. The medical consequences of such neuronal degeneration makes the abatement of these degenerative neurological processes an important therapeutic goal. (See U.S. Pat. No. 5,284,957). Antagonists of the AMPA receptor are considered useful in treating, preventing and ameliorating a number of neurologic disorders which are due to overstimulation by the excitatory amino acids. These include acute neurologic disorders such as domoic acid poisoning; cerebral ischemia, global ischemia associated with cardiac arrest; stroke; spinal cord trauma; hypoxia; anoxia; poisoning be carbon monoxide, manganese or cyanide; hypoglycemia; mechanical trauma to the nervous system; epileptic seizures; and chronic neurologic disorders such as Huntington's disease, neuronal injury associated with HIV and AIDS, AIDS dementia, neuropathic pain syndrome, olivopontocerebral atrophy, Parkinson's disease, amyotrophic lateral sclerosis, mitochondrial abnormalities, Alzheimer's disease, hepatic encephalopathy, Tourette's syndrome, drug addiction and urinary incontinence (see Lipton and Rosenberg, N. Engl. J. Med. 330: 613-622 (1994)) and treatment or amelioration of a number of chronic neurologic disorders such as schizophrenia. AMPA receptor antagonists are also useful in treating, preventing and ameliorating acute and chronic pain, pain associated with post-therapeutic neurolgia, insterstital cystitis, osteoarthritis, spinal cord injury, cancer and diabetic neuropathy. Web site: http://www.delphion.com/details?pn=US06465472__
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Sulfonylurea receptor trangenic rodents Inventor(s): Bryan; Joseph (Houston, TX), Bryan; Lydia Aguilar (Houston, TX), Nelson; Daniel (Charlotte, NC) Assignee(s): Baylor College Of Medicine (Houston, TX) Patent Number: 6,031,150 Date filed: June 7, 1995 Abstract: The present invention is directed to a method of detecting persistent hyperinsulinemic hypoglycemia of infancy comprising obtaining a sample comprising patient nucleic acids from a patient tissue sample; amplifying sulfonylurea receptor specific nucleic acids from said patient nucleic acids to produce a test fragment; obtaining a sample comprising control nucleic acids from a control tissue sample; amplifying control nucleic acids encoding wild type sulfonylurea receptor to produce a control fragment; comparing the test fragment with the control fragment to detect the presence of a sequence difference in the test fragment, wherein a difference in said test fragment indicates persistent hyperinsulinemic hypoglycemia of infancy. A diagnostic kit and primers for the detection of persistent hyperinsulinemic hypoglycemia of infancy are also within the scope of the present invention. Excerpt(s): Sulfonylureas are oral hypoglycemics widely used in the treatment of NonInsulin Dependent Diabetes Mellitus (NIDDM). They enter the bloodstream, bind with high affinity to a pancreatic.beta.-cell plasma membrane protein termed the sulfonylurea receptor, and stimulate insulin release. The mechanism of stimulation is thought to be through inhibition of an ATP-sensitive K+ channel (K.sub.ATP), a key protein which sets the.beta.-cell resting membrane potential (Ashcroft, et al. Cell. Signal. 1990, 2, 197214, all references cited herein are incorporated by reference in their entirety). A reduction in potassium outflow causes depolarization of the plasma membrane, activation of L-type voltage-dependent calcium channels (VDCCs), and increased cytosolic calcium. This triggers insulin release by as yet unknown mechanisms (Rajan, et al. Diabetes Care 1990, 13, 340-363). In NIDDM patients on sulfonylureas, the consequent reduction in blood glucose to more normal levels is thought to be critical in controlling the disease (Gerich, J. E. New Engl. J. Med. 1989, 321, 1231-1245). The biochemistry of the sulfonylurea receptor (SUR) (Ashcroft et al Biochem. Biophys Acta 1992, 1175, 45-49 and Panten et al. Horm. Metab. Res. 1992, 24, 549-554) is consistent with the electrophysiology of the.beta.-cell K.sub.ATP channel. The endogenous regulators of channel activity include cytosolic nucleotides (ATP and Mg-ADP) and possibly phosphorylation. In the absence of cytosolic nucleotides, sulfonylureas weakly inhibit channel activity (Schwanstecher et al. Br. J. Pharmacol 1992, 107, 87-94). When channels are activated by Mg-ADP, inhibition by ATP is strongly promoted by the presence of sulfonylureas. These results are interpreted as evidence that simultaneous occupancy of two nucleotide binding sites is required for effective channel inhibition by the sulfonylureas. The reported allosteric interactions correlate well with evidence that the brain receptor has two nucleotide binding sites (de Weille, et al. J. Biol. Chem 1992, 267, 4557-4563) physically located on the same polypeptide chain as the sulfonylurea binding site (Bernardi et al. Biochemistry 1992, 31, 6328-6332). One binding site appears to be specific for ATP, and is proposed to be the same site at which micromolar concentrations of ATP inhibit the K.sub.ATP channel. A second site has high affinity for Mg-ADP, with occupancy at this site promoting channel opening. Absolute concentrations of ATP and ADP in the cell are thought to regulate channel activity in a straightforward fashion (Hopkins et al. J. Membrane Biol. 1992, 129, 287-295). High ATP concentrations as a result of high serum glucose levels close the channel, stimulating
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insulin secretion. Reduced glucose levels increase intracellular ADP concentrations, and thereby increase the open channel probability, and decrease insulin secretion. Although sulfonylureas, particularly tolbutamide and more potent second generation drugs like glyburide and glipizide, are considered to be relatively specific inhibitors of the K.sub.ATP channel, the exact relationship between the sulfonylurea receptor and the K.sub.ATP channel is not clear (Nichols et al. Am. J. Physiol. 1991, 261, H1675-H1686, Takano et al. Progress in Neurobiology 1993, 41, 21-30, and Edwards et al. Annu. Rev. Pharmacol. Toxicol. 1993, 33, 597-637). In the insulin-secreting CRI-G1 cell line, the addition of glyburide, or tolbutamide to inside-out plasma membrane patches inhibits the K.sub.ATP channel (Khan et al. Proc. R. Soc. Lond. B. 1993, 253, 225-231), intimating direct interactions between sulfonylureas and the channel protein. In another insulin secreting cell line, CRI-D11 cells, however, the loss of sulfonylurea binding sites with the retention of K.sub.ATP activity suggests these two activities may uncouple and reside on separate, transiently bound subunits (Khan et al. Proc. R. Soc. Lond. B. 1993, 253, 225231). Similarly, in other cell and tissue types, sulfonylurea binding and channel activity may be uncoupled (Ashford et al Br. J. Pharmac. 1990, 101, 531-540). A technique is not currently available to assess whether K.sub.ATP activity resides within the same polypeptide containing the putative nucleotide and sulfonylurea binding sites, or on separate loosely, or tightly bound subunits. Web site: http://www.delphion.com/details?pn=US06031150__ •
Supportive therapy for diabetes, hyperglycemia and hypoglycemia Inventor(s): Cherukuri; Reddy Sastry V. (El Dorado Hills, CA), Cheruvanky; Rukmini (Folsom, CA), McPeak; Patricia (El Dorado Hills, CA) Assignee(s): The RiceX Company (El Dorado Hills, CA) Patent Number: 6,303,586 Date filed: August 28, 1998 Abstract: Methods for controlling serum glucose level in a mammal comprising ingesting a stabilized rice bran derivative selected from the group consisting of a solubilized fraction, an insolubilized fraction, an enzyme treated stabilized rice bran and mixtures thereof, thereby reducing serum glucose level in said mammal. Excerpt(s): The present invention relates to methods for controlling serum glucose levels in mammals. Diabetes is a chronic disease that has no cure. It affects 16 million people in the U.S. and more than 125 million people worldwide. Diabetes is the fourth-leading cause of death by disease in the United States. In 1997, more than 178,000 people died from the disease and its relates complications. Diabetes mellitus is characterized by an impaired ability to metabolize carbohydrates, increased glucose in the blood, and excretion of glucose in the urine. This defect involves interference with insulin in its role of facilitating uptake of glucose by cells, to give energy as ATP. Web site: http://www.delphion.com/details?pn=US06303586__
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System and method for monitoring and controlling the glycemic state of a patient Inventor(s): Houben; Richard (Berg en Terblijt, NL), Larik; Vincent (Kerkrade, NL) Assignee(s): Medtronic, Inc. (Minneapolis, MN) Patent Number: 6,572,542 Date filed: March 3, 2000 Abstract: Information derived from ECG signals and EEG signals may be employed in combination to reliably predict the onset, or to indicate the presence of, hypoglycemia in a human patient. In one embodiment, ECG and EEG signals are processed and the information derived from them is combined to determine whether a patient suffering from diabetes is undergoing a hypoglycemic event, or whether such an event is imminent. Input data from the patient or a health care provider may also be used to increase the accuracy and reliability of the system. Detection of a hypoglycemic event by the system can result in the output of an alarm signal and/or the delivery or administration of a beneficial agent such as insulin, glucagon or diazoxide to the patient. The system may be implantable, external, or a combination of external and implantable components. The control strategy of the present system is preferably microprocessor based and/or implemented using dedicated electronics. In another embodiment, the glycemic state of the patient is continuously or relatively continuously monitored and controlled by the system. The system may contain any of a number of different types of feedback control systems for monitoring the glycemic state of a patient and controlling same, such as fuzzy logic systems, adaptive systems, reinforcement learning systems, and the like. Excerpt(s): This application relates to a system and method for monitoring and/or controlling patient diabetes-related blood constituents. From this total, 10% (or about 0.8 million persons) are estimated to be insulin dependent diabetes mellitus (IDDM) patients. The Diabetes Control and Complications Trial (the DCCT) showed a 70% reduction in complications resulting from tight metabolic control in IDDM patients. See "The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus", The Diabetes Control and Complications Trial Research Group, The New England Journal of Medicine, Vol. 329, No 14. Sep. 30, 1993. The DCCT underscores the importance of developing a better way to control blood glucose for the IDDM patient group. Unfortunately, the study showed substantial evidence that the frequency of hypoglycemic excursions increases 23 times in IDDM patients subjected to tight metabolic control compared to regular treatment. Frequent hypoglycemic excursions additionally create hypoglycemic unawareness, a state where patients become incapable of recognizing themselves the usual symptoms associated with hypoglycemia. In the U.S. diabetes mellitus (DM) population, 90% (or 7 million persons) are estimated to be non-insulin dependent diabetes mellitus (NIDDM) patients. NIDDM patients may be subdivided into insulin users (30%, or 2.3 million persons), of which at least 25% (or 0.52 million persons) measures their blood glucose levels on a daily basis. The percentage of NIDDM patients receiving insulin treatment increases with the duration of NIDDM from 25% (0-4 years) to 60% (>20 years). It is estimated that the diagnosed number of NIDDM patients reflects only about 50% of the actual population suffering from NIDDM. However, it is recognized that only a limited percentage of this group requires improved treatment. The remainder of the NIDDM population generally self manages the disease though careful meal planning and exercise, or by means of oral hypoglycemic agents. Web site: http://www.delphion.com/details?pn=US06572542__
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Therapeutic food composition and method to diminish blood sugar fluctuations Inventor(s): Kaufman; Francine (Los Angeles, CA) Assignee(s): Childrens Hospital Los Angeles (Los Angeles, CA) Patent Number: 6,339,076 Date filed: August 4, 1998 Abstract: A therapeutic food composition for treatment of diabetic patients to diminish fluctuations in blood sugar levels and prevent hypoglycemic episodes, comprising per unit about 20-50 grams of nutrients including slowly absorbed or digested complex carbohydrate, preferably uncooked cornstarch; more rapidly absorbed complex carbohydrate; protein; fat; and at least one sweetening agent, but less than about 3 grams of any simple sugar other than fructose. Fructose may be present in the composition in quantities greater than 3 grams per unit. Diabetic patients may be treated to diminish blood sugar fluctuations and prevent hypoglycemia via the administration of the novel food composition as an evening or pre-bedtime snack-or during the daytime hours to patients receiving insulin therapy or engaging in activities that might provoke hypoglycemia. Excerpt(s): This invention relates to therapeutic treatments of diabetes mellitus. More particularly, this invention relates to treatment methods and compositions for the prevention of severe fluctuations in blood sugar levels in diabetic patients. Symptoms of hypoglycemia fall into two main categories. Rapid epinephrine release causes sweating, tremor, tachycardia, anxiety, and hunger. Central nervous system symptoms include dizziness, headache, clouding of vision, blunted mental acuity, confusion, abnormal behavior, convulsions and loss of consciousness. When hypoglycemia is recurrent or severe, nervous system symptoms predominate, and the epinephrine phase may not be recognizable. With more rapid drops or wide swings in plasma glucose (as in insulin reactions), adrenergic symptoms are prominent (Harrison's Principles of Internal Medicine, 11th Ed., McGraw-Hill Book Company, New York, 1987, p. 1800). Numerous strategies have been developed to achieve the goal of maintaining blood glucose at a relatively constant level in diabetic patients, such as open looped continuous subcutaneous insulin pumps and multiple daily injections of insulin. These intensive insulin regimens are coupled with home glucose monitoring, and many patients measure their blood glucose levels by finger prick up to 6 to 8 times per day to assure that close to normal blood sugar levels are maintained. This regimen is prescribed because studies have shown that by avoiding excessive high blood sugar levels, the long-term outcome of patients with diabetes can be improved. However, this regimen, which decreases episodes of high blood sugar, also causes patients to experience more low blood sugar reactions (hypoglycemia). Web site: http://www.delphion.com/details?pn=US06339076__
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Tri-and tetra-substituted guanidines and their use as excitatory amino acid antagonists Inventor(s): Keana; John F. W. (Eugene, OR), Weber; Eckard (Laguna Beach, CA) Assignee(s): State of Oregon, acting by and through the Oregon State Board of Higher (Eugene, OR) Patent Number: 6,251,948 Date filed: June 6, 1995
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Abstract: Tri- and tetra-substituted guanidines which exhibit a high binding affinity to phencyclidine (PCP) receptors and, more preferably, low affinity to the brain sigma receptors. These guanidine derivatives act as non-competitive inhibitors of glutamate induced responses of the NMDA receptor by acting as blockers for the ion channel of the NMDA receptor-ion channel complex. These compounds thus exert neuroprotective activity and are useful in the therapeutic treatment of neuronal loss in hypoxia, hypoglycemia, brain or spinal cord ischemia, and brain or spinal chord trauma as well as being useful for the treatment of epilepsy, Alzheimer's disease, Amyotrophic Lateral Sclerosis, Parkinson's disease, Huntington's disease, Down's Syndrome, Korsakoff's disease and other neurodegenerative disorders. Excerpt(s): This invention relates to tri- and tetra-substituted guanidines, and to pharmaceutical compositions comprising the same, which possess neuroprotective capability. This invention further relates to methods involving the use of these compounds as excitatory amino acid antagonists, e.g., for treating diseases of the nervous system in which the pathophysiology of the disease involves excessive excitation of nerve cells by agonists of the glutamate/N-methyl-d-aspartate (NMDA) receptor. Such excessive excitation can lead to dysfunction of the nervous system in the case of epilepsy and to nerve cell degeneration in cases of hypoxia, hypoglycemia, brain or spinal chord ischemia, brain or spinal chord trauma and in neurodegenerative diseases such as Parkinson's disease, Huntington's disease, Amyotrophic Lateral Sclerosis (ALS), Alzheimer's disease, Down's Syndrome and Korsakoff's disease. U.S. Pat. No. 4,471,137 discloses N,N,N'N"-tetraalkyl guanidines as being sterically hindered bases useful in chemical synthesis. U.S. Pat. No. 4,709,094 discloses 1,3-disubstitutedguanidines, e.g., 1,3-dibutyl-guanidine and 1,3 di-o-tolyl-guanidine, as sigma brain receptor ligands. Web site: http://www.delphion.com/details?pn=US06251948__ •
Use of human transferrin in controlling insulin levels Inventor(s): Faerman; Carlos H. (Ithaca, NY), Karplus; P. Andrew (Ithaca, NY), Vargas; Luis A. (Santiago, CL) Assignee(s): Cornell Research Foundation, Inc. (Ithaca, NY) Patent Number: 6,069,193 Date filed: October 7, 1998 Abstract: The present invention relates to the use of transferrin in controlling insulin levels. Transferrin can disrupt insulin:receptor interactions in mammalian cells, may be used in mammals to treat hypoglycemia, may also be used to inhibit production of insulin by mammalian cells, and can decrease the serum insulin levels in a mammal. The invention further provides methods for identifying compounds which modulate the effect of transferrin on insulin signal transduction. Pharmaceutical compositions containing transferrin are also disclosed. Excerpt(s): The present invention relates to the use of human transferrin in controlling insulin levels. Diabetes mellitus is the most common of the serious metabolic diseases affecting humans. It has been estimated that there are over 200 million diabetics in the world. (See J. Steinke and J. S. Soeldner, Diabetes Mellitus in Principles of Internal Medicine, 8th ed., 563 (1977). Diabetics not only face a decreased life expectancy but also the ever-present possibility of disabling complications. Metabolically, diabetes is characterized by an inappropriate elevation of blood glucose levels. In type I Diabetes
Patents 161
Mellitus, this is due to an absence of insulin in the individual. In type II Diabetes Mellitus, although there is circulating insulin, its signal is not efficiently transduced via the insulin receptor, giving rise to insulin resistance, where the body responds less and less well to a given amount of insulin. Insulin is a peptide hormone which is produced by the Langerhans islets in the pancreas. Insulin triggers increased glucose utilization, protein synthesis, and the formation and storage of neutral lipids. The present invention focuses on Type II diabetes mellitus or non-insulin-dependent diabetes. Web site: http://www.delphion.com/details?pn=US06069193__
Patent Applications on Hypoglycemia As of December 2000, U.S. patent applications are open to public viewing.10 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to hypoglycemia: •
1-(ARYLOXY)PROPIONOYL-2-ARYLSULFONYL HYDRAZINES, PROCESS FOR PREPARATION THEREOF AND USE THEREOF AS HYPOGLYCEMIC AGENTS Inventor(s): Diwan, Prakash Vamanrao; (Hyderabad, IN), Nageswar Yadavalli, Venkata Durga; (Hyderabad, IN), Raghavan, Kondapuram Vijaya; (Hyderabad, IN), Rao, Adari Bhaskar; (Hyderabad, IN), Sistla, Ramakrishna; (Hyderabad, IN), Thallapalli, Ramalingam; (Hyderabad, IN), Yadav, Jhillu Singh; (Hyderabad, IN) Correspondence: Sughrue Mion, Pllc; 2100 Pennsylvania Avenue, NW; Washington; DC; 20037-3213; US Patent Application Number: 20030187065 Date filed: March 29, 2002 Abstract: The present invention relates to 1-(aryloxy)propionoyl-2-arylsulfonyl hydrazines useful as hypoglycemic agents, and to a process for synthesis thereof. The present invention also relates to the synthesis of 1-(aryloxy)propionoyl-2-arylsulfonyl hydrazines as new hypoglycemic agents which may be useful in the treatment of diabetes. Excerpt(s): The present invention relates to 1-(aryloxy)propionoyl-2-arylsulfon- yl hydrazines useful as hypoglycemic agents, and to a process for synthesis thereof. The present invention also relates to the synthesis of 1-(aryloxy)propionoyl-2-arylsulfonyl hydrazines as new hypoglycemic agents which may be useful in the treatment of diabetes. Introduction of more clinically effective hypoglycemic agents has been followed invariably by6 the rapid emergence of resistant antidiabetic drugs leading to increasing demand for new and potent hypoglycemic drugs. Acquisition of resistance has seriously reduced the therapeutic value of many known drugs including antidiabetics and has become a major stimulus to look for new moieties. Hence, the best approach is to look for new molecules structurally different from the existing drugs. The present invention relates to such an effort in developing title compounds as new hypoglycemic agents. These have not so far been investigated for the hypoglycemic activity and all compounds described are new molecules reported for the first time. Reference may be made to Indian Drugs, 17, 315, 1980, wherein, authors have
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This has been a common practice outside the United States prior to December 2000.
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syhthesized arylsulfonyl hydrazines as hypoglycemic agents. The drawbacks are that no substitutions were made to the hydrazine group which can improve the hppoglycemic activity. Incorporation of aryloxyalkyl substituents to organic moieties has been found to result in compounds which possess enhanced biological profile. Reference may also be made to Indian J. Chem:27B, 1057-1059, 1988, wherein authors have introduced substitutions by condensation of 4-chlorophenoxyacetic and isobutyric acid hydrazides with arylsulfonyl chlorides. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
3,7-dihydro-purine-2,6-dione derivatives as CRF receptor ligands Inventor(s): Hartz, Richard A.; (Kennett Square, PA) Correspondence: Stephen B. Davis; Bristol-myers Squibb Company; Patent Department; P O Box 4000; Princeton; NJ; 08543-4000; US Patent Application Number: 20030119831 Date filed: November 7, 2002 Abstract: Compounds provided herein are 3,7-dihydro-purine-2,6-dione derivatives of Formula (I): 1Such compounds are particularly useful as CRF receptor ligands, and hence, in the treatment of various neurologically-related disorders such as affective disorder, anxiety and depression, headache, irritable bowel syndrome, post-traumatic stress disorder, supranuclear palsy, immune suppression, Alzheimer's disease, gastrointestinal diseases, anorexia nervosa or other feeding disorder, drug addiction, drug or alcohol withdrawal symptoms, inflammatory diseases, cardiovascular or heartrelated diseases, fertility problems, human immunodeficiency virus infections, hemorrhagic stress, obesity, infertility, head and spinal cord traumas, epilepsy, stroke, ulcers, amyotrophic lateral sclerosis or hypoglycemia. Excerpt(s): This application claims the priority benefit of U.S. Provisional Appl No. 60/331,829, filed Nov. 20, 2001, the disclosure of which is incorporated herein by reference in its entirety. This invention relates to 3,7-dihydro-purine-2,6-dione derivatives as CRF antagonists, pharmaceutical compositions containing the same, and methods of using the same in the treatment of psychiatric disorders and neurological diseases including affective disorder, anxiety related disorders, depression, headache, post-traumatic stress disorder, supranuclear palsy, Alzheimer's disease, head and spinal cord traumas, anorexia nervosa or other feeding disorders, as well as treatment of irritable bowel syndrome, gastrointestinal diseases, cardiovascular or heart-related diseases, immune supression, human immunodeficiency virus infections, fertility problems, or a disorder the treatment of which can be effected or facilitated by antagonizing CRF, including but not limited to disorders induced or facilitated by CRF. Corticotropin releasing factor (herein referred to as CRF), a 41 amino acid peptide, is the primary physiological regulator of proopiomelanocortin (POMC)-derived peptide secretion from the anterior pituitary gland [J. Rivier et al., Proc. Nat. Acad. Sci. (USA) 80:4851 (1983); W. Vale et al., Science 213:1394 (1981)]. In addition to its endocrine role at the pituitary gland, immunohistochemical localization of CRF has demonstrated that the hormone has a broad extrahypothalamic distribution in the central nervous system and produces a wide spectrum of autonomic, electrophysiological and behavioral effects consistent with a neurotransmitter or neuromodulator role in brain [W. Vale et al., Rec. Prog. Horm. Res. 39:245 (1983); G. F. Koob, Persp. Behav. Med. 2:39 (1985); E. B. De Souza et al., J. Neurosci. 5:3189 (1985)]. There is also evidence that CRF plays a significant role in integrating the response of the immune system to physiological,
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psychological, and immunological stressors [J. E. Blalock, Physiological Reviews 69:1 (1989); J. E. Morley, Life Sci. 41:527 (1987)]. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
4-Substituted piperidine analogs and their use as subtype selective NMDA receptor, antagonists Inventor(s): Bigge, Christopher F.; (Ann Arbor, MI), Cai, Sui Xiong; (Foothill, CA), Keana, John F.W.; (Eugene, OR), Lan, Nancy F.; (South Pasadena, CA), Weber, Eckard; (Laguna Beach, CA), Woodward, Richard; (Aliso Viejo, CA), Wright, Jonathan; (Ann Arbor, MI), Zhou, Zhang-Lin; (Irvine, CA) Correspondence: Fitzpatrick Cella Harper & Scinto; 30 Rockefeller Plaza; New York; NY; 10112; US Patent Application Number: 20030105133 Date filed: July 29, 2002 Abstract: Novel 4-substituted piperidine analogs, pharmaceutical compositions containing the same and the method of using 4-substituted piperidine analogs as selectively active antagonists of N-methyl-D-aspartate (NMDA) receptor subtypes for treating conditions such as stroke, cerebral ischemia, central nervous system trauma, hypoglycemia, anxiety, convulsions, aminoglycoside antibiotics-induced hearing loss, migraine headaches, glaucoma, CMV retinitis, chronic pain, opioid tolerance or withdrawals, or neurodegenerative disorders, such as lathyrism, Alzheimer's Disease, Parkinsonism and Huntington's Disease are described. Also described are novel methods for preparing 4-substituted piperidine analogs and novel intermediates of the 4-substituted piperidine analogs. Excerpt(s): This invention is related to 4-substituted piperidine analogs, including hydroxypiperidine and tetrahydropyridine analogs, as well as novel intermediates of the 4-substituted analogs. The analogs are selectively active as antagonists of N-methylD-aspartate (NMDA) receptor subtypes. The invention is also directed to the use of 4substituted piperidine analogs as neuroprotective agents for treating conditions such as stroke, cerebral ischemia, central nervous system trauma, hypoglycemia, anxiety, convulsions, aminoglycoside antibiotics-induced hearing loss, migraine headache, chronic pain, glaucoma, CMV retinitis, psychosis, urinary incontinence, opioid tolerance or withdrawal, or neuro-degenerative disorders such as lathyrism, Alzheimer's Disease, Parkinsonism and Huntington's Disease. Excessive excitation by neurotransmitters can cause the degeneration and death of neurons. It is believed that this degeneration is in part mediated by the excitotoxic actions of the excitatory amino acids (EAA) glutamate and aspartate at the N-methyl-D-Aspartate (NMDA) receptor. This excitotoxic action is considered responsible for the loss of neurons in cerebrovascular disorders such as cerebral ischemia or cerebral infarction resulting from a range of conditions, such as thromboembolic or hemorrhagic stroke, cerebral vasospasms, hypoglycemia, cardiac arrest, status epilepticus, perinatal asphyxia, anoxia such as from drowning, pulmonary surgery and cerebral trauma, as well as lathyrism, Alzheimer's Disease, Parkinson's Disease and Huntington's Disease. Ar.sup.1 and Ar.sup.2 are each independently substituted or unsubstituted aryl, a heteroaromatic ring, or a heteroaromatic bicylic ring. The tetrahydropyridines and hydroxypiperidines of this reference are indicated to be useful as central nervous system agents, particularly as dopaminergic, antipsychotic and antihypertensive agents, and for treating central nervous system disorders such as Parkinson Disease, Huntington Disease and depression. The particular 4-substituted
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piperidines, including the 4-hydroxypiperdines and tetrahydropyridines of this invention are not exemplified. In addition, there is no disclosure or suggestion of treating disorders with selective NMDA receptor subtype antagonists and the advantages of such treatment. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Aminoadamantane derivatives as therapeutic agents Inventor(s): Larrick, James W.; (Woodside, CA), Lipton, Stuart A.; (Rancho Santa Fe, CA), Stamler, Jonathan S.; (Chapel Hill, NC), Wang, Yuqiang; (Mountain View, CA), Ye, Wenqing; (Fremont, CA) Correspondence: Mintz, Levin, Cohn, Ferris,; Glovsky & Popeo, P.C.; One Financial Center; Boston; MA; 02111; US Patent Application Number: 20030008889 Date filed: July 19, 2002 Abstract: The present invention provides novel aminoadamantane derivatives, methods of making the derivatives, compositions including the novel aminoadamantane derivatives, and methods for the treatment and prevention of neurological diseases using the derivatives and compositions. There are a variety of neurological disorders that can be treated using the present invention, including, for example, the following: neurological disorders arising from trauma, ischemic or hypoxic conditions that can be treated include stroke, hypoglycemia, cerebral ischemia, cardiac arrest, spinal cord trauma, head trauma, perinatal hypoxia, cardiac arrest and hypoglycemic neuronal damage; neurodegenerative disorders such as epilepsy, Alzheimer's disease, Huntington's disease Parkinsonism, and amyotrophic lateral sclerosis; other diseases or disorders such as convulsion, pain, depression, anxiety, schizophrenia, muscle spasms, migraine headaches, urinary incontinence, nicotine withdrawal, opiate tolerance and withdrawal, emesis, brain edema, tardive dyskinesia, AIDS-induced dementia, ocular damage, retinopathy, cognitive disorders, and neuronal injury associated with HIVinfection such as dysfunction in cognition, movement and sensation. Excerpt(s): Certain adamantane derivatives have been used to treat illnesses. Rimantadine (1-(1-aminoethyl)adamantane) is used for the prophylaxis and treatment of influenza in humans. Amantadine has been used for the treatment of both influenza and Parkinson's disease (Schwab et al., J Am. Med. Assoc. (1969) 208:1168). Another derivative, memantine, is currently under clinical investigation for the treatment of various neurodegenerative diseases and has been licensed for the treatment of Parkinson's associated spasticity in Germany (Schneider et al., Dtsch. Med. Wschr. (1984) 109:987). Memantine protects cortical and retinal neuron cultures from the toxicity of glutamate, NMDA and the HIV-1 coat protein gp120 (Dreyer et al., Science (1990) 248:364). Recent studies demonstrate that it prevents quinolinic acid-induced hippocampal damage in rats (Kelhoff and Wolf., Eur. J. Pharmacol. (1992) 219:451). Memantine demonstrates antiphypoxic properties in vitro and in vivo. It is thought that memantine exerts a neuroprotective effect because it is a micromolar antagonist of the NMDA receptor (Bormann J., Eur. J. Pharmacol. (1989) 166:591). While memantine is being used to treat neurological disorders, the variety and severity of neurological diseases presents a need for other neuroprotective agents. The present invention provides novel compounds, compositions and methods for the treatment of neurological diseases. The present invention also provides methods of making the novel compounds.
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Aminoalkyl substituted 5,6,7,8-tetrahydro-9H-pyridino[2,3-b]indole and tetrahydro-9H-pyrimidino[4,5-b]indole derivatives: CRF1 specific ligands
5,6,7,8-
Inventor(s): Darrow, James W.; (Wallingford, CT), Horvath, Raymond F.; (North Branford, CT), Maynard, George D.; (Clinton, CT) Correspondence: Steven J. Sarussi; Mcdonnell Boehnen Hulbert & Berghoff; 32nd Floor; 300 S. Wacker Drive; Chicago; IL; 60606; US Patent Application Number: 20030105117 Date filed: August 27, 2002 Abstract: Disclosed are compounds of the formula: 1whereinAr, R.sup.1, W, X and m are substituents as defined herein.These compounds are modulators of CRF receptors and are therefore useful for treating affective disorder, anxiety, depression, headache, irritable bowel syndrome, post-traumatic stress disorder, supranuclear palsy, immune suppression, Alzheimer's disease, gastrointestinal diseases, anorexia nervosa or other feeding disorder, drug addiction, drug or alcohol withdrawal symptoms, inflammatory diseases, cardiovascular or heart-related diseases, fertility problems, human immunodeficiency virus infections, hemorrhagic stress, obesity, infertility, head and spinal cord traumas, epilepsy, stroke, ulcers, amyotrophic lateral sclerosis, hypoglycemia or a disorder the treatment of which can be effected or facilitated by antagonizing CRF, including but not limited to disorders induced or facilitated by CRF, in mammals, comprising: administering to the mammal a therapeutically effective amount of a compound of Formula I. Excerpt(s): The present invention relates to aminoalkyl substituted 5,6,7,8-tetrahydro9H-pyridino[2,3-b]indole and 5,6,7,8-tetrahydro-9H-pyrimidino[4,5-b]indole derivatives, pharmaceutical compositions containing such compounds and their use in treating psychiatric disorders, neurological diseases, immunological, cardiovascular or heart-related diseases and colonic hypersensitivity associated with psychopathological disturbance and stress. Corticotropin releasing factor (herein referred to as CRF), a 41 amino acid peptide, is the primary physiological regulator of proopiomelanocortin (POMC) derived peptide secretion from the anterior pituitary gland [J. Rivier et al., Proc. Nat. Acad. Sci. (USA) 80:4851 (1983); W. Vale et al., Science 213:1394 (1981)]. In addition to its endocrine role at the pituitary gland, immunohistochemical localization of CRF has demonstrated that the hormone has a broad extrahypothalamic distribution in the central nervous system and produces a wide spectrum of autonomic, electrophysiological and behavioral effects consistent with a neurotransmitter or neuromodulator role in brain [W. Vale et al., Rec. Prog. Horm. Res. 39:245 (1983); G. F. Koob, Persp. Behav. Med. 2:39 (1985); E. B. De Souza et al., J. Neurosci. 5:3189 (1985)]. There is also evidence that CRF plays a significant role in integrating the response of the immune system to physiological, psychological, and immunological stressors [J. E. Blalock, Physiological Reviews 69:1 (1989); J. E. Morley, Life Sci. 41:527 (1987)]. Clinical data provide evidence that CRF has a role in psychiatric disorders and neurological diseases including depression, anxiety-related disorders and feeding disorders. A role for CRF has also been postulated in the etiology and pathophysiology of Alzheimer's disease, Parkinson's disease, Huntington's disease, progressive supranuclear palsy and amyotrophic lateral sclerosis as they relate to the dysfunction of CRF neurons in the central nervous system [for review see E. B. De Souza, Hosp. Practice 23:59 (1988)]. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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ANTIDIABETIC FORMULATION AND METHOD Inventor(s): PIPER, BETH ANNE; (HOPEWELL, NJ) Correspondence: Stephen B. Davis; Bristol-myers Squibb Company; Patent Department; P O Box 4000; Princeton; NJ; 08543-4000; US Patent Application Number: 20020177602 Date filed: November 3, 1999 Abstract: A low dose antidiabetic pharmaceutical formulation is provided, especially adapted for treating Type II diabetes in drug naive patients, which includes a combination of metformin (employed in a reduced amount (less than 800 mg metformin per day) compared to that employed in generally accepted medical practice) and at least one other antidiabetic agent such as a sulfonyl urea, for example, glyburide, which combination provides at least about substantially equivalent efficacy in treating diabetes in drug naive patients, as do antidiabetic formulations containing metformin employed in dosages prescribed in generally accepted medical practice for first line therapy in treating diabetes, but with substantially reduced side effects, such as hypoglycemia and/or gastrointestinal distress. A method for treating diabetes in drug naive human patients is also provided employing the above formulation to reduce insulin resistance and/or post-prandial glucose excursion and/or hemoglobin 1Ac, and/or increase postprandial insulin, thereby treating the diabetes. Excerpt(s): The present invention relates to a low dose pharmaceutical formulation for treating type 2 diabetes in drug naive patients, which includes metformin (preferably employed in reduced amounts compared to that employed in generally accepted medical practice) and another antidiabetic agent such as a sulfonyl urea, for example, glyburide, which formulation has at least substantially equivalent efficacy in treating type 2 diabetes as compared to prior art antidiabetic formulations containing metformin, but with substantially reduced side effects, and to a method for treating diabetes employing such formulations. The biguanide antihyperglycemic agent metformin disclosed in U.S. Pat. No. 3,174,901 is currently marketed in the U.S. in the form of its hydrochloride salt (Glucophage.RTM.), Bristol-Myers Squibb Company). The diagnosis and management of type 2 diabetes mellitus is rapidly undergoing progressive changes. It is now widely accepted that glycemic control makes a difference. The goal of diabetes therapy today is to achieve and maintain as near normal glycemia as possible to prevent the long-term microvascular and macrovascular complications of an elevated blood glucose. The diagnosis of diabetes has undergone significant changes as evidenced by the new ADA diagnostic and classification guidelines. Oral therapeutic options for the treatment of type 2 diabetes mellitus, until recently, have been severely limited. Prior to 1995, sulfonyl ureas had been the mainstay of oral diabetes agents in the United States. Sulfonyl ureas target one mechanism of hyperglycemia by augmenting insulin secretion from the beta cell. Since 1995, three new classes of agents have been added to the antidiabetes armamentarium for the management of hyperglycemia. Metformin, a biguanide, targets additional mechanisms of hyperglycemia by inhibiting hepatic glucose production and enhancing peripheral glucose uptake and thereby reduce insulin resistance; thiazolidinediones such as troglitazone, rosiglitazone and pioglitazone decrease peripheral insulin resistance; and alpha-glucosidase inhibitors such as acarbose and miglitol help control postprandial glucose excursion by delaying absorption of dietary carbohydrate. These agents are all indicated as monotherapy and some are indicated for use in combination therapy, generally, after monotherapy has been found to be inadequate.
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Blood glucose meter that reminds the user to test after a hypoglycemic event Inventor(s): Jones, Steven Paul; (Rochester, MN) Correspondence: Robert R. Williams, Patent Agent; Ibm Corporation, DEPT. 917; 3605 Highway 52 North; Rochester; MN; 55901-7829; US Patent Application Number: 20030211617 Date filed: May 7, 2002 Abstract: Methods, program product, and apparatus are provided for implementing a blood glucose meter that will remind the user to test his or her blood glucose after a programmable wait when a hypoglycemic event is detected. Diabetics frequently have a "rebound" hyperglycemic event (high blood glucose) occur as a result of a hypoglycemic event (low blood glucose). The disclosed invention allows the user to program the meter with a waiting period which he or she determines is appropriate to wait following a low blood glucose reading. At the end of this period, the meter will alert the user by way of an audible or tactile warning. Excerpt(s): The present invention relates to blood glucose meters, and in particular, to an inexpensive blood glucose meter that reminds the user to recheck his or her blood glucose after a programmable interval when the meter detects a hypoglycemic event. Insulin dependent diabetes mellitus (IDDM) is caused by the autoimmune destruction of the insulin producing islets of Langerhans in the pancreas. Insulin replacement therapy is the interim treatment for IDDM until such time as islet transplants, stem cell treatments, or other improved treatments become feasible. Insulin lowers the concentration of glucose in the blood, while food--in particular, carbohydrates--raises the concentration of glucose in the blood. The challenge of insulin therapy is to administer food and insulin in a manner that maintains blood glucose concentrations in an acceptable range, thereby avoiding hypoglycemia and hyperglycemia. Hyperglycemia (high blood glucose concentration) has adverse long-term consequences for the body. These consequences include kidney damage leading to kidney failure, microaneurisms in the retina causing blindness, and the blocking of capillaries in the extremities causing an inability to heal wounds and subsequent gangrene. Hypoglycemia (low blood glucose concentration) has an immediate adverse consequence of reduced brain function that leads to confusion and an inability to reason, remember, or react. In the extreme, hypoglycemia causes seizure, coma, and death. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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C-glycosides and preparation of thereof as antidiabetic agents Inventor(s): Kobayashi, Yoshinori; (Koushoku-shi, JP), Noda, Atsushi; (Nagano-shi, JP), Tomiyama, Akira; (Hanisina-gun, JP), Tomiyama, Hiroshi; (Hanishina-gun, JP), Tomiyama, Tsuyoshi; (Hanishina-gun, JP) Correspondence: Sherman & Shalloway; 413 North Washington Street; Alexandria; VA; 22314; US Patent Application Number: 20010041674 Date filed: January 23, 2001
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Abstract: C-glycoside derivatives are disclosed, which are represented by the following formula (I) and its pharmaceutical acceptable salt, and which are useful for the treatment and/or prevention of diabetes and hypoglycemia. 1wherein: with the provisos thatR.sub.1 is H, OH, lower alkyl, O-lower alkyl or 2;R.sub.2 is H, --COO-lower alkyl, 3;R.sub.5 is --CH.sub.2OH, --CH.sub.2OCO.sub.2-lower alkyl, 4 5-CH.sub.2OSO.sub.3H, --COOH or --COONa;wherein: A is 6(with the provisos that X is oxygen atom, nitrogen atom or sulfur atom R.sub.3 is lower alkyl when is 1, R.sub.3 is including --OH, --O-lower alkyl,. means saturated or unsaturated carbon bond;m is O or 1;n is 0, 1 or 2;above mentioned-lower alkyl means C.sub.1-C.sub.5.)or a pharmaceutical acceptable salt. Excerpt(s): This invention regarding to new C-glycosides which are useful for the treatment and/or prevention of diabetes and a pharmaceutical composition containing these compounds as active ingredients. And this invention is also including the method of preparation of C-glycosides. The anti-diabetic compounds which modulates energy valance and glucose levels in the body are required recently. The Na.sup.+-glucose cotransporter (SGLT) located on the chorionic membrane of the intestine and the kidney. Glucose is absorbed in the investive and the kidney mediated by SGLT. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Composition and method for maintaining blood glucose level by employing the hydrophilic matrix based oral controlled release antidiabetic composition Inventor(s): Dhawan, Sanju; (Chandigarh, IN), Singla, Anil Kumar; (Chandigarh, IN) Correspondence: John P. O'banion; O'banion & Ritchey Llp; Suite 1550; 400 Capitol Mall; Sacramento; CA; 95814; US Patent Application Number: 20030113371 Date filed: August 21, 2001 Abstract: A composition useful for reducing serum glucose levels by an oral controlled release system and a method for treating diabetes in a human being by controlling the blood glucose level (BGL) and reducing the complications associated with diabetic hyperglycemia and also the long term management of Non-Insulin Dependent Diabetes Mellitus (NIDDM) by avoiding the problems associated with the tight control of BGL, i.e., hypoglycemia tolerance and seizures. The composition is directed to a solid, hydrophilic matrix controlled release oral dosage form where the dosage form contains a therapeutically effective amount of antidiabetic drug in the matrix ensuring complete bioavailability of the drug from the matrix of the tablet. The formulation undergoes substantially or approaches zero order release of active drug and the concentration of the excepients and the water swellable polymers is chosen in such a way that the erosion or dissolution rate of the polymer is equal to the swelling rate of the polymer to get a constant release. Also, the concentration is chosen in such a way that the tablet will be fully dissolved at the same time the last of the drug is released and in addition a bioadhesive polymer may also be added to increase the residence time of the dosage form in the g.i.t. and at high concentration of the polymer, beta cyclodextrin may also be added to improve the release kinetics. Excerpt(s): (1) American Diabetes Association. Diabetes 1996 Vital Statistics. Rockville, Md.: American Diabetes Association, 1996. (2) Harris, M. I., Cowie, C. C., Stern, M. P. eds. Diabetes in America, 2nd. ed. National Institutes of Health. National Institute of Diabetes and Digestive and Kidney Diseases. NIH Publication No.95-1468, 1995. (3)
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Clark, C. M., Vinicor, F. Introduction: Risks and benefits of intensive management in non-insulin-dependent diabetes mellitus. The Fifth Regensrief Conference. Ann Intern Med, 124(1, pt 2), 81-85, 1996. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Hypoglycemic agent Inventor(s): Ikawa, Hiroshi; (Tokyo, JP), Inaba, Niro; (Tama-Shi, JP), Kojima, Kazuhiro; (Tokyo, JP), Kosono, Hideki; (Kamakura-Shi, JP), Nakamura, Takashi; (Tokyo, JP), Nishimura, Masato; (Tokyo, JP), Okada, Keiji; (Tokyo, JP) Correspondence: Oblon, Spivak, Mcclelland, Maier & Neustadt, P.C.; 1940 Duke Street; Alexandria; VA; 22314; US Patent Application Number: 20030191323 Date filed: January 2, 2003 Abstract: The present invention provides a hypoglycemic agent containing an acylsulfonamide derivative such as a compound of the following formula or an analog thereof, which agent is usable for preventing and curing diabetes: 1 Excerpt(s): The present invention relates a hypoglycemic agent having a hypoglycemic effect and also an activity of inhibiting acetyl CoA carboxylase (hereinafter referred to ACC). Diabetes is a diseases caused by various factors such as overeating, lack of exercise, stress and hereditary factors. The number of the patients suffering from diabetes is increasing as the life of the people is improved. At present, the number of diabetes cases is so large that this disease is called "a national disease" in Japan. Diabetes is classified into two types, i.e. insulin dependent diabetes mellitus (IDDM) and noninsulin dependent diabetes mellitus (NIDDM). In Japan, at least 90% of diabetes cases is NIDDM. Patients suffering from NIDDM scarcely have the subjective symptoms and when the patients are found to suffer from this disease, the disease has already progressed in many cases. In such a case, a suitable therapy is required for avoiding complications. For the treatment of NIDDM, dietetic therapy or kinetotherapy is employed at first. By such a therapy, the effects such as reduction in obesity, increase in the insulin sensitivity and reduction of insulin requirement in peripheries and reduction of endogenous insulin requirement can be expected. As a result, the blood glucose level can be controlled. However, in many cases, a sufficient effect in reducing the blood glucose level cannot be obtained by the dietetic therapy or kinetotherapy. In such cases, the patients are treated with medicines. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Method of screening hypoglycemic substance by using stat inhibitory factor-1 Inventor(s): Kishimoto, Tadamitsu; (Osaka, JP), Naka, Tetsuji; (Osaka, JP) Correspondence: Sughrue Mion, Pllc; 2100 Pennsylvania Avenue, N.W.; Washington; DC; 20037; US Patent Application Number: 20030186215 Date filed: March 10, 2003 Abstract: The present invention discloses a screening method for a substance, which could be a therapeutic agent for diabetes with insulin resistance through regulating a
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function of a molecule involved in insulin signaling pathway. More specifically, the present invention discloses a screening method for a substance having hypoglycemic activity, which is characterized by contacting a sample to STAT-induced inhibitor of STAT function-1 in the presence of insulin, and by detecting inhibitory activity of STATinduced inhibitor of STAT function-1 by a substance in the sample, as an index. Excerpt(s): The present invention relates to a screening method for a substance having hypoglycemic activity which is characterized by contacting a sample to STAT-induced inhibitor of STAT function-1 in the presence of insulin, and by detecting inhibitory activity of STAT-induced inhibitor of STAT function-l by a substance in the sample, as an index. STAT (Signal Transducer and Activator of Transcription) is a molecule that is activated by stimulation with cytokine(s). STAT-induced inhibitor of STAT function-1 is a protein that is induced by STAT and inhibits cytokine signaling through suppressing activation of Janus Kinase (JAK). STAT-induced inhibitor of STAT function-1 (hereinafter, simply referred to as "SSI-1", though the abbreviation "SSI-1", "SOCS-1" or "SIIS-1" have been used) was first isolated from mouse by the inventors of the present invention (PCT Publication No. WO98/30688 and Naka, T. et al, Nature, 387, 924-929 (1997)). So far, eight members of the SSI family molecule, including SSI-2 and SSI-3 (Minamoto, S. et al., Biochem. Biophys. Res. Commun., 237, 79-83 (1997)),have been identified as an inhibitor. The inventors of the present invention have also already isolated human SSI-1 (Minamoto, S. et al., Biochem. Biophys. Res. Commun., 237, 79-83 (1997)). The functional domain of SSI-1 was determined by an experiment using mutant genes of SSI-1 (Narazaki, M. et al., Proc. Natl. Acad. Sci. U.S.A., 95, 13130-13134 (1998)). More specifically, it is known that 24 amino acid residues existing in N-terminus of SH2 domain (pre-SH2) as well as SH2 domain are essential for the suppression of phosphorylation of JAK, and that SSI-1 associates to JAK through its SH2 and pre-SH2 domains. Moreover, part of the biological function of SSI-1 in vivo has been identified by the inventors of the present invention using SSI-1-deficient mice. In SSI-1-deficient mice, apoptosis was detected in several organs such as lymphocytes, heart and liver, in which SSI-1 was expressed as the ages passed, indicating that SSI-1 closely relates to survival of a cell, especially to an inflammation (Naka, T. et al., Proc. Natl. Acad. Sci. U.S.A., 95, 15575-15582 (1998)). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Method, system, and computer program product for the evaluation of glycemic control in diabetes from self-monitoring data Inventor(s): Cox, Daniel J.; (Charlottesville, VA), Kovatchev, Boris P.; (Amherst, VA) Correspondence: Robert J Decker; University OF Virginia Patent Foundation; 1224 West Main Street Suite 1 110; Charlottesville; VA; 22903; US Patent Application Number: 20030212317 Date filed: September 26, 2002 Abstract: A method, system, and computer program product related to the diagnosis of diabetes, and is directed to predicting the long term risk of hyperglycemia, and the longterm and short-term risks of severe hypoglycemia in diabetics, based on blood glucose readings collected by a self-monitoring blood glucose device. The method, system, and computer program product pertain directly to the enhancement of existing home blood glucose monitoring devices, by introducing an intelligent data interpretation component capable of predicting both HbA.sub.1c and periods of increased risk of hypoglycemia, and to the enhancement of emerging continuous monitoring devices by the same
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features. With these predictions the diabetic can take steps to prevent the adverse consequences associated with hyperglycemia and hypoglycemia. Excerpt(s): The present invention claims priority from U.S. Provisional Patent Application Serial No. 60/193,037 filed Mar. 29, 2000, entitled "Algorithm for the Evaluation of Glycemic Control in Diabetes From Self-Monitoring Data" the entire disclosure of which is hereby incorporated by reference herein. The present system relates generally to Glycemic Control of individuals with diabetes, and more particularly to a computer-based system and method for evaluation of predicting glycosylated hemoglobin (HbA.sub.1c and HbA.sub.1) and risk of incurring hypoglycemia. Extensive studies, including the Diabetes Control and Complications Trial (DCCT) (See DCCT Research Group: The Effect Of Intensive Treatment Of Diabetes On The Development And Progression Of Long-Term Complications Of Insulin-Dependent Diabetes Mellitus. New England Journal of Medicine, 329: 978-986, 1993), the Stockholm Diabetes Intervention Study (See Reichard P, Phil M: Mortality and Treatment Side Effects During Long-term Intensified Conventional Insulin Treatment in the Stockholm Diabetes Intervention Study. Diabetes, 43: 313-317, 1994), and the United Kingdom Prospective Diabetes Study (See UK Prospective Diabetes Study Group: Effect of Intensive Blood Glucose Control With Metformin On Complications In Patients With Type 2 Diabetes (UKPDS 34). Lancet, 352: 837-853, 1998), have repeatedly demonstrated that the most effective way to prevent the long term complications of diabetes is by strictly maintaining blood glucose (BG) levels within a normal range using intensive insulin therapy. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Methods and devices for prediction of hypoglycemic events Inventor(s): Potts, Russell O.; (San Francisco, CA), Tierney, Michael J.; (San Jose, CA) Correspondence: Cygnus, INC.; Intellectual Property DEPT.; 400 Penobscot Drive; Redwood City; CA; 94063; US Patent Application Number: 20020106709 Date filed: August 10, 2001 Abstract: Described herein are methods, devices, and microprocessors useful for predicting a hypoglycemic event in a subject. The hypoglycemic predictive approach described herein utilizes information obtained from a data stream, e.g., frequently obtained glucose values (current and/or predicted), body temperature, and/or skin conductance, to predict incipient hypoglycemic events and to alert the user. Excerpt(s): This application is related to U.S. Provisional Patent Application Serial No. 60/226,431, filed Aug. 18, 2000, from which priority is claimed under 35 USC.sctn. 119(e)(1), and which application is incorporated herein by reference in its entirety. Described herein are methods, devices, and microprocessors useful for predicting a hypoglycemic event in a subject. The present invention for prediction of hypoglycemic events typically employs multiple parameters in the prediction. Such parameters include, but are not limited to, glucose readings (current and/or predicted), body temperature, and/or skin conductance. Hypoglycemia is the most critical acute complication of diabetes. Typically used present methods of self-monitoring of blood glucose (SMBG) provide periodic measurements of blood glucose obtained from a finger stick. This method produces measurements that, while very accurate, are too infrequent to detect hypoglycemic episodes. Frequently, in order to avoid hypoglycemia, diabetics
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maintain abnormally high blood glucose levels to provide a "buffer" against low blood glucose levels. This constant high blood glucose level is the root cause of most long-term complications of diabetes, namely, retinopathy, neuropathy, nephropathy, and cardiovascular disease. In effect, the present SMBG methods are forcing many diabetics to pay for a lower rate of acute complications with a higher rate of chronic complications in later life. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Methods and systems for assessing glycemic control using predetermined pattern label analysis of blood glucose readings Inventor(s): Armbrecht, Eric Stephen; (St. Louis, MO), Bortz, Jonathan David; (St. Louis, MO) Correspondence: Michael T. Marrah; Sonnenschein Nath & Rosenthal; Wacker Drive Station, Sears Tower; P.O. Box #061080; Chicago; IL; 60606-1080; US Patent Application Number: 20030216628 Date filed: January 28, 2002 Abstract: Methods and systems for analyzing blood glucose readings comprising the steps of obtaining a plurality of blood glucose readings taken within a predetermined time category and time period, performing first calculations on said readings based on a predetermined normal range of glycemia in a first analysis and selecting and applying a pattern label having predetermined criteria to the plurality of blood glucose readings by comparing the results of the first calculations to the pattern label criteria. The invention may also include the steps of performing second calculations on said readings based on predetermined thresholds for severe hyperglycemia and severe hypoglycemia and selecting and appending a severity suffix having predetermined severity criteria to said pattern label by comparing the results of the second calculations to the severity criteria as well as performing third calculations on said readings based on a predetermined normal range of glycemia and selecting and appending a minor comment having minor comment criteria to said pattern label by comparing the results of the third calculations to the comment criteria. Excerpt(s): The present invention is in the field of chemical arts, specifically, the field of blood glucose level analysis. Proper analysis of blood glucose levels is crucial to providing optimal care to diabetic patients. However, proper analysis of blood glucose levels for even a single patient requires the analysis of mountains of individual readings from various time categories taken over various spans to determine the clinical significance of the individual readings and any information shown by groups of readings. Such analysis is time-consuming and tedious for medical professionals to perform on any significant scale. Moreover, the lack of generally accepted analytical terms for analyzing the raw blood glucose reading data increases the complexity of the analysis and burdens the exchange of analysis data between medical professionals. This makes it more difficult for medical professionals to correlate a given series of readings with the proper course of medical intervention. Of course, it also makes educating patients about their own condition and treatment options difficult. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Methods for the treatment and prevention of metabolic diseases including diabetes Inventor(s): Belna, David; (Costa Mesa, CA) Correspondence: Ray K. Shahani, ESQ.; Twin Oaks Office Plaza; Suite 112; 477 Ninth Avenue; San Mateo; CA; 94402-1854; US Patent Application Number: 20020168431 Date filed: March 7, 2002 Abstract: A method of treating metabolic diseases such as diabetes, hypoglycemia, or hypoglycemia in a patient includes providing Chia seeds, having a seed body, adding water to the Chia seeds to form a gel, separating the seed body from the gel, extracting a water soluble fiber including a polysaccharide from the gel, and delivering a therapeutic amount of the fiber to the digestive tract of the patient. The step of delivering a therapeutic amount can include combining the fiber and polysaccharide with a carbohydrate-based food. The method can further include adding a bio-adhesive, and/or an amylase inhibitor to the gel, or the polysaccharide. Excerpt(s): This Application is related to and incorporates herein by reference, in its entirety, U.S. Provisional Application Serial No. 60/274,485 filed Mar. 7, 2001 entitled METHODS FOR THE TREATMENT AND PREVENTION OF METABOLIC DISEASES INCLUDING DIABETES, and claims any and all benefits to which it is entitled therefrom. The present invention relates to the treatment of metabolic diseases including diabetes mellitus (diabetes), and particularly to methods of optimizing the digestion of carbohydrates in humans. Research reveals that over half of all deaths in U.S. are dietrelated, that is, the cause of death has been identified as having statistical correlation to a particular dietary scheme. Metabolic diseases including cardiovascular disease and diabetes mellitus had been statistically linked to dietary habits. Cardiovascular disease is the top killer. Cancer is second. Diabetes and its complications are the third leading cause of death and Canada and U.S. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Methods for treating insulin resistance and identifying patients at risk for the disease Inventor(s): Chasalow, Fred I.; (San Carlos, CA) Correspondence: Darby & Darby P.C.; 805 Third Avenue; New York; NY; 10022; US Patent Application Number: 20020165127 Date filed: February 19, 2002 Abstract: The present invention is directed to compositions and methods for treating insulin resistance and for ameliorating pathological conditions associated with insulin resistance. Also disclosed are methods for identifying patients at risk for developing non-insulin dependent diabetes melitis or insulin resistance. Also disclosed are methods for identifying patients at risk for developing or suffering from reactive hypoglycemia and methods of treatment thereof. Excerpt(s): This application claims priority under 35 U.S.C.sctn.119 from Provisional U.S. patent application No. 60/034,504 filed Dec. 24, 1996, and Provisional U.S. patent applicaton No. 60/037,417 filed Feb. 21, 1997, the entire disclosures of which are hereby incorporated by reference. This invention pertains to methods and compositions for treating insulin resistance and for ameliorating pathological conditions associated with insulin resistance. Also disclosed herein are methods for identifying patients at risk for
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developing non-insulin dependent diabetes melitis or insulin resistance. The invention also pertains to methods for identifying patients at risk for developing or suffering from reactive hypoglycemia and methods of treatment thereof. Insulin resistance is an extremely common pathophysiological phenomenon that is implicated in non-insulindependent diabetes (NIDDM), atherosclerotic cardiovascular disease, syndrome x, obesity, hypertension, dyslipidemias, and polycystic ovarian syndrome, among other pathological conditions (Moller et al., Diabetes Care 19:396, 1996). At least in some instances, insulin resistance is likely to be caused by competition between insulin and IGF-2 for binding to the insulin receptor, which is present on a large number of different cell types and which mediates the body's response to insulin. This is based in part on the correlation between IGF-2 concentrations and insulin requirements in children with diabetes (Chasalow et al., Amer.Ped.Soc. 1995 meeting). Without wishing to be bound by theory, it is believed that the presence of an increased level of circulating IGF-2 can affect the occupancy of the insulin receptor so as to contribute to insulin resistance; and that, conversely, lowering the circulating levels of IGF-2 in a patient will decrease the magnitude of insulin resistance. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Methods of monitoring glucose levels in a subject and uses thereof Inventor(s): Ackerman, Neil; (San Carlos, CA) Correspondence: Cygnus, INC.; Intellectual Property DEPT.; 400 Penobscot Drive; Redwood City; CA; 94063; US Patent Application Number: 20020026111 Date filed: August 10, 2001 Abstract: Methods of frequently monitoring glucose amounts and/or concentrations in a subject who is at risk for hypoglycemia, hyperglycemia, and/or glucose level fluctuations that put the subject at risk are provided. Also provided are methods of monitoring the effects of one or more pharmaceutical compositions on the levels of glucose in a subject. Excerpt(s): This application is related to U.S. Provisional Patent Application Serial No. 60/228,617, filed Aug. 28, 2000, from which priority is claimed under 35 USC.sctn.119(e)(1), and which application is incorporated herein by reference in its entirety. The present invention is in the field of medical devices and methods of use thereof. More particularly it relates to methods of using glucose monitoring devices to monitoring glucose amounts and/or concentrations in a subject who is at risk for hypoglycemia, hyperglycemia, or fluctuations toward hypoglycemia and/or hyperglycemia. The methods also include methods of monitoring the effects of one or more pharmaceutical compositions on the levels of glucose in a subject. The level, presence, and/or absence of glucose in a subject can have a number of consequences. For example, fluctuations of blood glucose levels can result in one of two physiological states, hypoglycemia and hyperglycemia. Hypoglycemia is defined as plasma glucose levels below normal. Hypoglycemia can be symptomatic or asymptomatic. For example, subjects suffering from postprandial hypoglycemia generally have symptoms of adrenergic stimulation including diaphoresis, anxiety, irritability, palpitations, tremor, and hunger. Such symptoms typically occur from about 2 to 4 hours postprandially and tend to occur suddenly with symptoms generally subsiding in about 15 to 20 minutes. Hypoglycemia can be caused by release of adrenergic and cholinergic hormones. Postprandial hypoglycemia is often idiopathic, however, it can be caused by early
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diabetes, alcohol intake, renal failure, and drug treatments. In addition, a category of hypoglycemia exists which is designated as fasting hypoglycemia. Clinically, this form of hypoglycemia may have symptoms of neuroglycopenia including headache, fatigue, and mental dullness. In more severe cases, hypoglycemia can progress to confusion, blurring of vision, seizure, and ultimately loss of consciousness or seizure. Fasting hypoglycemia can occur with a fast of greater than 4 hours, and further can be caused by insulinoma (resulting from self-administered insulin or intake of other hypoglycemic agents, alcohol abuse, liver disease (e.g., decreased gluconeogenesis), pituitary insufficiency, or adrenal insufficiency). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Naturally extracted and synthetic hypoglycemic or hypolipidemic compositions Inventor(s): Aharoni, Anat; (Haifa, IL), Margalit, Alon; (Tivon, IL), Mirsky, Nitsa; (Nofit, IL), Sussan, Sherbel; (Tarshicha, IL) Correspondence: Stroock & Stroock & Lavan Llp; 180 Maiden Lane; New York; NY; 10038; US Patent Application Number: 20010021397 Date filed: April 26, 2001 Abstract: Compositions having hypoglycemic and/or hypolipidemic activity are isolated from natural sources including yeast and Saltbush (Atriplex halimus). In addition, synthetic chromium complexes were prepared. Compositions possessing hypoglycemic and/or hypolipidemic activity with or without chromium containing natural and synthetic compounds are formulated for use in animals and humans. Methods for use of the compositions alone, or in combination with antioxidant agents, for regulating glucose and lipid levels in diabetes, cardiovascular diseases, inflammatory and cell proliferative diseases and in skin conditions, are presented. Excerpt(s): The present invention is directed to processes of isolating purified compositions with or without chromium containing compounds, from a variety of natural sources including, but not limited to, a yeast strain S. carlsbergensis, or S. cerevisiae, or any commercial source of yeast extract; or from the Saltbush, Atriplex halimus, growing in the Negev Desert near the Dead Sea and other and areas in the middle east. The invention also comprises production of synthetic sources of chromium, including, but not limited to chromium gluconate, chromium sulfate, chromiumcysteine, chromium-N-acetyl cysteine, chromium-glutathione, chromium acetate, chromium citrate, chromium ascorbate or chromium tartarate. The invention is also directed to formulations with or without chromium containing natural compounds or the synthetic chromium complexes, which specifically regulate glucose tolerance, glucose and lipid metabolism, insulin action, and metabolic activities in mammals who may be at an enhanced risk for or having a diabetic condition or cardiovascular diseases. In the practice of the method of treating diabetes, compositions containing the chromium complexes or the natural compositions with or without chromium containing compounds are used to regulate the diabetes related metabolic disregulation without general cytotoxic effects. Chromium (Cr) has been known as an essential trace element in animal and human nutrition. Cr deficiency may result in various symptoms including increased concentrations of circulating insulin, elevated blood glucose and cholesterol, decreased insulin receptor number, elevated triglyceride and free fatty acid levels and reduced high-density lipoprotein (HDL) cholesterol levels. These metabolic abnormalities, in general, are associated with risk for and/or incidence of diabetes.
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Moreover, chromium levels in most organs decline with age and in diabetics the chromium levels are even lower-than in other healthy adults. Anderson, R. A., Clin. Physiol. Biochem. 4: 31-41 (1986). Malnutrition associated with Cr deficiency brings an impaired glucose tolerance. However, inorganic Cr compounds are poorly absorbed by the gut, whereas organic Cr components are well absorbed in the body. Glucose Tolerance Factor (GTF) is an organic complex of chromium present in several natural sources, the richest among them is Brewer's yeast. GTF was found to improve glucose tolerance in 50% of elderly patients with impaired glucose tolerance after two months of treatment. Despite these effects, the structure of GTF has not been identified as of yet. Several naturally occurring organic Cr compounds have been proposed to serve as GTF, for example, a partially purified cationic Cr compound extracted from yeast, soluble in water and has an absorption spectrum at 260 nm, or the low-molecular-weight Crbinding substance isolated from mouse or rabbit liver or bovine colostrum which has anionic properties. These organic Cr compounds have heretofore been used as crude extracts and the properties of their individual components remain uncharacterized. Evans, G. W. et al., Biochem. Biophys. Res. Commun, 50:718-722 (1973). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
NMDA receptor agonist pharmaceutical compositions Inventor(s): Hong, Jinyang; (Stonington, CT), Kim, Yesook; (Branford, CT) Correspondence: Gregg C. Benson; Pfizer INC.; Patent Department, MS 4159; Eastern Point Road; Groton; CT; 06340; US Patent Application Number: 20020111366 Date filed: December 5, 2001 Abstract: This invention relates to stable pharmaceutical compositions of the NMDA receptor agonist, (1S,2S)-1-(4-hydroxyphenyl)-2-(4-hydroxy-4-phenylpiperi- din-1-yl)-1propanol], methods of preparing such pharmaceutical compositions and methods of treating stroke, spinal cord trauma, traumatic brain injury, multiinfarct dementia, CNS degenerative diseases such as Alzheimer's disease, senile dementia of the Alzheimer's type, Huntington's disease, Parkinson's disease, epilepsy, amyotrophic lateral sclerosis, pain, AIDS dementia, psychotic conditions, drug addictions, migraine, hypoglycemia, anxiolytic conditions, urinary incontinence and an ischemic event arising from CNS surgery, open heart surgery or any procedure during which the function of the cardiovascular system is compromised using the pharmaceutical compositions. Excerpt(s): This invention provides stable pharmaceutical compositions of the Nmethyl-D-aspartic acid (NMDA) receptor antagonist, (1S,2S)-1-(4-hydroxyphenyl)-2-(4hydroxy-4-phenylpiperidin-1-yl)-1-propanol, methods of preparing such pharmaceutical compositions and methods of treating stroke, spinal cord trauma, traumatic brain injury, multiinfarct dementia, CNS degenerative diseases such as Alzheimer's disease, senile dementia of the Alzheimer's type, Huntington's disease, Parkinson's disease, epilepsy, amyotrophic lateral sclerosis, pain, AIDS dementia, psychotic conditions, drug addictions, migraine, hypoglycemia, anxiolytic conditions, urinary incontinence and an ischemic event arising from CNS surgery, open heart surgery or any procedure during which the function of the cardiovascular system is compromised, using the pharmaceutical compositions of this invention. (1S,2S)-1-(4Hydroxyphenyl)-2-(4-hydroxy-- 4-phenylpiperidin-1-yl)-1-propanol (hereafter referred to as the "Compound") is a neuroprotecting agent that is useful for the treatment of stroke, spinal cord trauma, traumatic brain injury, multiinfarct dementia, CNS
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degenerative diseases such as Alzheimer's disease, senile dementia of the Alzheimer's type, Huntington's disease, Parkinson's disease, epilepsy, amyotrophic lateral sclerosis, pain, AIDS dementia, psychotic conditions, drug addictions, migraine, hypoglycemia, anxiolytic conditions, urinary incontinence and an ischemic event arising from CNS surgery, open heart surgery or any procedure during which the function of the cardiovascular system is compromised. The Compound exhibits activity as an NMDA receptor antagonist. NMDA is an excitatory amino acid involved in excitatory neurotransmission in the central nervous system. NMDA antagonists are compounds that block the NMDA receptor by interacting with the receptor's binding site. Antagonists of neurotransmission at NMDA receptors are useful therapeutic agents for the treatment of neurological disorders. U.S. Pat. No. 4,902,695 is directed to series of competitive NMDA antagonists useful for the treatment of neurological disorders, including epilepsy, stroke, anxiety, cerebral ischemia, muscular spasms, and neurodegenerative disorders such as Alzheimer's disease and Huntington's disease. U.S. Pat. No. 4,968,878 is directed to a second series of competitive NMDA receptor antagonists useful for the treatment of similar neurological disorders and neurodegenerative disorders. U.S. Pat. No. 5,192,751 discloses a method of treating urinary incontinence in a mammal, which comprises administering an effective amount of a competitive NMDA antagonist. Commonly assigned U.S. Pat. No. 5,272,160 and commonly assigned U.S. Pat. No. 5,710,168 (the disclosures of which are hereby incorporated by reference) disclose the Compound and methods of using the Compound for treatment of diseases or conditions that are susceptible to treatment by blocking NMDA receptor sites, including stroke, spinal cord trauma, traumatic brain injury, multiinfarct dementia, CNS degenerative diseases, epilepsy, amyotrophic lateral sclerosis, pain, AIDS dementia, psychotic conditions, drug addictions, migraine, hypoglycemia, anxiolytic conditions, urinary incontinence and ischemic events. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
NOVEL AMYLIN AGONIST PEPTIDES AND USES THEREFOR Inventor(s): ALBRECHT, ELISABETH; (SAN DIEGO, CA), GAETA, LAURA S. L.; (LA JOLLA, CA), JONES, HOWARD; (POWAY, CA) Correspondence: Bradford J. Duft, ESQ.; Brobeck, Phleger & Harrison Llp; 12390 EL Camino Real; San Diego; CA; 92130; US Patent Application Number: 20020187923 Date filed: December 6, 1999 Abstract: Agonist analogs of amylin and related pharmaceutical compositions, and methods of treatment of diabetes and other insulin-requiring states, as well as methods of treatment of hypoglycemia, are provided. Excerpt(s): This is a division of application Ser. No. 08/447,849 filed May 23, 1995, which is a continuation of application Ser. No. 07/794,266 filed Nov. 19, 1991, which is a continuation-in-part of application Ser. No. 07/667,040 filed Mar. 8, 1991, which prior applications are hereby incorporated by reference in their totalities (including drawings). The field of the invention is medicine, particularly the treatment and prevention of hypoglycemic conditions and other conditions in which enhanced amylin action is of benefit, including insulin-requiring states such as diabetes mellitus. More specifically, the invention relates to the preparation and use of agonist analogues of the peptide hormone amylin. Diabetes mellitus is a serious metabolic disease that is defined by the presence of chronically elevated levels of blood glucose (hyperglycemia). This
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state of hyperglycemia is the result of a relative or absolute lack of activity of the peptide hormone, insulin. Insulin is produced and secreted by the.beta. cells of the pancreas. Insulin is reported to promote glucose utilization, protein synthesis, and the formation and storage of neutral lipids. Glucose, the principal source of carbohydrate energy, is stored in the body as glycogen, a form of polymerized glucose, which may be converted back into glucose to meet metabolism requirements. Under normal conditions, insulin is secreted at both a basal rate and at enhanced rates following glucose stimulation, all to maintain metabolic homeostasis by the conversion of glucose into glycogen. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Novel glutamine: fructose-6-phosphate amidotransferase, its production and use Inventor(s): Hikichi, Yukiko; (Tsukuba, JP), Nishi, Kazunori; (Tsukuba, JP), Shintani, Yasushi; (Tsukuba, JP) Correspondence: Dike, Bronstein, Roberts And Cushman,; Intellectual Property Practice Group; Edwards & Angell, LLP.; P.O. Box 9169; Boston; MA; 02209; US Patent Application Number: 20020028198 Date filed: January 29, 2001 Abstract: This invention relates to glutamine:fructose-6-phosphate amidotransferase, or its partial peptide or a salt thereof; a DNA coding for the protein; a recombinant vector; a transformant; a method for producing the protein; a pharmaceutical composition comprising the protein, its partial peptide or a salt thereof; and an antibody against the protein or its partial peptide. The protein, its partial peptide or a salt thereof, and the DNA are useful for a prophylactic or therapeutic agent for hypoglycemia. The antibody can be used in the assay of the protein, its partial peptide or a salt thereof. The protein, its partial peptide or a salt thereof is useful as a reagent for the screening for candidate medical compounds. Excerpt(s): The present invention relates to a novel protein showing an activity of glutamine:fructose-6-phosphate amidotransferase (hereinafter briefly referred to as GFAT), etc. and to a DNA coding for the protein. In recent years, the diabetic population has increased steadily and diabetes is attracting attention as one of adult diseases. Noninsulin-dependent diabetes mellitus (NIDDM) is a type of diabetes frequently found in Japan and its early detection and timely treatment are necessary to prevent the disease. Although the factors causative of NIDDM have not been fully elucidated, recent advances have provided important new insights into this process. It is now well established that abnormalities in insulin sensitive mechanisms and reduced secretion of insulin are causes of insufficient insulin activity in NIDDM. In Europe and America, insulin resistance is predominant in patients with NIDDM while, in Japan, insulin hyposecretion is often the major cause. With recent advances in molecular biology, the cellular and molecular mechanisms underlying insulin resistance such as the insulin receptor structure and the mechanism of signal transduction downstream of the receptor, have been investigated in detail. During the last decade, glucose transporter genes has been cloned and the relationship between mutations in the genes and the process of diabetes has been studied. However, the insulin, glucokinase and mitochondrial gene abnormalities so far elucidated, taken together, account for not more than 1% of NIDDM cases. Other gene abnormalities are to be revealed in the future. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Novel polypeptide of protein p140 and DNAs encoding it Inventor(s): Kitagawa, Koichiro; (Osaka, JP), Ohno, Hiroyuki; (Osaka, JP), Tajima, Hisao; (Osaka, JP) Correspondence: Sughrue Mion, Pllc; 2100 Pennsylvania Avenue, NW; Washington; DC; 20037-3213; US Patent Application Number: 20030170865 Date filed: July 3, 2002 Abstract: The present invention is related to a novel protein p140 polypeptide which is a key protein involved in the signal transmission system of insulin; method for preparation of it; DNA encoding the said polypeptide; vector derived the said DNA; host cells transformed the said vector; antibody of the said polypeptide; pharmaceutical composition containing the said peptide or antibody; method for the prevention and/or treatment of diabetes, which is characterized by tyrosine phosphorylation of the said protein p140; agent for the prevention and/or treatment for the currently said the prevention and/or treatment method; agent for the prevention and/or treatment of diabetes, which is characterized by containing a compound which can tyrosine phosphorylation of protein p140, as active ingredient and the screening methods of the said prevention and/or treatment agent.Tyrosine phosphorylation of protein p140 is an essential step in the induction of hypoglycemia by glucose uptake. Method and agent of prevention and/or treatment based on tyrosine phosphorylation of protein p140 in the present invention is not only improve the diabetes-derived hyperglycemic conditions but are also useful for the treatment and/or prevention of diabetes, especially noninsulin dependent diabetes mellitus (NIDDM). Excerpt(s): Diabetes, an abnormal metabolic disease, is induced by a defect in the mechanism of glucose metabolism. Under normal conditions, glucose metabolism occurs as follows: Carbohydrates, consumed in the form of food, are digested to glucose in the intestines prior to absorption into the circulatory system. Pancreatic.beta. cells respond to an increase in the blood glucose level by secreting insulin, which in turn stimulates the target peripheral tissues (muscles and liver) to decrease the blood glucose level by enhancing tissue absorption of the blood glucose followed by conversion to glycogen for storage. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Piperidine derivatives as subtype selective N-methyl-D-aspartate antagonists Inventor(s): Kornberg, Brian Edward; (Ann Arbor, MI), Lewthwaite, Russell Andrew; (Cambridge, GB), Manning, David; (Duanesburg, NY), Nikam, Sham Shridhar; (Ann Arbor, MI), Scott, Ian Leslie; (Delanson, NY) Correspondence: David R. Kurlandsky; Warner-lambert Company; 2800 Plymouth Road; Ann Arbor; MI; 48105; US Patent Application Number: 20030018021 Date filed: November 30, 2001 Abstract: Described are piperidines of Formula I 1and pharmaceutically acceptable salts thereof. The compounds of Formula I are antagonists of NMDA receptor channel complexes useful for treating cerebral vascular disorders such as, for example, stroke, cerebral ischemia, central nervous system disorders, depression, trauma, hypoglycemia,
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neurodegenerative disorders, anxiety, migraine headache, convulsions, Parkinson's disease, aminoglycoside antibiotics-induced hearing loss, psychosis, glaucoma, CMV retinitis, opioid tolerance or withdrawal, pain, especially chronic pain, neuropathic pain, or surgical pain, or urinary incontinence. Excerpt(s): The invention relates to piperidine derivatives as N-Methyl-D-Aspartate (NMDA) antagonists useful in the treatment of diseases and disorders responsive to antagonism of NMDA receptors. Many of the physiological and pathophysiological effects of the endogenous excitatory neurotransmitter glutamate are mediated via actions at N-Methyl-D-Asparate (NMDA) receptors. Over-excitation of the NMDA receptors on postsynaptic cells-mediated by excessive release of glutamate from nerve endings or glial cells-results in a massive calcium ion influx through a calcium ion channel into neuronal cells, leading to neuronal cell death. These events occur under ischemic or hypoxic conditions such as, for example, stroke, hypoglycemia, cardiac arrest, or acute physical trauma. NMDA receptors in vivo form an NMDA receptor channel complex in cell walls comprising at least three binding domains, including a glutamic acid (or NMDA) recognition site, a channel blocking binding site, and a strychnine-insensitive glycine binding site. Physiologically, a blockade of at least one of these sites terminates the channel opening of the NMDA receptor, thereby preventing calcium ion influx into cells. Accordingly, an NMDA receptor antagonist is therapeutically useful because it minimizes damage to the central nervous system induced by calcium ion influx under ischemic or hypoxic conditions. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Substituted quinazolines and analogs and the use thereof Inventor(s): Cai, Sui X.; (San Diego, CA), Lan, Nancy C.; (Altadena, CA), Upasani, Ravi; (Sunnyvale, CA) Correspondence: Sterne, Kessler, Goldstein & Fox Pllc; 1100 New York Avenue, N.W., Suite 600; Washington; DC; 20005-3934; US Patent Application Number: 20030033089 Date filed: August 16, 2002 Abstract: The invention relates to novel quinazolines and heterocycles which are antagonists or positive modulators of AMPA receptors, and the use thereof for treating, preventing or ameliorating neuronal loss associated with stroke, global and focal ischemia, CNS trauma, hypoglycemia and surgery, as well as treating or ameliorating neurodegenerative diseases including Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's disease, Parkinson's disease and Down's syndrome, treating, preventing or ameliorating the adverse consequences of the overstimulation of the excitatory amino acids, treating, preventing or ameliorating anxiety, psychosis, convulsions, chronic pain, glaucoma, retinitis, urinary incontinence, muscular spasm and inducing anesthesia, as well as for treating or ameliorating the adverse consequences of excitatory amino acid deficiency such as schizophrenia, myoclonus, Alzheimer's disease and malnutrition and neural maldevelopment, and as cognition and learning enhancers. Excerpt(s): This invention is in the field of medicinal chemistry. In particular, the invention is related to novel substituted quinazolines and analogs thereof. These compounds are antagonists of x-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) ionotropic receptors. Certain of these compounds are positive modulators of AMPA receptors. The invention also is directed to the use of novel substituted
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quinazolines and analogs thereof for the treatment of neuronal damage following global and focal ischemia, and for the treatment or prevention of neurodegenerative conditions, as anticonvulsants, as cognitive enhancers, and for the treatment of schizophrenia, Parkinson's disease and myoclonus. The compounds of the invention are also useful for treatment or prevention of pain, including acute and chronic pain. The invention also is directed to a process for the preparation of the substituted quinazolines and analogs thereof. Excitatory amino acid receptors are classified into two general types. Receptors that are directly coupled to the opening of cation channels in the cell membrane of the neurons are termed "ionotropic." This type of receptor has been subdivided into at least three subtypes, which are defined by the depolarizing actions of the selective agonist N-methyl-D-aspartate (NMDA),.alpha.-amino-3-hydroxy-5methylisoxazole-4-- propionic acid (AMPA), and kainic acid (KA). The second general type is the G-protein or second messenger-linked "metabotropic" excitatory amino acid receptor. This second type, when activated by the agonists quisqualate, ibotenate, or trans-1-aminocyclopentane-1,3-dicarboxylic acid, leads to enhanced phosphoinositide hydrolysis in the postsynaptic cell. Both types of receptors appear not only to mediate normal synaptic connections during development, but also change in the efficiency of synaptic transmission throughout life. (Schoepp, Bockaert, and Sladeczek, Trends Pharm. Sci. 11:508 (1990); McDonald and Johnson, Brain Res. Rev. 15:41 (1990)). The excessive or inappropriate stimulation of excitatory amino acid receptors leads to neuronal cell damage or loss by a mechanism known as excitotoxicity. The medical consequences of such neuronal degeneration makes the abatement of these degenerative neurological processes an important therapeutic goal. (See U.S. Pat. No. 5,284,957). Antagonists of the AMPA receptor are considered useful in treating, preventing and ameliorating a number of neurologic disorders which are due to overstimulation by the excitatory amino acids. These include acute neurologic disorders such as domoic acid poisoning; cerebral ischemia, global ischemia associated with cardiac arrest; stroke; spinal cord trauma; hypoxia; anoxia; poisoning by carbon monoxide, manganese or cyanide; hypoglycemia; mechanical trauma to the nervous system; epileptic seizures; and chronic neurologic disorders such as Huntington's disease, neuronal injury associated with HIV and AIDS, AIDS dementia, neuropathic pain syndrome, olivopontocerebral atrophy, Parkinson's disease, amyotrophic lateral sclerosis, mitochondrial abnormalities, Alzheimer's disease, hepatic encephalopathy, Tourette's syndrome, drug addiction and urinary incontinence (see Lipton and Rosenberg, N. Engl. J. Med. 330: 613-622 (1994)) and treatment or amelioration of a number of chronic neurologic disorders such as schizophrenia. AMPA receptor antagonists are also useful in treating, preventing and ameliorating acute and chronic pain, pain associated with post-therapeutic neurolgia, insterstital cystitis, osteoarthritis, spinal cord injury, cancer and diabetic neuropathy. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Subtype-selective NMDA receptor ligands and the use thereof Inventor(s): Araldi, Gian Luca; (Washington, DC), Bigge, Christopher F.; (Ann Arbor, MI), Cai, Sui Xiong; (Foothill, CA), Guzikowski, Anthony P.; (Eugene, OR), Keana, John F.W.; (Eugene, OR), Lamunyon, Donald; (Tualatin, OR), Lan, Nancy C.; (South Pasadena, CA), Zhou, Zhang-Lin; (Irvine, CA) Correspondence: Fitzpatrick Cella Harper & Scinto; 30 Rockefeller Plaza; New York; NY; 10112; US Patent Application Number: 20010051633 Date filed: February 7, 2001 Abstract: The invention relates to subtype-selective NMDA receptor ligands and the use thereof for treating or preventing neuronal loss associated with stroke, ischemia, CNS trauma, hypoglycemia and surgery, as well as treating neurodegenerative diseases including Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's disease and Down's syndrome, treating or preventing the adverse consequences of the overstimulation of the excitatory amino acids, treating anxiety, psychosis, convulsions, aminoglycoside antibiotics-induced hearing loss, migraine headache, chronic pain, Parkinson's disease, glaucoma, CMV retinitis, urinary incontinence, opioid tolerance or withdrawal, and inducing anesthesia, as well as for enhancing cognition. Excerpt(s): This invention is related to 2-substituted piperidine analogs. The analogs are selectively active as antagonists of N-methyl-D-aspartate (NMDA) receptor subtypes. The invention is also directed to the use of 2-substituted piperidine analogs as neuroprotective agents for treating conditions such as stroke, cerebral ischemia, central nervous system trauma, hypoglycemia, anxiety, convulsions, aminoglycoside antibiotics-induced hearing loss, migraine headaches, chronic pain, glaucoma, CMV retinitis, psychosis, urinary incontinence, opioid tolerance or withdrawal, or neurodegenerative disorders such as lathyrism, Alzheimer's Disease, Parkinsonism and Huntington's Disease. Excessive excitation by neurotransmitters can cause the degeneration and death of neurons. It is believed that this degeneration is in part mediated by the excitotoxic actions of the excitatory amino acids (EAA) glutamate and aspartate at the N-methyl-D-Aspartate (NMDA) receptor. This excitotoxic action is considered responsible for the loss of neurons in cerebrovascular disorders such as cerebral ischemia or cerebral infarction resulting from a range of conditions, such as thromboembolic or hemorrhagic stroke, cerebral vasospasms, hypoglycemia, cardiac arrest, status epilepticus, perinatal asphyxia, anoxia such as from drowning, pulmonary surgery and cerebral trauma, as well as lathyrism, Alzheimer's Disease, Parkinson's Disease and Huntington's Disease. Excitatory amino acid receptor antagonists that block NMDA receptors are recognized for usefulness in the treatment of disorders. NMDA receptors are intimately involved in the phenomenon of excitotoxicity, which may be a critical determinant of outcome of several neurological disorders. Disorders known to be responsive to blockade of the NMDA receptor include acute cerebral ischemia (stroke or cerebral trauma, for example), muscular spasm, convulsive disorders, neuropathic pain and anxiety, and may be a significant causal factor in chronic neurodegenerative disorders such as Parkinson's disease [T. Klockgether, L. Turski, Ann. Neurol. 34, 585593 (1993)], human immunodeficiency virus (HIV) related neuronal injury, amyotrophic lateral sclerosis (ALS), Alzheimer's disease [P.T. Francis, N. R. Sims, A. W. Procter, D. M. Bowen, J. Neurochem. 60 (5), 1589-1604 (1993)] and Huntington's disease. [See S. Lipton, TINS 16 (12), 527-532 (1993); S. A. Lipton, P. A. Rosenberg, New Eng. J. Med. 330 (9), 613-622 (1994); and C. F. Bigge, Biochem. Pharmacol. 45, 1547-1561 (1993) and references cited therein.]. NMDA receptor antagonists may also be used to prevent tolerance to
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opiate analgesia or to help control withdrawal symptoms from addictive drugs (Eur. Pat. Appl. 488,959A). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Tetrahydroisoquinoline-3-carboxylic acid alkoxyguanidines as integrin antagonists Inventor(s): Marder, Victor J.; (Los Angeles, CA), U'Prichard, David C.; (Philadelphia, PA), Wang, Aihua; (Jamison, PA) Correspondence: Sterne, Kessler, Goldstein & Fox Pllc; 1100 New York Avenue, N.W., Suite 600; Washington; DC; 20005-3934; US Patent Application Number: 20020061885 Date filed: October 3, 2001 Abstract: The present invention relates to novel tetrahydroisoquinoline-3-carboxylic acid alkoxyguanidine compounds that are antagonists of alpha V (.alpha.v) integrins, for example.alpha.sub.v.beta.sub.3 and.alpha.sub.v.beta.sub.5 integrins, their pharmaceutically acceptable salts, and pharmaceutical compositions thereof. The compounds may be used in the treatment and/or prevention of pathological conditions mediated by.alpha.sub.v.beta.sub.3 and.alpha.sub.v.beta.sub.5 integrins such as tumor growth, metastasis, restenosis, osteoporosis, inflammation, macular degeneration, diabetic retinopathy, rheumatoid arthritis, sickle cell anemia, and in treatment and/or prevention of central nervous system (CNS) related disorders such as neuronal loss associated with stroke, ischemia, CNS trauma, hypoglycemia, surgery, neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease, adverse consequences of overstimulation of one or more excitatory amino acids, anxiety, convulsions, chronic pain, psychosis, schizophrenia, anesthesia, and opiate tolerance. The compounds have the general formula: 1where R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8, R.sup.9, R.sup.10, m and n are defined herein. Excerpt(s): This application is a continuation-in-part of U.S. patent application Ser. No. 09/921,759, filed Aug. 6, 2001, which claims priority under 35 U.S.C.sctn. 119(e) to U.S. Provisional Patent Application No. 60/223,478, filed Aug. 7, 2000, now abandoned, both of which are incorporated by reference herein in their entirety. The present invention relates to novel tetrahydroisoquinoline-3-car- boxylic acid alkoxyguanidine compounds that are antagonists of alpha V (.alpha.v) integrins, for example.alpha.sub.v.beta.sub.3 and.alpha.sub.v.beta.sub.5 integrins, their pharmaceutically acceptable salts, and pharmaceutical compositions thereof. Integrins are cell surface glycoprotein receptors which bind extracellular matrix proteins and mediate cell-cell and cell-extracellular matrix interactions (generally referred to as cell adhesion events) (Hynes, R. O., Cell 69:11-25 (1992)). These receptors are composed of noncovalently associated alpha (.alpha.) and beta (.beta.) chains which combine to give a variety of heterodimeric proteins with distinct cellular and adhesive specificities (Albeda, S. M., Lab. Invest. 68:414 (1993)). Recent studies have implicated integrins in the regulation of cellular adhesion, migration, invasion, proliferation, apoptosis and gene expression (Albeda, S. M., Lab. Invest. 68:4-14 (1993); Juliano, R., Cancer Met. Rev. 13:25-30 (1994); Ruoslahti, E. and Reed, J. C., Cell 77:477-478 (1994); and Ruoslahti, E. and Giancotti, F. G., Cancer Cells 1:119-126 (1989)). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Therapeutic agent composition and method of use Inventor(s): Tran, Loi H.; (Elk Grove, CA) Correspondence: David R Preston & Associates; 12625 High Bluff Drive; Suite 205; San Diego; CA; 92130; US Patent Application Number: 20030109531 Date filed: November 12, 2002 Abstract: The invention relates to the use of cyclic Prolyl Glycine ("cyclic PG" or "cPG") and analogs and mimetics thereof, as neuroprotective agents for the treatment and or prevention of neurological disorders including but not limited to cerebral ischemia or cerebral infarction resulting from a range of phenomena, such as thromboembolic or hemorrhagic stroke, cerebral basospasms, hypoglycemia, cardiac arrest, status epilepticus, perinatal asphyxia, anoxia such as from drowning, pulmonary surgery, and cerebral trauma, as well as to the treatment and prevention of chronic neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, and Huntington's disease, and as anticonvulsants. Excerpt(s): This application claims benefit of priority to New Zealand provisional patent No. 515432 filed Nov. 13, 2001, and U.S. provisional patent application Serial No. 60/405,909 filed Aug. 26, 2002, and both incorporated by reference herein. Excessive excitation by neurotransmitters can cause the degeneration and death of neurons. It is believed that this degeneration is in part mediated by the excitotoxic actions of the excitotoxic amino acids (EAA) glutamate and aspartate at the N-methyl-D-aspartate (NMDA) receptor, the alpha-amino-3-hydroxy-5-methyl 4-isoxazole proprionic acid (AMPA) receptor, and the kainate receptor. AMPA/Kainate receptors may be referred to jointly as non-NMDA receptors. This excitotoxic action is considered responsible for the loss of neurons in cerebrovascular disorders such as cerebral ischemia or cerebral infarction resulting from a range of conditions, such as thromboembol or hemorrhagic stroke, cerebral vascospasm, hypoglycemia, cardiac drowning, pulmonary surgery, and cerebral trauma, as well as Alzheimer's disease, Parkinson's disease, and Huntington's disease. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
Keeping Current In order to stay informed about patents and patent applications dealing with hypoglycemia, 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 “hypoglycemia” (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 hypoglycemia. You can also use this procedure to view pending patent applications concerning hypoglycemia. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.
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CHAPTER 7. BOOKS ON HYPOGLYCEMIA Overview This chapter provides bibliographic book references relating to hypoglycemia. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on hypoglycemia 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 “hypoglycemia” (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 hypoglycemia: •
Pediatric Nutrition Handbook, Fourth Edition Source: Elk Grove Village, IL: American Academy of Pediatrics. 1998. 833 p. Contact: Available from American Academy of Pediatrics. P.O. Box 927, 141 Northwest Point Boulevard, Elk Grove Village, IL 60009-0927. (800) 433-9016. PRICE: $47.95 (members) plus $6.25 shipping and handling; $52.95 for nonmembers; plus $8.95 shipping and handling. ISBN: 1581100051. Summary: Assessment of nutritional status and providing dietary advice and nutritional support are important and increasingly prominent components of the practice of those who provide health care for infants, children, and adolescents. This handbook serves as a ready desk reference on the nutritional requirements and impact of nutritional status on the health of infants, children, and adolescents. Forty-three chapters cover breastfeeding; formula feeding of term infants; supplemental foods for infants; vitamin and mineral supplement needs of healthy children in the United States; feeding from
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age 1 year to adolescence; adolescent nutrition; the nutritional needs of preterm infants; the recognition and management of pediatric swallowing disorders; energy; proteins; carbohydrate and dietary fiber; fats and fatty acids; calcium, phosphorus, and magnesium; trace elements; vitamins; infant nutrition and the development of gastrointestinal function; parenteral nutrition; enteral nutrition; nutrition and oral health; sports nutrition; community nutrition services for children; current legislation and regulations regarding infant formulas; assessment of nutritional status; failure to thrive; gastrointestinal disease, persistent diarrheal disease, and malabsorption; oral rehydration therapy and posttreatment feeding after enteritis; iron deficiency; inborn errors of metabolism; dietary management of diabetes mellitus; hypoglycemia; hyperlipidemia; obesity in children; food hypersensitivity; nutrition and immunity; nutritional management of children with a chronic illness; nutrition in children with HIV infection; diet in the prevention of cancer or hypertension; food labeling; nutritional aspects of vegetarian diets; fast foods, organic foods and megavitamins; food safety; and new food ingredients. Extensive appendices and a subject index conclude the volume. •
Outsmarting Diabetes: A Dynamic Approach for Reducing the Effects of InsulinDependent Diabetes Source: Minneapolis, MN: Chronimed Publishing. 1994. 247 p. Contact: Available from Chronimed Publishing. P.O. Box 59032, Minnetonka, MN 55459-9686. (800) 848-2793 or (612) 541-0239. Fax (800) 395-3344 or (612) 541-0210. PRICE: $14.95. ISBN: 1565610512. Available from Joslin Publications. One Joslin Place, Boston, MA 02215. (800) 344-4501. Fax (617) 732-2562. PRICE: $14.95. Summary: Based on the results of the Diabetes Control and Complications Trial (DCCT) and the expertise of the Joslin Diabetes Center in Boston, this book explains to readers the benefits of careful diabetes control. Designed to help people with diabetes reduce their risks for complications, the book's 11 chapters address whether or not complications can truly be prevented; intensive insulin management; designing an individualized plan; getting started; maintenance on an intensive plan; meal planning; using multiple daily insulin injections; using insulin pumps; exercise and the intensive plan; pregnancy and intensive diabetes therapy; psychological concerns; and handling problems. Numerous appendices provide information on intensified conventional treatment programs; Ultralenta programs; the use of premeal regular plus bedtime intermediate insulin; the insulin pump; calculating daily volume for insulin pump therapy; exercise guidelines; hyperglycemia; hypoglycemia; products and foods for hypoglycemic reactions; and a sample record book. A brief subject index concludes the volume.
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Understanding Insulin-Dependent Diabetes. 8th ed Source: Denver, CO: Barbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences Center. Children's Diabetes Foundation at Denver. 1995. 253 p. Contact: Available from Guild of the Children's Diabetes Foundation at Denver. 777 Grant Street, Suite 302, Denver, CO 80203. (800) 695-2873 or (303) 863-1200. Fax (303) 863-1122. PRICE: $10.00. The book is also available at http://www.uchsc.edu/misc/diabetes/bdc.html. Summary: Designed for the families of children with diabetes, this book uses the Pink Panther character to explain diabetes and its care. The book begins by explaining the importance of education in diabetes, what diabetes is, and the causes of diabetes. Urine
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ketone testing, hypoglycemia, blood sugar testing, insulin, nutrition, blood sugar control, complications, sick day and surgery management, intensive diabetes management, research, ketonuria, and ketoacidosis are explained in depth. Many chapters of the book discuss the social and emotional aspects of coping with diabetes, including family concerns, responsibilities of children at different ages, the challenges of being a teenager with diabetes, school, babysitters, vacations, and camp. 3 appendices and a subject index conclude the book. Charts, tables, and illustrations are used throughout the book. The book is written at a 10th to 12th grade level. •
Uncomplicated Guide to Diabetes Complications. 2nd ed Source: Alexandria, VA: American Diabetes Association. 2002. 294 p. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800)232-3472. E-mail:
[email protected]. Website: www.diabetes.org. PRICE: $16.95; plus shipping and handling. ISBN: 58040133. Summary: Diabetes mellitus can result in many complications, but many of them can be prevented. This book explains to patients how early testing, new medical treatments, and improvements in diabetes control can prevent or slow the development of complications. Each complication is discussed, including symptoms, medical treatments, and self care approaches, in nontechnical language. Twenty chapters cover acute complications (diabetic ketoacidosis or DKA, and hyperosmolar hyperglycemic state or HHS), hypoglycemia (low blood glucose levels), foot problems, eye disease (diabetic retinopathy), heart disease, cholesterol and other blood fats, stroke, hypertension (high blood pressure), nephropathy (kidney disease), peripheral vascular disease, peripheral neuropathy (nerve disease), autonomic neuropathies, gastrointestinal complications, infection and diabetes, diabetes and skin, psychosocial complications, men's sexual health, women's sexual health, oral health, and prevention strategies. This edition includes information on the discoveries and recommendations from the recently completed Diabetes Prevention Program, which linked improved diet and exercise with a slow-down in the development of diabetes and of its complications. One appendix lists medical tests, including recommended scheduling for those tests. A brief description of the activities and resources of the American Diabetes Association is included. A subject index concludes the book.
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Atlas of Clinical Endocrinology Source: Malden, MA: Blackwell Science, Inc. 2000. 212 p. 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: $131.95. ISBN: 0632043997. Summary: Diabetes mellitus is among the most common endocrine disorders, affecting about 7 percent of the United States population. This medical atlas provides clinical photographs, charts and figures, with lengthy captions for each, to support the diagnosis and management of patients with diabetes. Fifteen chapters cover the regulation of insulin secretion and islet cell function, the mechanisms of insulin action, the consequences of insulin deficiency, type 1 diabetes, the management and prevention of complications in type 1 diabetes mellitus, the pathogenesis of type 2 noninsulin dependent diabetes, the management and prevention of diabetic complications, insulin resistance, hypoglycemia, mechanisms of hyperglycemic damage in diabetes, eye complications of diabetes, diabetes and the kidney, diabetic neuropathies (nerve
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disease), secondary forms of diabetes, and obesity. A detailed subject index concludes the volume. This atlas is one in a series of five volumes on clinical endocrinology. •
Getting the Most Out of Diabetes Camp: A Guide for Parents and Kids Source: Alexandria, VA: American Diabetes Association. 2002. 106 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: $14.95 plus shipping and handling. ISBN: 1580401422. Summary: For many children, attending a diabetes camp is a life-changing experience. These camps provide a safe place where kids are surrounded by people with diabetes, where everyone else is doing the same things to manage their illness and have a good quality of life. This book helps youngsters with diabetes and their parents learn about diabetes camps, decide whether to go, and then to choose the right diabetes camp. The book offers nine chapters: why choose diabetes camp over other types of camps, how to determine if a child is ready for camp, selecting the most appropriate camp, the application process, packing tips, what to expect at camp, homesickness, traditional camps, and how to evaluate a camp experience after it is over. The authors include numerous quotes from children and parents, and practical suggestions in each chapter. The book includes four appendices: a list of diabetes camps, a sample application packet, a sample scholarship application, and the warning signs of hypoglycemia (low blood glucose) and hyperglycemia (high blood glucose). A subject index concludes the book.
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Challenging Cases in Endocrinology Source: Totowa, NJ: The Humana Press, Inc. 2002. 421 p. Contact: Humana Press, Inc. 999 Riverview Dr., Suite 208 Totowa, NJ 07512. (973) 2561699. Fax (973) 256-8341. E-mail:
[email protected] PRICE: $145.00, plus shipping and handling. ISBN:0896039145. Summary: In medicine, the difficult cases can yield valuable insights because they force physicians to think a little harder when making a diagnosis and to be creative when treating the patient. In this textbook, distinguished clinician-scientists describe in concise studies their most difficult cases and reveal what they did, how they did it, and why. The cases cover a wide range of medical problems, including pituitary and thyroid tumors, hypopituitarism, hyper and hypo thyroidism, metabolic bone disease, Cushing's syndrome, adrenal insufficiency, cancer, diabetes, and hypoglycemia (low blood glucose). Other cases involve disorders of female reproduction, of water balance and lipoprotein metabolism, of puberty, and of growth and development. Each case study reviews how the patient was managed, details the reasons why various tests and treatments (many only recently available) were carried out, and provides references to ensure that these novel methodologies can be easily translated into the endocrine specialist's daily practice. Two chapters are particularly relevant for diabetes: Type 1 Diabetes Mellitus (Chapter 16) and Type 2 Diabetes Mellitus (Chapter 17). The volume concludes with a detailed subject index.
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Managing Your Diabetes Without Insulin Source: Boston, MA: Joslin Diabetes Center. 1997. 18 p.
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Contact: Available from Joslin Diabetes Center. One Joslin Place, Boston, MA 02215. (800) 344-4501. Fax (617) 732-2562. Website: www.joslin.org. PRICE: $3.50; plus shipping and handling. Item number: JDC 260. Summary: Individuals with type 2 diabetes can make some insulin but do not use it properly; this type of diabetes often can be managed without insulin injections. This booklet offers diabetes management strategies for readers with type 2 diabetes who do not use insulin. The booklet covers the symptoms of uncontrolled diabetes, the causes of diabetes, the diabetes care team, why it is important to maintain blood glucose (sugar) at healthful levels, food and nutrition guidelines (the role of carbohydrates, dietary fiber, portion control, sugar intake), the role of exercise, target heart rate, weight management, blood glucose testing (SMBG), recordkeeping, medication, the complications of poorly managed diabetes, how to cope with low blood glucose (hypoglycemia) and high blood glucose (hypertension) episodes, foot care, sick days, traveling with diabetes, support groups, and behavior modification strategies. The booklet offers practical, everyday tips for patients. 2 figures. 6 tables. •
Practical Insulin: A Handbook for Prescribers Source: Alexandria, VA: American Diabetes Association. 2002. 60 p. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. E-mail:
[email protected]. Fax: (770) 4429742. Website: www.diabetes.org. PRICE: $7.95; plus shipping and handling. ISBN: 580401538. Summary: Insulin therapy is a medical necessity for all patients with type 1 diabetes and the many patients with type 2 diabetes who cannot reach their glycemic goals without insulin therapy. This pocket handbook to prescribing insulin is designed to help primary care providers handle ever-increasing numbers of patients with diabetes. The handbook covers patient selection, insulin choices, insulin character, insulin absorption, mixing insulins, insulin regimens, insulin for type 1 patients, insulin for type 2 patients, troubleshooting (patient resistance to starting insulin, weight gain, fasting hyperglycemia, hypoglycemia, and hypoglycemia unawareness), patient SMBG (self monitoring of blood glucose) records, and patient education. Lengthy appendices cover endogenous insulin action, insulin storage, insulin potency, additives, insulin delivery, insulin pumps, and determining insulin to carbohydrate ratio. The handbook concludes with a brief description of the American Diabetes Association and its contact information (www.diabetes.org).
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Joslin's Diabetes Mellitus. 13th ed Source: Malvern, PA: Lea and Febiger. 1994. 1068 p. Contact: Available from Williams and Wilkins. 351 West Camden Street, Baltimore, MD 21201-2436. (800) 638-0672 or (410) 528-4223. Fax (800) 447-8438 or (410) 528-8550. PRICE: $139.00 plus shipping and handling. ISBN: 0812115317. Also available from Joslin Publications. One Joslin Place, Boston, MA 02215. (800) 344-4501. Fax (617) 7322562. PRICE: $139.00 plus shipping and handling. Summary: The 13th edition of this standard textbook covers diabetes pathophysiology, diagnosis, and treatment focusing on the team approach. Fifty-six chapters are presented in seven sections: basic mechanisms; the definition and pathogenesis of diabetes; obesity and lipiprotein disorders; the treatment of diabetes mellitus; onset of the complications of diabetes; the clinical aspects of diabetes complications; and
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hypoglycemia and islet-cell tumors. Each chapter is written by experts in the field and includes numerous references. A detailed subject index concludes the volume. •
Type I Diabetes: Etiology and Treatment Source: Totowa, NJ: Humana Press. 2003. 608 p. Contact: Available from Humana Press. 999 Riverview Drive, Suite 208, Totowa, NJ 07512. (973) 256-1699. Fax (973) 256-8341. E-mail:
[email protected]. Website: www.humanapress.com. PRICE: $130.50; plus shipping and handling. ISBN: 896039315. Summary: The increasing incidence of diabetes worldwide has prompted a rapid growth in the pace of scientific discovery and clinical understanding of this disease. In this book, well-recognized physicians and researchers review the latest thinking about the causes of type 1 diabetes and the best approaches to treating both its acute and chronic complications. The book includes 32 chapters in four sections: etiology (cause), treatment, special management issues, and long-term complications. Specific topics include epidemiology, genetics, prediction and prevention of type 1 diabetes, beta-cell destruction by autoimmune processes, the metabolic basis of insulin secretion, prevention and correction of hypoglycemia, nonautoimmune forms of diabetes, diabetic ketoacidosis, insulin regimens, relationship between metabolic control and complications, insulin delivery systems and glucose sensors, patient and family education, nutritional management, management of diabetes in very young children, children, adolescents, hypoglycemia, pregnancy, surgery for the patient with type 1 diabetes, diabetic retinopathy (eye disease), diabetic nephropathy (kidney disease), diabetic peripheral and autonomic neuropathy (nerve disease), the diabetic foot, atherosclerosis in type 1 diabetes, cutaneous (skin) complications, infection and diabetes, pancreas transplantation, islet transplantation, beta cell replacement therapy, and islet growth factors. Each chapter concludes with a list of references and a subject index concludes the textbook.
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My Sister Rose Has Diabetes Source: Santa Fe, NM: Health Press. 1997. 32 p. Contact: Available from Health Press. P.O. Box 1388, Santa Fe, NM 87504. (800) 6432665. Fax (505) 983-1733. E-mail:
[email protected]. Website: www.healthpress.com. PRICE: $8.95 (paperback). ISBN: 09291732779. Summary: This book addresses many of the difficult issues facing children who have diabetes and their families. It demonstrates how manageable the disease can be and reduces the devastation of those concerned. The book is written from the perspectives of both Rose, a ten year old girl who has diabetes, and her twelve year old brother. Rose's parents were surprised that she was diagnosed with diabetes; in fact, the book notes that 90 percent of children with diabetes do not have a family history of the disease. Topics include coping, self-monitoring blood glucose, injecting insulin, meal planning, hypoglycemia and hyperglycemia symptoms, sick days, working with a patient care team, and recordkeeping. Rose points out that the three things that she needs to balance are food, insulin, and exercise. Drawings painted with watercolor are included on nearly every page. A glossary explains terms of anatomy, diabetes, and treatment in children's wording. (AA-M).
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101 Medication Tips for People with Diabetes Source: Alexandria, VA: American Diabetes Association. 1999. 122 p.
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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: $14.95 plus shipping and handling. ISBN: 1580400329. Order number 483301. Summary: This book answers 101 of the most commonly asked questions about diabetes and medications to help readers become active members of their health care team, maximize their diabetes management, and stay well. Questions in chapter one provide general information on medications used to treat diabetes. Chapter two focuses on how to get the most out of oral medications. The third chapter deals with common side effects of oral medications, including gastrointestinal and liver problems, weight gain, lactic acidosis, and hypoglycemia. Questions in chapter four provide general information on the use of insulin in type 2 diabetes. This is followed by a chapter that explains how to get the most out of insulin therapy. Chapter six identifies the common side effects of insulin, including weight gain. Questions in the next chapter deal with the meditations used to treat complications, including nonprescription analgesics, tricyclic antidepressants, capsaicin cream, angiotensin converting enzyme inhibitors, laxatives, and calcium channel blockers. This is followed by chapters that answer questions about the effect of medications on diabetes; the use of nonprescription medications such as aspirin, cold and allergy medications, herbal supplements, weight loss products, and vitamin and mineral supplements; and common drug interactions that occur with diabetes medications. The final chapter answers miscellaneous questions. The book also includes a glossary and an index. •
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; 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.
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Hypo-Hyper: 101 Short Stories About Diabetes Source: Richmond, VA: Endocrine and Diabetes Management Center. 1996. 106 p. Contact: Available from Endocrine and Diabetes Management Center. 7231 Forest Avenue, Suite 103, Richmond, VA 23226. PRICE: $15.00. Summary: This book is a collection of short stories about the experiences of patients with diabetes. The book includes 24 topics related to hypoglycemia (low blood glucose), and 14 topics around ketoacidosis. Each of the stories briefly relates (in a paragraph or
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two) a patient's duration of diabetes, presenting problem, treatment, and outcome. The stories are prefaced by an index with which readers can find experiences that fit the circumstances they are interested in. The authors do not make any judgements about each of the stories, merely presenting the facts as they were reported to them. The stories are meant to be a reflection of the real world of diabetes. Topics addressed include brittle diabetes, patient-doctor interrelationships, the elderly, exercise, family issues, injury or death, blood glucose meters, driving motor vehicles, neuroglycopenia, problems at night, patient noncompliance, pregnancy, insulin pumps, severe hypoglycemic reactions, stress and emotional issues, IDDM, NIDDM, hypoglycemic unawareness, newly diagnosed diabetes, ketoacidosis in pregnancy, complications, diabetes and Addison's disease, medical mismanagement, pump user errors, and self advocacy. •
Instructions for Patients. 5th ed Source: Philadelphia, PA: W.B. Saunders Company. 1994. 598 p. Contact: Available from W.B. Saunders Company. Book Order Fulfillment, 6277 Sea Harbor Drive, Orlando, FL 32887-4430. (800) 545-2522. Fax (800) 874-6418. PRICE: $49.95. ISBN: 0721649300 (English); 0721669972 (Spanish). Summary: This book is a compilation of instructions for patients, published in paperback format. Each fact sheet provides information in three sections: basic information, including a description of the condition, frequent signs and symptoms, causes, risk factors, preventive measures, expected outcome, and possible complications; treatment, including general measures, medication, activity guidelines, and diet; and when to contact one's health care provider. Fact sheets are available on diabetes topics including: diabetes feet and skin problems; diabetes hypoglycemia; insulin-dependent diabetes; and noninsulin-dependent diabetes. The fact sheets can be photocopied and distributed to patients as a reinforcement of verbal instructions and as a teaching tool. The book is available in English or Spanish.
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Living a Healthy Life With Chronic Conditions: Self-Management of Heart Disease, Arthritis, Stroke, Diabetes, Asthma, Bronchitis, Emphysema and Others Source: Palo Alto, CA: Bull Publishing Company. 1994. 296 p. Contact: Available from Bull Publishing Company. P.O. Box 208, Palo Alto, CA 943020208. (800) 676-2855 or (415) 322-2855. Fax (415) 327-3300. E-mail:
[email protected]. PRICE: $14.95. ISBN: 0923521283. Summary: This book is a complete self-management guide for people with chronic diseases. The authors focus on day-to-day living skills, in the context of the specific chronic diseases, including heart disease, arthritis, stroke, diabetes, asthma, bronchitis, and emphysema. General topics include the psychological aspects to self-management; finding resources; smoking and quitting; understanding common symptoms; using one's mind to manage symptoms; exercising for fun and fitness; exercising for flexibility and strength; exercising for endurance; exercising tips for people with specific chronic diseases; the importance of communication; durable powers of attorney for health care; eating well; and managing medications. The chapter on diabetes covers diabetes and its causes; maintaining an appropriate blood glucose level; symptoms of hyperglycemia and hypoglycemia; dietary management; exercise; insulin injections; oral medications; emotions; self-monitoring of blood glucose and urine; the complications of diabetes; and diabetes resources. Each chapter includes limited references and a subject index concludes the volume.
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Diabetes Problem Solver Source: Alexandria, VA: American Diabetes Association. 1999. 511 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: $19.95 for members; plus shipping and handling. ISBN: 1570400091. Summary: This book is a reference guide that helps people who have diabetes identify and prevent the most common diabetes-related problems they encounter on a daily basis. The book is divided into two major sections. The first section consists of a series of flowcharts to help readers decide what they need to do about a particular condition or symptom. Flowcharts focus on arm and hand pain, back pain, blurry vision, chest pain, confusion, convulsions or seizures, difficulty breathing, dizziness, dry skin, eating disorders, emotional problems, emotional changes in women, feeling tired, fever, foot problems, headache, hyperglycemia, hypoglycemia, injection site problems, and intestinal problems. Other flowcharts deal with leg and foot pain, loss of consciousness, muscular weakness, nausea, numbness and tingling, pain or discomfort in women, palpitations, problems with the mouth, problems with blood glucose in women, sexual problems in men and women, skin discoloration, skin lesions, skin rashes and itchy skin, sleeping problems, stomach pain, sweating, swelling, thickening of the skin, urinary problems, vision problems, and vomiting. The second section provides more detailed information about many of the problems people who have diabetes face. Solutions are provided for monitoring and testing problems; hypoglycemia and hyperglycemia problems; insulin delivery and oral medication problems; circulation, neuropathy, kidney, vision, gastrointestinal, infection, foot, and skin problems; men's, women's, and children's problems; eating, exercise, and weight problems; lifestyle problems; coping problems; discrimination and insurance problems; and other medical problems. Each section provides the reader with information on the symptoms of the condition, who is at risk and what risk the particular condition poses for the reader, what the reader's immediate course of action should be, treatment in a medical setting, and how to prevent the condition from developing. The reader may use the book in two ways. If the reader knows he or she has a particular condition or wants more information, he or she can go straight to the second section and look up the condition. The reader may use the book as a guide to possible conditions that may be causing symptoms by referring to the flowcharts in the first section. The book also includes a glossary, resources, and an index. 6 figures. 5 tables.
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Difficult Diabetes Source: Malden, MA: Blackwell Science, Inc. 2001. 308 p. 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: $154.95. ISBN: 0632053240. Summary: This book is intended for diabetes specialists and endocrinologists who want to keep abreast of the most topical and controversial aspects of diabetes management. Four sections cover diagnostic and screening issues; management issues in type 2 diabetes; management issues in type 1 diabetes; and general diabetes issues such as managing coexisting disease and employment and driving restrictions. Specific topics including screening for diabetes, patient selection, impaired glucose tolerance, gestational diabetes, microalbuminuria (microscopic protein in the urine), obesity, oral
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hypoglycemic agents, the use of insulin in type 2 diabetes, foot ulcers, management in adolescents, brittle diabetes, hypoglycemia unawareness, intensive diabetes management, insulin pumps, transplantation of the pancreas, erectile dysfunction, and hypertension (high blood pressure). Each chapter concludes with a list of references and the text concludes with a subject index. •
Core Curriculum for Diabetes Education. 4th ed.: (Volume 2) Diabetes Management Therapies Source: Chicago, IL: American Association of Diabetes Educators (AADE). 2001. 306 p. Contact: Available from American Association of Diabetes Educators. AADE Member Service Center, 100 W. Monroe Street, Suite 400, Chicago, IL 60603. (800) 338-3633. Fax (312) 424-2427. Website: www.diabeteseducator.org. PRICE: Individual volume $45.00 for members and $60.00 for nonmembers; complete 4-volume set $149.95 for members and $199.95 for nonmembers; plus shipping and handling. ISBN: 1881876063 (Volume 2); 1881876098 (4-volume set). Summary: This book is the second in a series of four texts that make up a Core Curriculum, designed primarily to help educators prepare for the Certified Diabetes Educator (CDE) exam. In addition, these books can be used as a diabetes educator's reference source for diabetes education and management. This second volume, on diabetes management therapies, covers medical nutrition therapy (MNT) for diabetes, exercise, pharmacologic (drug) therapies, monitoring, pattern management of blood glucose, insulin pump therapy and carbohydrate counting for pump therapy, hypoglycemia, and coping with illness and surgery. Each chapter lists the learning objectives for that chapter, presents information in outline and bulleted format, summarizes the key educational considerations, offers self review questions and questions for discussion, presents an illustrative case report, and concludes with a list of references. A post-test and the answers to the post-test questions are appended to each chapter. The volume concludes with a subject index.
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Beating the Blood Sugar Blues Source: Alexandria, VA: American Diabetes Association. 2001. 159 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: $12.95 plus shipping and handling. ISBN: 1580400485. Summary: This book offers first hand knowledge from two doctors who have more than 100 years of combined experienced with the day-to-day balancing act of blood glucose (sugar) and diabetes. The authors, both of whom have type 1 diabetes, share their own stories as well as those of over 40 of their patients. The book includes 20 chapters that cover an overview of hypoglycemia (low blood glucose levels), the risks associated with high and low blood glucose levels, monitoring blood glucose levels (SMBG), monitoring blood levels over time (glycosylated hemoglobin levels), treating low blood glucose at home, adjusting insulin to avoid hypoglycemia, using a meal plan to control blood glucose, the impact of exercise on blood glucose, handling low blood glucose at school, teenagers and the blood sugar blues, sex and pregnancy and their impact on hypoglycemia, sleep, driving or flying safely, traveling and hypoglycemia, alcohol and hypoglycemia, prescription drugs and hypoglycemia, the effects of hypoglycemia on nerves and vision, psychological insights, losing awareness of hypoglycemia, and managing one's own diabetes. The book concludes with a subject index.
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Medical Advisor Home Edition: The Complete Guide to Alternative and Conventional Treatments Source: Alexandria, VA: Time-Life Books. 1997. 960 p. Contact: Available from Time-Life Books. 400 Keystone Industrial Park, Dunsmore, PA 18512. PRICE: $20.00. ISBN: 0783552505. Summary: This book offers information about 300 health problems, ranging from relatively benign conditions to serious diseases. The book includes symptom charts that name several related problems and help readers decide which ailment entry to look up. Ailment entries provide a more complete list of symptoms, plus guidelines to discern whether the condition is potentially serious or requires a doctor's attention. Each entry describes the ailment and how it affects the body. Next, the entry outlines the underlying causes of the ailment and the tests and procedures a doctor may use to confirm the diagnosis. The treatment segment presents conventional and alternative recommendations for solving the problem or alleviating the symptoms. Most ailment entries conclude with advice on preventive measures that can be used to maintain health. Alternative treatments described include bodywork, acupuncture and acupressure, herbal therapies, homeopathy, lifestyle changes, and nutrition and diet. The book begins with a section on emergency medicine, and includes a visual diagnostic guide, an atlas to the body, a medicine chest section (describing herbs, homeopathic remedies, and over the counter drugs), a glossary, a subject index, a bibliography, and a list of health associations and organizations. Topics related to diabetes include atherosclerosis, glaucoma, hypoglycemia, kidney disease, obesity, and sexual dysfunction. A section specific to diabetes is also included. The book is illustrated with line drawings and full color photographs.
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Diabetes: Clinical Science in Practice Source: Cambridge, England: Cambridge University Press. 1995. 492 p. Contact: Available from Cambridge University Press. 40 West 20th Street, New York, NY 10011-4211. (800) 872-7423. Fax (212) 691-3239. PRICE: $155.00. ISBN: 0521450292. Summary: This book presents an overview of recent scientific advances in diabetes research and highlights the role of these developments in advancing clinical practice. Chapters in part one focus mainly on the causes of diabetes. Topics include the regulation of insulin secretion, the regulation of insulin gene transcription, the molecular structure of insulin, insulin receptors, the role of protein phosphorylation in insulin action, glucose transport mechanisms, and glucose homeostasis. Other chapters deal with the epidemiology, genetics, and etiology of type 1 diabetes; the epidemiology and genetics of type 2 diabetes; islet amyloid polypeptide and amyloid in the islets of Langerhans; and the characteristics and clinical significance of primary insulin resistance. The second part of the book focuses on the epidemiology of the complications of diabetes. Complications include macrovascular disease, diabetic neuropathy, diabetic foot infections, ocular complications, and diabetic nephropathy. Other chapters discuss the personal, social, and economic impact of diabetic complications; mortality among persons with diabetes; and diabetic complications as they relate to glycation, the sorbitol pathway, and proteinuria. In addition, chapters examine pharmacological approaches to type 2 diabetes, insulin therapy, hypoglycemia, strategies for preventing type 1 diabetes, treatment of early diabetic renal disease, pancreatic transplantation in humans with diabetes mellitus, management of type 1 and type 2 diabetes, and the psychosocial aspects of diabetes care. Each chapter contains
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numerous tables, figures, and references. An appendix provides sample patient rules for insulin adjustment and an index concludes the book. •
Practical Psychology for Diabetes Clinicians: How to Deal with the Key Behavioral Issues Faced by Patients and Health Care Teams Source: Alexandria, VA: American Diabetes Association. 1996. 200 p. Contact: Available from American Diabetes Association. Order Fulfillment Department, P.O. Box 930850, Atlanta, GA 31193-0850. (800) 232-6733. Fax (404) 442-9742. PRICE: $19.95 (members); $24.95 (nonmembers). ISBN: 0945448732. Summary: This book presents guidelines for diabetes clinicians in handling the behavioral issues faced by patients with diabetes. The book is divided into four areas of clinically important behavioral issues: recommendations specific to developmental (age related) and family factors; guidelines concerning treatment regimen factors; recommendations for handling complex and chronic behavioral issues; and guidelines for preventing special problems with the patient-physician relationship, emotional responses to diagnosis, patient 'burnout' and physician 'burnout.' Within each of these four areas are guidelines for handling some of the most stubborn and serious problems facing diabetes clinicians and their patients; these problems including hypoglycemia, lack of motivation, lack of exercise, excess weight, and smoking. A subject index concludes the book.
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American Diabetes Association Guide to Raising a Child with Diabetes. 2nd ed Source: Alexandria, VA: American Diabetes Association. 2000. 165 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: $16.95 plus shipping and handling. ISBN: 1580400272. Summary: This book presents up to date information on diabetes to help parents and other family members care for a child who has diabetes. The book begins with a chapter that explains the causes of type 1 diabetes, identifies the signs and symptoms of diabetes, and discusses the management of blood glucose levels. The next chapter focuses on caring for the child who has diabetes. Topics include new thinking about treating children with diabetes, the role of health care providers, and ways to keep a child's best interests a top priority. Chapter three discusses the use of insulin to manage diabetes, focusing on insulin types, insulin dosages, insulin administration, site rotation, insulin delivery devices, needle disposal, insulin adjustment, and self injection. This is followed by a chapter that explains blood glucose testing. Topics include determining the number of times per day to test blood glucose, recording blood glucose test results, making sure a blood glucose meter is accurate, testing urine for glucose and ketones, helping a child test regularly, and understanding the glycated hemoglobin test. The fifth chapter deals with meal planning, focusing on planning balanced meals; using exchanges and carbohydrate counting to plan meals; helping a child accept meal planning; coping with schedule changes, holidays, and parties; and eating out. The next chapter offers guidelines for playing games and sports safely. This is followed by a chapter that explains how to prevent and treat hypoglycemia, hyperglycemia, and ketoacidosis and how to handle sick days and infections. Chapter eight deals with diabetes care during various stages of development, focusing on care of infants, preschoolers, school age children, and adolescents. The final chapter offers advice for living with diabetes, focusing on budgeting, traveling, solving the day to day challenges
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of diabetes, coping with diabetes, and asking for help. The book provides problem solving examples and easy to read tables throughout. In addition, the book includes a glossary, a list of resources, and an index. 44 figures. 2 tables. •
Diabetes Sourcebook. 3rd ed Source: Detroit, MI: Omnigraphics. 2003. 621 p. Contact: Available from Omnigraphics. 615 Griswold Street, Detroit, MI 48226. (800) 234-1340. Fax (800) 875-1340. Website: www.omnigraphics.com. ISBN: 780806298. Summary: This book provides information for people seeking to understand the risk factors, complications, and management of type 1 diabetes, type 2 diabetes, and gestational diabetes. The book offers 67 chapters in seven sections: diabetes types and diagnosis; lifestyle and related diabetes management concerns; exercise and nutrition for diabetes management; medication management of diabetes; complications of diabetes; treatment of end stage renal disease (ESRD); and diabetes-related research and statistics. Specific topics include risk factors, impaired glucose tolerance (IGT), insulin resistance, HbA1c (glycosylated hemoglobin) testing, blood glucose testing, urine testing, SMBG (self monitoring of blood glucose), non-invasive blood glucose monitors, preventing complications, how stress affect diabetes, alternative therapies for diabetes, exercise, exchange lists, carbohydrate counting, eating at restaurants, insulin administration and dosage, oral medications, amputation, kidney disease (diabetic nephropathy), diabetic retinopathy (eye disease), diabetic neuropathy (nerve disease), gastroparesis (reduced motility of stomach contents), hypoglycemia (low blood glucose levels), hyperglycemia (high blood glucose levels), erectile dysfunction (ED formerly called impotence), research advances in diabetes, and diabetes in ethnic and racial groups. The book includes a glossary of related terms, information about locating financial help for diabetes care, and a list of resources, including organizations, recipes and cookbooks.
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Mayo Clinic on Managing Diabetes Source: Rochester, MN: Mayo Clinic. 2001. 194 p. Contact: Available from Mayo Clinic Health Information. 200 First Street, S.W., Fifth Floor Centerplace Building, Rochester, MN 55905. (800) 430-9699. Website: www.mayoclinic.com. PRICE: $14.95 plus shipping and handling. ISBN: 1893005062. Summary: This book provides practical and easy to understand information on controlling diabetes and preventing complications of the disease. Part one provides facts about diabetes. Topics include types of diabetes, the signs and symptoms of diabetes, the risk factors for diabetes, and the criteria and tests for diagnosing diabetes. In addition, the issue of diabetic complications is addressed, focusing on hypoglycemia, diabetic hyperosmolar syndrome, diabetic ketoacidosis, neuropathy, nephropathy, retinopathy, heart and blood vessel disease, and increased risk of infection. Part two deals with the components involved in controlling the disease. Chapters discuss monitoring blood glucose, eating a healthy diet, getting daily exercise, and maintaining a healthy weight. Part three examines medical therapies for managing diabetes. Chapters provide information on the use of insulin to manage type 1 and type 2 diabetes; the use of sulfonylureas, meglinitides, biguanides, alpha glucosidase inhibitors, thiazolidinediones, and drug combinations to manage type 2 diabetes; and pancreas and islet cell transplantation as possible cures for diabetes. Part four addresses issues related to living well with diabetes. One chapter focuses on important tests every person who has diabetes should be getting, including the glycosylated hemoglobin test,
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lipid tests, the serum creatinine test, and the urine microalbumin test. Another chapter discusses self care issues, including having annual physical examinations, visiting a dentist regularly, caring for feet, avoiding smoking, monitoring blood pressure, and managing stress. A third chapter explores sexual health issues for both men and women. Topics include the affect of the menstrual cycle and menopause on blood glucose, hormone replacement therapy, pregnancy, and impotence. Each chapter concludes with a question and answer section. The book also includes a list of additional resources. 17 figures. 1 table. •
Diabetes: Questions You Have, Answers You Need. Revised ed Source: Allentown, PA: People's Medical Society. 1997. 191 p. Contact: Available from Independent Publishers Group. Order Department, 814 N. Franklin Street, Chicago, IL 60610. (800) 888-4741 or (312) 337-0747. Fax (312) 337-5985. E-mail:
[email protected]. PRICE: $12.95. ISBN: 1882606531. Summary: This book provides readers with a 'consumer's guide' to managing diabetes. The author emphasizes that, while diabetes is incurable, with proper medical treatment and a great deal of self management, most people with diabetes can live normal length lives with little or no restrictions on their lifestyles. The author hopes that the information in the book can help empower people with diabetes and encourage them to become and remain active participants in their own health care. The first chapter introduces the basics of Type I and Type II diabetes (insulin-dependent and noninsulindependent, respectively), including risk factors for diabetes, impaired glucose tolerance, secondary diabetes, and gestational diabetes. The next chapter focuses on the use of insulin in Type I diabetes, including insulin pumps, jet injectors, and insulin pens. The chapter on Type II diabetes covers insulin resistance, heredity, obesity, diet, oral therapy, insulin therapy, combination therapy, and new treatment options. Chapter Four covers the short term complications of diabetes, including hypoglycemia, ketoacidosis, and hyperosmolar or nonketotic coma; and the longterm complications, including eye problems, nephropathy (kidney disease), cardiovascular complications, neuropathy, and foot problems. The final chapter emphasizes self management, discussing issues including the self monitoring of blood glucose (SMBG), nutrition, exercise, foot care, dental care, smoking, children and diabetes, pregnancy and diabetes, and aging. The book concludes with a glossary, a selected bibliography, and a subject index. 47 references.
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Insulin Pump Therapy Book: Insights from the Experts Source: Sylmar, CA: MiniMed Technologies. 1995. 162 p. Contact: Available from MiniMed Technologies. 12744 San Fernando Road, Sylmar, CA 91342. (800) 933-3322 or (818) 362-5958. Fax (818) 364-2246. PRICE: $19. ISBN: 0964783703. Summary: This book provides readers with a comprehensive overview of the insulin pump. The authors hope to help establish insulin pump therapy as a cost-effective mode of intensive diabetes management that not only facilitates normalized blood glucose, but also makes it feasible for people living with diabetes to experience the most normal lifestyle possible. Thirteen chapters the benefits of insulin pump therapy; candidate selection; initiating pump therapy; establishing and verifying basal rates; bolus and supplemental insulin; counting carbohydrates; pattern analysis and recordkeeping; everyday management; exercise and the pump; preventing diabetic ketoacidosis (DKA);
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hypoglycemia and its prevention; and pump therapy in preconception and pregnancy. A subject index concludes the volume. •
Diabetes Source: New York, NY: Times Books. 1997. 283 p. Contact: Available from Times Books. 201 East 50th Street, New York, NY 10022. (800) 733-3000. PRICE: $14.00. ISBN: 0812923200. Summary: This book provides the latest information on type 1 and type 2 diabetes. After explaining what diabetes is and differentiating between type 1 and type 2, the book discusses the diagnosis. The role of various diabetes treatment team members, including the diabetologist, the diabetes nurse educator, the dietitian, and other specialists, are described as well. One chapter provides general nutritional guidelines and explains meal planning systems for managing diabetes, including healthy food choices, the exchange system, and the carbohydrate counting system. Next, an overview of insulin and insulin therapy for type 1 and type 2 diabetes are presented. Other chapters focus on incorporating exercise into a treatment program; hypoglycemia, including its symptoms and treatment; the diagnosis and treatment of various complications, including eye disease, kidney disease, neuropathy, large blood vessel disease, and foot problems; and pregnancy. Also noted are special considerations for type 2 diabetes, and the Diabetes Control and Complications Trial, which followed 1,441 people with type 1 diabetes for 10 years and found that tight blood glucose control could prevent or delay complications and slow the progression. The book concludes with an index. 6 figures. 1 table.
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Core Curriculum for Diabetes Education. 3rd ed Source: Chicago, IL: American Association of Diabetes Educators. 1998. 901 p. Contact: Available from American Association of Diabetes Educators. 100 West Monroe Street, 4th Floor, Chicago, IL 60603-1901. (800) 338-3633 or (312) 424-2426. Fax (312) 4242427. PRICE: $95.00 for AADE members; $135.00 for nonmembers. ISBN: 1881876047. Summary: This book provides the most up-to-date information for diabetes educators so that they can help people with diabetes to become effective decision makers for their own diabetes care. The first section addresses the issue of education, focusing on the program design and educational methods used to help patients learn about diabetes. The next section examines psychosocial issues, including psychological assessment, behavior changes, and psychological disorders. The third section explains the pathophysiology of the diabetes disease state. The following section describes therapies that will help people with diabetes make self directed behavior changes to improve their overall diabetes management or nutritional status. Topics include nutrition, exercise, pharmacologic therapies, self-monitoring of blood glucose, and monitoring of metabolic control by the health care team. The fifth section examines blood glucose management, focusing on pattern management; hyperglycemia; hypoglycemia; illness and surgery; and skin, foot, and dental care. The sixth section discusses the impact of diabetes during each stage of the life cycle, focusing on diabetes in children, adolescents, pregnant women, and the elderly. This is followed by a section on the complications of diabetes, including eye disease, neuropathy, nephropathy, and macrovascular disease. The final section discusses the importance of research and outcomes. Chapters include case studies, self-review questions, and lists of suggested readings. The book concludes with continuing education post-test questions for each chapter and an index. 41 figures. Numerous tables. Numerous references.
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Diabetes Care for Babies, Toddlers, and Preschoolers: A Reassuring Guide Source: Somerset, NJ: John Wiley and Sons, Inc. 1999. 92 p. Contact: Available from John Wiley and Sons. One Wiley Drive, Somerset, NJ 08875. (800) 225-5945 or (732) 469-4400. Fax (732) 302-2300. E-mail:
[email protected]. Website: www.wiley.com. PRICE: $14.95 plus shipping and handling. ISBN: 0471346764. Summary: This book serves as a guide for parents who have a young child with newly diagnosed diabetes. The book helps parents find a balance between good diabetes management and normal life. Chapter one focuses on the emotional impact of the diagnosis on the family. Topics include dealing with the loss, coping with family members and friends, taking action, and helping siblings cope with the diagnosis. Chapter two describes child development in terms of size and growth, eating patterns, and sleep and activity patterns. Chapter three addresses diabetes issues in young children, including using insulin, giving insulin injections, dealing with food, monitoring blood glucose, and testing for urine ketones. Chapter four explains how to prevent, detect, and treat hypoglycemia. Chapters five and six address special issues relevant to infants, toddlers, and preschoolers, including the impact of diabetes on these age groups. Chapter seven examines day care and preschool issues. The book also includes experiences and advice from other parents of children who have diabetes. The book concludes with a list of helpful resources and an index.
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Churchill's Pocketbook of Diabetes Source: New York, NY: Harcourt Health Sciences. 2000. 316 p. Contact: Available from Harcourt Health Sciences. Foots Cray High Street, Sidcup, Kent DA14 5HP, United Kingdom. 020 8308 5700. Fax 020 8308 5702. E-mail:
[email protected]. PRICE: $24.95 plus shipping and handling. ISBN: 0443061181. Summary: This book serves as a resource for health care workers who are not diabetes specialists but who are in regular contact with people who have diabetes. The book offers guidance on the daily management of these patients. The book begins with a chapter on the key biochemical defects of diabetes and recent changes in classification. Chapter two focuses on the diagnosis and initial management of diabetes. Topics include the clinical presentation of diabetes, the diagnostic criteria for diabetes, the history and physical examination, the influence of comorbidity, the psychological impact of diabetes, the aims of treatment, the relationship between glycemic control and complications, the assessment of glycemic control, the principles of education in diabetes, and the organization and economics of diabetes care. The next chapter discusses the management of diabetes, focusing on nutrition therapy, smoking cessation or reduction, physical exercise, oral antidiabetic agent therapy, insulin therapy, and pancreatic and islet cell transplantation. The focus of the fourth chapter is on the acute metabolic complications of diabetes, including hypoglycemia, diabetic ketoacidosis, diabetic hyperosmolar nonketotic syndrome, and lactic acidosis. The fifth chapter describes the complications of diabetes, including ocular, kidney, nerve, foot, macrovascular, cutaneous, musculoskeletal, and connective tissue problems; hypertension; diabetic dyslipidemia; and infection. The final chapter addresses special topics, including diabetes in children, adolescents, the elderly, and pregnant women; intercurrent illness; surgery and other invasive procedures; and social and legal aspects. The book also presents evidence based boxes providing the rationale underlying treatment decisions. 19 figures. 16 plates. Numerous tables. 74 references.
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Diabetes for Dummies Source: Foster City, CA: IDG Books Worldwide, Inc. 1999. 371 p. Contact: Available from IDG Books Worldwide, Inc. 919 E. Hillsdale Blvd., Suite 400, Foster City, CA 94404-2112. (800) 762-2974 or (416) 293-8464. Website: www.idgbooks.com. PRICE: $19.99 plus shipping and handling. ISBN: 076455154X. Summary: This book serves as a state of the art guide to diabetes management. Part one focuses on dealing with the onset of diabetes. Topics include the emotional and psychological consequences of the diagnosis of diabetes; the diagnosis itself; and the symptoms, causes, and prevention of type 1 and type 2 diabetes. Part two explains how diabetes affects the body, focusing on acute and chronic complications. Topics include the symptoms, causes, and treatment of hypoglycemia, ketoacidosis, and hyperosmolar syndrome; the prevention of diabetic nephropathy, retinopathy, and neuropathy; and the prevention of heart disease, peripheral and cerebrovascular disease, diabetic foot disease, and skin diseases. In addition, readers are given information about some sexual problems related to diabetes and the problems of a diabetic pregnancy. Part three presents information on all the tools available to treat diabetes. Readers are told about the kinds of tests they and their doctor should be doing to maintain health, the dietary changes and physical activity that are needed to control blood glucose, and the way to get the most from oral hypoglycemic agents and insulin. Other topics include the role of various professionals in diabetes care and the use of knowledge to improve quality of life. Part four addresses special diabetes related considerations for infants, children, adolescents, young adults, and the elderly. Other topics include occupational and insurance problems, new diabetes care devices and medications, and treatments that do not work. Part five presents 10 ways to prevent or reverse the effects of diabetes, dispels 10 myths about diabetes, and identifies 10 ways to obtain help from others. Part six consists of appendices that present recipes, exchange lists, websites, and a glossary. 8 figures. 10 tables.
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Handbook of Diabetes Source: Malden, MA: Blackwell Science, Inc. 1992. 125 p. 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]. PRICE: $39.95. ISBN: 0632028882. Summary: This book summarizes some of the information contained in its parent volume, the Textbook of Diabetes. This handbook is devoted to the daily treatment and surveillance of diabetes and its more common problems and is written for health professionals with an interest in diabetes who work outside the hospital setting. Twenty-four chapters cover the diagnosis and classification of diabetes; clinical problems of insulin-dependent and noninsulin-dependent diabetes mellitus (IDDM or Type I, and NIDDM or Type II, respectively); the causes of diabetes; diabetic control and diabetes management; the treatment of IDDM and of NIDDM; hypoglycemia; diabetic ketoacidosis; nonketotic hyperosmolar coma; microvascular disease; everyday living with diabetes; drugs and diabetes; diabetic eye disease; diabetic neuropathies; diabetic nephropathy; cardiac, macrovascular and hypertensive disease in people with diabetes; foot problems; skin care and problems in diabetes; sexual function in men with diabetes; and the role of various members of the diabetes health care team. Each chapter includes numerous full-color tables, charts, and photographs. A subject index concludes the volume.
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Family and Friends' Guide to Diabetes: Everything You Need to Know Source: New York, NY: John Wiley and Sons, Inc. 2000. 282 p. Contact: Available from John Wiley and Sons, Inc. Distribution Center, 1 Wiley Drive, Somerset, NJ 08875-1272. (800) 225-5945 or (732) 469-4400. Fax (732) 302-2300. E-mail:
[email protected]. Website: www.wiley.com. PRICE: $14.95 plus shipping and handling. ISBN 0471348015. Summary: This book uses a question and answer format to provide the family and friends of people who have diabetes with information on the disease so that they can be understanding and supportive to those who have diabetes. Chapter one presents facts about diabetes. The chapter explains what diabetes is and what a normal blood glucose level is; describes type 1, type 2, and gestational diabetes; and discusses the causes of these types of diabetes. Other topics include diagnosing and treating diabetes, monitoring blood glucose levels, and understanding complications. In addition, the chapter dispels common myths about diabetes. The second chapter focuses on the management of low blood glucose. Topics include the causes, symptoms, and treatment of hypoglycemia. The next chapter deals with meal planning. The chapter teaches readers what people who have diabetes are advised to eat, what exchanges and carbohydrate counting are, and how to modify meals to make them lower in fat and sodium. In addition, readers learn how to plan menus and identify the different types of sugar found naturally in foods. Chapter four reviews the effect illness has on diabetes. The chapter describes the causes, symptoms, and treatment of hyperglycemia and diabetic ketoacidosis and offers tips on how to help people who have diabetes during an illness. This is followed by a chapter that focuses on planning special occasions. The chapter provides tips and ideas on how to make holidays and celebrations fun and healthy for everyone. Other topics include simple courtesies to keep in mind to make special times less stressful for those who have diabetes or others who are watching what they eat. Chapter six offers guidelines for creating a work environment that supports healthy lifestyle habits and is diabetes friendly. The chapter helps readers assess their workplace and organizational culture to identify any barriers that could create diabetes self care challenges and discusses the creation of an emergency plan for hypoglycemia. In addition, the chapter explains why diabetes is a legal disability and how current laws prevent workplace discrimination. This is followed by a chapter that helps readers assess the impact of diabetes on their lives, teaches them positive coping skills, and suggests ways to create a supportive environment for them and the person who has diabetes. Chapter eight focuses on promoting healthy habits at home. The chapter helps readers learn how change occurs and to plan for it, assess readiness to change an unhealthy behavior, and help someone trying to change or break an unhealthy habit. The final chapter offers guidelines for building positive relationships and friendships. 4 appendices. Numerous references.
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Medical Management of Pregnancy Complicated by Diabetes. 3rd ed Source: Alexandria, VA: American Diabetes Association. 2000. 176 p. Contact: Available from American Diabetes Association (ADA). Order Fulfillment Department, P.O. Box 930850, Atlanta, GA 31193-0850. (800) 232-6733. Fax (770) 4429742. Website: www.diabetes.org. PRICE: $39.95 plus shipping and handling. ISBN: 1580400132. Summary: This book, which is part of the American Diabetes Association's Clinical Education Series, provides health professionals with protocols that have resulted in healthy infants in pregnancies complicated by type 1, type 2, or gestational diabetes. The
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first section focuses on prepregnancy counseling and management of women with preexisting diabetes or previous gestational diabetes. The next section discusses contraceptive methods, including oral contraceptives, the norplant system, barrier methods, intrauterine devices, the rhythm method, and permanent sterilization. This is followed by a section that examines the psychological impact of diabetes and pregnancy. Topics include the response to pregnancy in women with preexisting diabetes, the response to a diagnosis of gestational diabetes, long term adaptation, personality types and individualizing treatment, pregnancy crises, and the importance of a team approach and a support system. The fourth section focuses on blood glucose monitoring. Topics include glycosylated hemoglobin measurements in pregnancy for women with preexisting or gestational diabetes, self monitoring of blood glucose and urine ketones, and medical tests to evaluate maternal status in women with preexisting or gestational diabetes. The next section offers guidelines for managing morning sickness with dietary remedies, insulin adjustments, and medical management. The sixth section discusses nutritional management during pregnancy in women with preexisting diabetes. Topics include patient responsibility; the nutrient needs of pregnancy; diet and eating habits; vitamin and mineral supplementation; calorie level; weight gain; meal planning; recordkeeping; use of sodium, caffeine, and artificial sweeteners; the management of hypoglycemia; and postpartum nutritional management. Section seven focuses on the use of insulin during pregnancy in women with preexisting diabetes. Topics include metabolic alterations during normal gestation, therapeutic insulin use, dosage adjustment, insulin during labor and delivery, postpartum insulin requirements, and oral hypoglycemic agents. The next section describes diagnostic tests and methods of fetal surveillance, including ultrasonography, alpha fetoprotein testing, genetic testing, fetal monitoring, and amniocentesis. The ninth section discusses gestational diabetes, focusing on epidemiology, screening, diagnosis, nutritional management, insulin therapy, exercise, and obstetric management. Section ten addresses the issue of neonatal care of infants of women with diabetes. Topics include perinatal mortality and morbidity, resuscitation, nursery care, and long term followup. The final section discusses postpartum followup of women with gestational diabetes. The book includes an index and resources for health care professionals. 3 figures. 39 tables. Numerous references. •
My Doctor Says I Have a Little Diabetes Source: Garden City Park, NY: Avery Publishing Group. 1997. 138 p. Contact: Available from Avery Publishing Group. 120 Old Broadway, Garden City Park, NY 11040. (800) 548-5757 or (516) 741-2155. Fax (516) 742-1892. E-mail:
[email protected]. Website: www.averypublishing.com. PRICE: $9.95 plus shipping and handling. ISBN: 0895298600. Summary: This book, which is written in easy to understand language, serves as a guide to understanding and controlling type 2 diabetes. The book begins with a chapter that provides basic information on diabetes and diabetes care. Topics include the symptoms of diabetes, the types of diabetes, risk factors for diabetes, diagnostic tests for diabetes, common misconceptions about diabetes, and the management of the emotional aspects of diabetes. Each of the remaining chapters examines a specific aspect of diabetes care, including monitoring blood levels, following an appropriate diet, exercising, using medications, managing high and low blood glucose levels, preventing complications, and handling special situations. The chapter on glucose monitoring offers guidelines for selecting a monitor and checking blood glucose levels. The chapter on diet presents the latest goals and guidelines for the nutritional management of type 2 diabetes; explains
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how protein, carbohydrates, fats, and other nutrients affect diabetes; provides meal planning options that will make eating an enjoyable experience; and offers tips for handling special situations. The chapter on exercise discusses some of the advantages of following a program of regular exercise, helps readers choose a program suited to their needs, and offers advice about how to begin an exercise program. The chapter on medication discusses the different diabetes medications, medication interactions and precautions, and the effects that many prescription and over the counter medications have on diabetes. The chapter also presents information about mixing and injecting various types of insulin. The chapter on dealing with high and low blood glucose levels presents the causes, symptoms, and associated problems of hyperglycemia and hypoglycemia. Guidelines for treating these problems are also provided. The chapter on the prevention of complications reviews symptoms and prevention of the complications associated with diabetes, including high blood pressure; atherosclerosis; eye disorders; kidney disease; and foot and lower leg, autonomic nervous system, skin, and sexual problems. The final chapter on special situations covers the special care needed on sick days and when traveling. The book also includes a list of resources and provides tables for converting glucose, cholesterol, and triglyceride levels from milligram per deciliter to millimoles per liter. 3 figures. 8 tables. 28 references. •
Diabetes Is Not a Piece of Cake Source: Lake Oswego, OR: Lincoln Publishing Incorporated. 1994. 281 p. Contact: Available from Lincoln Publishing, Inc. P.O. Box 1499, Lake Oswego, OR 97035. (800) BOOKS-4-U or (503) 699-1000. Fax (503) 699-2000. PRICE: $14.95 plus $1.80 shipping and handling (as of 1995). ISBN: 1884929753. Summary: This book, written for the family, friends, colleagues and classmates of people with diabetes, provides easily understandable, comprehensive information about diabetes and how it is managed. Written primarily in a question and answer format, the book covers the history of diabetes; how diabetes affects the body physically; different types of diabetes treatments; the costs of managing diabetes; diabetes complications; hypoglycemia and its treatment; hyperglycemia and its prevention; the diabetes diet; cooking for people with diabetes; dining out with someone with diabetes; exercise; pregnancy in women with diabetes; diabetes in children and adolescents; and the psychosocial and emotional factors that diabetes can generate. The book also provides 24 pages of recipes, a glossary of terms, removable poster pages on dealing with emergencies, a list of resources, and a subject index. The book is illustrated throughout with humorous cartoon figures.
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Do Your Level Best: Start Controlling Your Blood Sugar Today Source: Bethesda, MD: National Diabetes Outreach Program (NDOP), National Diabetes Information Clearinghouse (NDIC). September 1995. 60 p. 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: Single copy free; bulk orders available to health professionals; contact NDIC for current availability status. Also available at http://www.niddk.nih.gov/. Summary: This booklet helps people with newly diagnosed diabetes learn how to take care of their diabetes and how to prevent complications of the disease. Topics include an introduction to how diabetes affects the body and the types of diabetes; regular diabetes
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care, including proper food, nutrition, medications, monitoring (blood glucose testing), and recordkeeping; what to do when blood glucose levels are high (hyperglycemia) or low (hypoglycemia); the impact diabetes can have on the heart and blood vessels, the eyes, the kidneys, the nervous system, the gums and teeth, and the feet; taking care of diabetes in special circumstances, including sick days, travel, and during pregnancy; and where to get additional information and help. The booklet features a back pocket with various brochures, including those on diabetes and periodontal disease, diabetic eye disease, and diabetes research, and a recordkeeping form for readers to keep track of their diabetes management activities. •
Living with Type 2 Diabetes Source: Hamilton, Ontario, Canada: Hamilton Civic Hospitals. 1997. 43 p. Contact: Available from Robert Panchyson, Education Department, 3LN, Hamilton Health Sciences Corp. General Site, 237 Barton Street East, Hamilton, Ontario, Canada, L8L 2X2. (905) 527-4322, ext. 6615. Fax (905) 527-1941. PRICE: Contact directly for current price. Summary: This booklet is written primarily for elderly patients with diabetes. It is written at a grade 4 to 6 reading level. The booklet defines diabetes and blood glucose and covers the impact of foods on blood glucose levels, insulin, how insulin works, type 2 diabetes, weight and meal plans, exercise and activity levels, low blood glucose (hypoglycemia) and its treatment, prevention of hypoglycemia, high blood glucose (hyperglycemia), diabetes medications, alcohol and diabetes medications, and diabetes complications. The booklet presents clear practical suggestions for managing various aspects of diabetes self care, and is illustrated with simple line drawings to help readers comprehend the topics. The 1997 revision of the English-language version (other language versions have not yet been revised) includes additional information about cholesterol, blood pressure and oral medications. The booklet is available in English, Spanish, French, Italian, Polish, or Portuguese. A Hindi version is expected.
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Taking Diabetes to School. 2nd ed Source: Valley Park, MO: JayJo Books, LLC. 1998. 26 p. Contact: Available from JayJo Books, LLC. P.O. Box 213, Valley Park, MO 63088-0213. (800) 801-0159 or (314) 861-1331. PRICE: $11.95. ISBN: 1891383000. Summary: This children's book presents basic information about diabetes from the perspective of a young boy with the disease. The book, designed to be read aloud in the classroom, focuses on the school experiences of a child with diabetes. The book discusses adherence to scheduled meal plans, especially during class; testing for blood glucose levels; the problem of hypoglycemia; emergency identification tags; and sports and exercise. The book concludes with 10 tips for teachers who have students with diabetes in the classroom. The book is illustrated in full color with drawings of the child's various activities.
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What You Need to Know About Diabetes: A Short Guide Source: Boston, MA: Joslin Diabetes Center. 1999. 60 p. Contact: Available from Joslin Diabetes Center. One Joslin Place, Boston, MA 02215. (800) 344-4501 or (508) 583-3240. Fax (617) 732-2562. Website: www.joslin.harvard.edu. PRICE: $11.50 each; plus shipping and handling. Order number JDC210.
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Summary: This guide provides people who have diabetes with information on the basics of diabetes self care. The guide begins with a chapter that explains normal metabolism and the impact of diabetes on body functioning, identifies the short-and long-term risks of high blood sugar, defines low blood sugar, and offers self care tips. This is followed by a chapter that explains how to use good nutrition practices to care for diabetes. Topics include eating the right amount and kind of food at the right time; developing a meal plan; and making healthy food choices by limiting fatty foods, consuming high fiber food, using less salt, replacing sugar with artificial sweeteners, and limiting alcohol consumption. The chapter also offers tips for eating out and developing healthy eating habits and provides examples of food choices from various food groups. Chapter three provides guidelines for using exercise to care for diabetes, focusing on starting an exercise plan and preventing a low blood sugar reaction. This is followed by a chapter that focuses on the use of medications to care for diabetes. The chapter provides information on insulin, offers tips for drawing up and injecting a single or mixed dose of insulin, and presents suggestions for taking care of insulin and syringes. In addition, the chapter explains how oral diabetes medications work, presents guidelines for taking oral diabetes medications, and summarizes tips for using oral medications that are currently available. Chapter five focuses on the monitoring of blood glucose. Topics include the steps involved in checking blood for sugar and urine for ketones. The sixth chapter discusses special problems, including hyperglycemia, diabetic ketoacidosis, hyperglycemic hyperosmolar nonketotic state, and hypoglycemia. Remaining chapters outline sick day rules; offer foot care tips; present guidelines for avoiding eye, kidney, nerve, heart and blood vessel, and foot damage; and provide suggestions for living with diabetes. •
Diabetes: Clinical Management Source: New York, NY: Churchill Livingstone, Inc. 1990. 289 p. Contact: Available from Churchill Livingstone, Inc. 650 Avenue of the Americas, New York, NY 10011. (212) 206-5000. PRICE: $49.95. ISBN: 0443022739. Summary: This guide to diabetes is designed for those health care practitioners who deliver most of the front-line diabetes care: general practitioners and specialist nurses. Thirty-three chapters are divided into five sections: the new patient, including considerations such as choosing an insulin regimen, the importance of diabetes control, and how diabetes affects the patient; resources, including setting up a diabetes service, recordkeeping, and the role of diabetes specialist nurse; special patients, including children, pregnant women, and the elderly; special situations, including ketoacidosis, intensive insulin therapy, hypoglycemia, and managing diabetes during surgery; and complications, including eye problems, foot problems, hypertension, and infections. A subject index completes the volume.
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Handbook of Diabetes, Second Edition Source: Malden, MA: Blackwell Science, Inc. 1999. 220 p. 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: $60.95. ISBN: 0632055049. Summary: This handbook covers a wide spectrum of information on diabetes mellitus. The handbook includes an introduction and 31 topical chapters: the history of diabetes, diagnosis of diabetes, classification, public health aspects, normal physiology of insulin
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secretion and action, the epidemiology and etiology of type 1 diabetes, the epidemiology and etiology of type 2 diabetes, other types of diabetes, assessing control in diabetes, the management of type 1 diabetes, the management of type 2 diabetes, diabetic ketoacidosis and hyperosmolar non-ketotic coma, hypoglycemia (low blood glucose levels), control and complications, diabetic eye disease (retinopathy), diabetic nephropathy (kidney disease), diabetic neuropathy (nerve disease), hyperlipidemia (high levels of blood fats) in diabetes, hypertension (high blood pressure) in diabetes, macrovascular disease in diabetes, the diabetic foot, sexual problems in diabetes, gastrointestinal problems in diabetes, the skin in diabetes, psychological and psychiatric problems in diabetes, some intercurrent problems (exercise, drugs, infection, surgery), pregnancy and diabetes, diabetes in children, diabetes in the elderly, lifestyle considerations (driving, employment, smoking, travel), and the organization of diabetes care. The handbook design includes information presented in small chunks, with numerous color illustrations, charts, and photographs to make the information more accessible. A detailed subject index concludes the book. •
Diabetes Mellitus: A Practical Handbook. 6th ed Source: Palo Alto, CA: Bull Publishing. 1995. 200 p. Contact: Available from Bull Publishing. P.O. Box 208, Palo Alto, CA 94302-0208. (415) 322-2855. Fax (415) 327-3300. PRICE: $12.95 plus shipping and handling. ISBN: 0923521313. Summary: This handbook explains diabetes in simple language and diagrams. Topics include the etiology of diabetes mellitus; hyperglycemia and hypoglycemia; blood sugar levels; diet and nutrition; self monitoring of blood glucose; urine testing; ketones and ketoacidosis; insulin and insulin storage; injection techniques; oral diabetes medications; laboratory tests; exercise; sick days; personal hygiene, including skin care and foot care; stress and emotions; traveling with diabetes; complications; and research. Additional sections discuss resources and organizations where peole can seek more information; a bibliography; meal planning forms; and a time schedule.
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Therapy for Diabetes Mellitus and Related Disorders. 3rd ed Source: Alexandria, VA: American Diabetes Association. 1998. 487 p. Contact: Available from American Diabetes Association (ADA). Order Fulfillment Department, P.O. Box 930850, Atlanta, GA 31193-0850. (800) 232-6733. Fax (770) 4429742. Website: www.diabetes.org. PRICE: $39.95 plus shipping and handling. ISBN: 0945448945. Summary: This handbook focuses on the treatment of problems that are of importance in the management of people with diabetes mellitus. The book attempts to help health professionals apply major advances in health care to their patients. Topics include the diagnosis and classification of diabetes mellitus, genetic counseling for type 1 diabetes, gestational diabetes mellitus, the management of pregnant women who have diabetes, antepartum and intrapartum obstetric care, neonatal problems and their management, type 1 diabetes and diabetic ketoacidosis in children, psychosocial adjustment in children who have type 1 diabetes, psychosocial aspects in adults, diabetic ketoacidosis and hyperosmolar hyperglycemic nonketotic syndrome in adults, and lactic acidosis. Other topics include the role of diabetes education in patient management; self monitoring of blood glucose; the rationale for management of hyperglycemia; medical nutrition therapy; pharmacological treatment of obesity; exercise; oral hypoglycemic agents such as sulfonylureas, repaglinide, metformin, alpha glucosidase inhibitors, and
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thiazolidinediones; insulin treatment; insulin pump therapy; combination therapy for hyperglycemia; and diabetes complications. In addition, the book discusses surgery and anesthesia in people with diabetes, geriatric patient care, hypoglycemia in patients who have type 1 diabetes, insulin allergy and insulin resistance, drugs and hormones that increase blood glucose levels, diabetic dyslipidemia, antihypertensive therapy, cutaneous disorders associated with diabetes mellitus, infections, visual loss, ocular complications, drug induced renal dysfunction, diabetic nephropathy, chronic kidney disease, painful or insensitive lower extremity, mononeuropathy and amyoradiculopathy, gastrointestinal disturbances, and bladder dysfunction. Final topics include erectile dysfunction, female sexual disorders, postural hypotension, sudomotor dysfunction and dark vision, cardiac denervation syndrome, noninvasive cardiac testing, angina and congestive heart failure, myocardial infarction, peripheral vascular disease, and foot ulcers and infections. The book includes an index. Numerous figures. Numerous tables. Numerous references. •
Pediatric Nutrition Handbook. 3rd ed Source: Elk Grove Village, IL: American Academy of Pediatrics. 1993. 472 p. Contact: Available from American Academy of Pediatrics. P.O. Box 927, 141 Northwest Point Boulevard, Elk Grove Village, IL 60009-0927. (800) 433-9016. PRICE: $47.95 (members) plus $6.25 shipping and handling; $52.95 for nonmembers; plus $8.95 shipping and handling. ISBN: 0910761388. Summary: This handbook serves as a ready desk reference on the nutritional requirements and impact of nutritional status on the health of infants, children, and adolescents. Thirty-five chapters cover breastfeeding; formula feeding of term infants; supplemental foods for infants; vitamin and mineral supplement needs of healthy children in the United States; feeding from age 1 year to adolescence; adolescent nutrition; the nutritional needs of preterm infants; energy; proteins; carbohydrate and dietary fiber; fats and fatty acids; calcium, phosphorus, and magnesium; trace elements; vitamins; infant nutrition and the development of gastrointestinal function; parenteral nutrition; nutrition and oral health; community nutrition services for children; current legislation and regulations regarding infant formulas; assessment of nutritional status; failure to thrive; gastrointestinal disease, chronic diarrhea, and malabsorption; oral fluid therapy and posttreatment feeding after enteritis; iron deficiency; inborn errors of metabolism; diabetes mellitus; hypoglycemia; hyperlipidemia; obesity; food hypersensitivity; nutrition and infection; diet in the prevention of cancer or hypertension; nutritional aspects of vegetarian diets; fast foods, organic foods, and megavitamins; and food additives. Extensive appendices and a subject index conclude the volume.
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Your Child Has Diabetes: A Parents Guide for Managing Diabetes in Children Source: Atlanta, GA: Pritchett and Hull Associates, Inc. 2002. 40 p. Contact: Available from Pritchett and Hull Associates, Inc. 3440 Oakcliff Road, N.E., Suite 110, Atlanta, GA 30340. (800) 241-4925. Website: www.p-h.com. PRICE: $3.25; plus shipping and handling. Summary: This handbook was written to teach parents of children newly diagnosed with diabetes the basics about diabetes and its management. The booklet begins by reminding parents that it may take some time to learn about diabetes and its management, so not to be too discouraged at first. Topics covered include glucose and how the body uses glucose for energy; the two most common types of diabetes; diabetes
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from the child's perspective; the multi-pronged approach to diabetes care, including food, exercise, insulin, oral medicines, and checking blood glucose levels; the members of the typical patient care team; eating healthy meals and snacks; meal planning, diabetes exchanges, and carbohydrate counting; the food pyramid (slightly modified for diabetes); insulin, including injections, insulin pumps, and self monitoring of blood glucose, or SMBG; coping with blood glucose problems, including hyperglycemia (high blood glucose levels) and hypoglycemia (low blood glucose levels); complications of diabetes; and coping with diabetes in school. The booklet is illustrated with colorful, cartoon drawings and includes spaces for parents to individualize the information with their child's goals, the health care providers' telephone numbers, and management strategies. The booklet concludes with a list of resource organizations through which parents can obtain additional information. •
Insulin-Dependent Diabetes in Children, Adolescents and Adults: How to Become an Expert on Your Own Diabetes Source: Uddevalla, Sweden: Becton Dickinson and Company. 1998. 268 p. Contact: Available from Becton Dickinson and Company. Becton Dickinson Division, 1 Becton Drive, Franklin Lakes, NJ 07417-1884. (201) 847-6800. Fax (201) 847-6692. PRICE: $29.00; plus shipping and handling. ISBN: 9163062615. Also available from www.amazon.com and Piara Publishing. Turkosv 12, S-451 62 Uddevalla, Sweden. +46 522 66 93 66. E-mail:
[email protected]. Summary: This illustrated book provides people with the practical information they need to take good care of their diabetes. The book begins by describing the anatomy of the digestive system and explaining how the healthy body works. This is followed by sections that focus on self care; the symptoms and treatment of hypoglycemia and hyperglycemia; insulin treatment; insulin requirements; injection technique; injection aids such as indwelling catheters, automatic injectors, and jet injectors; the insulin pump; the side effects of insulin treatment; the adjustment of insulin doses; temporary and permanent changes to insulin doses; and urine and blood testing. Other sections focus on diet, the use of dietary sweeteners, the consumption of candy and ice cream, weight control, eating disorders, physical exercise, stress, sick days, active and passive smoking, alcohol consumption, pregnancy, social issues, travel, associated diseases, and complications. Several sections focus on research efforts, including research addressing the issue of whether better blood glucose control can lessen the risk of complications and research concerning equipment improvements, the cause of diabetes, and alternative modes of insulin administration. Remaining sections deal with psychological issues, needle phobia, and well known persons who have diabetes. The book includes a glossary, an index, and a reading list. 433 references.
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My Own Type 1 Diabetes Book Source: West Vancouver, BC: Grandma Sandy. 1999. 37 p. Contact: Available from Grandma Sandy. 5742 Westport Court, West Vancouver, BC V7W 2X9. Also available from Amazon.com. PRICE: $10.00 plus shipping and handling. ISBN: 0968667201. Summary: This illustrated book serves as a tool and a reference for children who have type 1 diabetes and their families and caregivers. The book uses simple text and visual imagery to demystify type 1 diabetes. The book begins by explaining how people get diabetes and what diabetes is. This is followed by a discussion of the need for people who have diabetes to balance their diet, exercise, and insulin level. Other topics include
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doing blood glucose checks, eating appropriate foods, injecting insulin, using an insulin pump, exercising, and dealing with hyperglycemia and hypoglycemia. The book includes blank pages for recording notes and reminders, lists reference books for further reading and websites that give additional information, and identifies items for a type 1 diabetes kit. •
Teenagers with Type 1 Diabetes: A Curriculum for Adolescents and Families Source: Alexandria, VA: American Diabetes Association. 2000. [31 p.]. Contact: Available from American Diabetes Association (ADA). Order Fulfillment Department, P.O. Box 930850, Atlanta, GA 31193-0850. (800) 232-6733. Fax (770) 4429742. Website: www.diabetes.org. PRICE: $39.95 plus shipping and handling. ISBN: 158040054X. Summary: This illustrated guide presents a curriculum, based on materials developed for use in the Adolescent Clinic Project, that provides adolescents who have diabetes with a model for making decisions that affect both their lives and their diabetes and teaches adolescents to use problem solving skills to make adjustments to their treatment program based on the results of their blood glucose monitoring. The book is organized into five modules. The first module provides some information about making choices. The second module introduces all of the basic ideas and tools involved in diabetes care. The remaining three modules focus on special issues of decision making and adjusting diabetes treatment plans, including adjusting insulin dosage, planning meals, and exercising. Each module has five sections for health care professionals and two sections for adolescents. The professional sections present learning objectives, guidelines for teen and parent groups, a prequiz, and a postquiz. The adolescent sections provide an overview of the module and its goals and present module information. A final section provides guidelines that can be used with each of the modules. Each guideline offers ideas on special situations such as handling sick days, treating hypoglycemia, using glucagon, getting better results using blood sugar testing, keeping track of blood sugar and insulin, making permanent insulin dose changes, counting carbohydrates, choosing fast foods, determining a target heart rate, selecting exercise snacks, and decreasing insulin dose for extended exercise.
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Keep Yourself Healthy at Home: A Guide for Adults with Diabetes Source: South Deerfield, MA: Channing L. Bete Co., Inc. 2000. 60 p. Contact: Available from Channing L. Bete, Co., Inc. 200 State Road, South Deerfield, MA 01373-0200. (800) 628-7733. Fax (800) 499-6464. PRICE: $3.50 each; plus shipping and handling; quantity discounts available. Order number 97915. Summary: This illustrated handbook provides adults who have diabetes with information on health care. Section one provides general information about health care, the prevention of health problems, and the use of diabetes and general medications. Section two discusses specific problems and their treatment, focusing on allergies, appendicitis, asthma; back pain; bites and stings; bronchitis; bruises, cuts, and scrapes; burns and sunburns; chest pain; colds, flu, and cough; constipation; diarrhea; dizziness and fainting; fever; foot and leg problems; headaches; heartburn; mouth problems; nausea and vomiting; sexual concerns; sexually transmitted diseases; skin problems; sprains and strains; urinary tract infections; and vaginitis. Section three focuses on conditions of special concern for people who have diabetes, including heart disease and stroke and eye, kidney, and nerve diseases. Section four explains how to deal with
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hypoglycemia and hyperglycemia and provides space for writing down emergency numbers and other emergency information. •
Annual Review of Diabetes 2002 Source: Alexandria, VA: American Diabetes Association. 2002. 284 p. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. E-mail:
[email protected]. Fax: (770) 4429742. Website: www.diabetes.org. PRICE: $49.95 plus shipping and handling. Summary: This issue of the Annual Review of Diabetes includes twenty-one research articles in three categories: epidemiology and pathogenesis, treatment, and complications. Specific topics include neurovascular dysfunction in type 2 diabetes; fatty acid metabolism in the etiology (cause) of type 2 diabetes; diabetes, impaired fasting glucose, and elevated HbA1c levels in adolescents; projection of diabetes burden through 2050; autoimmune diabetes; high familial risk and genetic susceptibility in early onset childhood diabetes; fasting versus postload glucose levels; influence of intensive diabetes treatment on body weight and composition of adults with type 1 diabetes; interventions to improve the management of diabetes in primary care, outpatient, and community settings; evidence-based nutrition principles and recommendations for the treatment and prevention of diabetes and related complications; select vitamins and minerals in the management of diabetes; biological complementary therapies (botanical products in diabetes); effect of metformin in pediatric patients with type 2 diabetes; pump therapy for children; gene and cell-replacement therapy in type 1 diabetes; the prevalence of comorbid depression in adults with diabetes; preventing cardiovascular complications of type 2 diabetes by lipid management; diabetic ketoacidosis and hyperglycemic hyperosmolar syndrome; the barrier of hypoglycemia; and the treatment of hypertension in adult patients with diabetes. Each article concludes with a list of references.
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Caring for Young Children Living With Diabetes: Professional Manual Source: Boston, MA: Joslin Diabetes Center. 1996. 125 p. Contact: Available from Joslin Publications. One Joslin Place, Boston, MA 02215. (800) 344-4501. Fax (617) 732-2562. PRICE: $5.95. ISBN: 1879091151. Summary: This manual for health care providers reviews the basics of multidisciplinary diabetes care for young children (age 8 and under) who have insulin-dependent diabetes (IDDM). Sections include current theories in the etiology and pathogenesis of IDDM; the 'team concept' of diabetes management; management strategies to balance insulin, meals, and physical activity, and to provide realistic goals for blood glucose monitoring to achieve safe glycemic control in this population; normal growth and development issues of young children, and how normal developmental tasks and temperaments may make diabetes management difficult; strategies for diabetes crisis management, including sick days, diabetic ketoacidosis (DKA) and severe hypoglycemia; current diabetes research; and the Joslin Diabetes Center's Young Children's Program, a model of comprehensive diabetes care for the family of the young child with IDDM. The manual concludes with appendices and a subject index. (AA-M).
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Children with Diabetes: A Resource Guide for Schools Source: Rensselaer, NY: New York State Health Department. 1999. 100 p.
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Contact: Available from New York State Health Department. Distribution Center, 11 4th Ave., Rensselaer, NY 12144. Fax (518) 465-0432. E-mail:
[email protected]. Website: www.health.state.ny.us. PRICE: Single copy free, also can be found at www.health.state.ny.us/nysdoh/consumer/diabetes/resource/families.htm. Summary: This manual serves as a diabetes resource guide for New York State school personnel. The manual presents an overview of the governor's initiative for people with diabetes. This is followed by an American Diabetes Association (ADA) position statement on the care of children with diabetes in school and day care settings and ADA recommendations for diabetes classification, testing, and diagnosis. The next section provides general information about diabetes. Topics include the symptoms and types of diabetes, nutrition, physical activity, blood glucose monitoring, the symptoms and treatment of hyperglycemia and hypoglycemia, insulin and insulin delivery systems, the care of children with diabetes, and diabetes identification cards and care information. This is followed by sections that present tools and information for parents and school nurses. The section for parents focuses on general information about diabetes, the responsibilities of parents who have a child with diabetes, appropriate accommodations for a special needs child under the law, care planning, the age related responsibilities of children, psychosocial aspects of the child with diabetes, factors causing emotional distress for the child, sick day and travel guidelines, and medical identification products. The section for school nurses deals with care planning, training, staff training, appropriate accommodations for a special needs child under the law, sick day guidelines, and answers to questions about roles and responsibilities in relation to nursing procedures. Another section presents tools and information for teachers, administrators, school staff, and bus drivers. In addition, the manual includes an appendix that provides sample forms and letters and identifies numerous resources. 1 appendix. •
Living Well With Diabetes Source: Puyallup, WA: Good Samaritan Hospital. 1992. 63 p. Contact: Available from Good Samaritan Hospital. Diabetes Education Center, 407 14th Avenue SE, Puyallup, WA 98372. (206) 848-6661, ext. 1633. PRICE: $24.94 each, 10 or more $19.95 each; matching overheads $10 per set, plus $4.50 shipping and handling for over 5 manuals. Summary: This manual, intended for use in class instruction, is designed to help people newly-diagnosed with diabetes understand the disease and their role in diabetes management. Topics include a brief definition of diabetes, blood glucose testing, hypoglycemia, hyperglycemia, meal planning, exchange lists, sweeteners, fiber, fat and cholesterol, food labels, dining out, alcohol, cooking tips and cookbooks, exercise, insulin and oral hypoglycemic agents, long-term complications, care during illness (sick days), the psychosocial issues of living with diabetes, and support services. The topics are categorized into five class sessions and a 1-month follow-up meeting. Throughout the manual, charts and diagrams illustrate the material being presented.
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Manual for Management of Diabetes Mellitus: A Hong Kong Chinese Perspective Source: Hong Kong: Chinese University Press. 1998. 144 p. Contact: Available from Chinese University Press. Chinese University of Hong Kong, Sha Tin, N.T., Hong Kong. (852) 2609 6508. Fax (852) 2603 6692. E-mail: cup @cuhk.hk. PRICE: $19.00 plus shipping and handling. ISBN: 9622017576.
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Summary: This manual, which combines the latest international and Chinese information on diabetes, serves as a quick reference to all health care personnel involved in the management of diabetes. The manual begins with a chapter on the classification and pathogenesis of diabetes, focusing on intermediary metabolism, insulin, and counterregulatory hormones; the classification, presentation, and pathogenesis of diabetes; the overlap between type 1 and type 2 diabetes; and diabetes in Chinese people. This is followed by a chapter on the diagnosis of diabetes. Topics include the American Diabetes Association and World Health Organization diagnostic criteria and the oral glucose tolerance test. The third chapter recommends standards of medical care for patients who have diabetes, focusing on the initial visit, continuing care, the annual assessment, target values, hospital admission criteria, and referral for specialist assessment. The next chapter addresses the issue of patient education. Topics include health beliefs and affective responses, knowledge and skills, patient rights and roles, obstacles to glycemic control, self monitoring of blood glucose, insulin administration, sick day management, hypoglycemia, diabetic complications, treatment noncompliance, psychosociological problems, and finances. The fifth chapter focuses on the dietary management of diabetes and exercise in diabetes. Diet-related topics include the goals of dietary management, diet composition, healthy eating and dining out guidelines, food choices, weight control, and sweeteners. This is followed by a chapter on oral drugs for treating diabetes, including sulfonylureas, biguanides, antiabsorptive drugs, antiobesity drugs, and insulin and oral agent combinations. The next chapter discusses insulin use in terms of indications for use, actions and duration, types, regimen, dosage, adjustment of dosage, and use while travelling. The eighth chapter describes diabetic complications, including ophthalmic complications, diabetic foot, diabetic neuropathy, and microalbuminuria and renal involvement. This is followed by chapters on the treatment of hypertension and dyslipidemia. Perioperative management of people who have poorly and well controlled type 1 or type 2 diabetes is the topic of the next chapter. This is followed by a chapter on diabetic emergencies such as diabetic ketoacidosis, hyperosmolar nonketotic coma, and lactic acidosis. Remaining chapters discusses the diagnosis and management of gestational diabetes and the primary, secondary, and tertiary prevention of diabetes. 2 appendices. 9 figures. 1 table. •
Foods That Harm, Foods That Heal: An A-Z Guide to Safe and Healthy Eating Source: Pleasantville, NY: Reader's Digest. 1997. 400 p. Contact: Available from Customer Service, Reader's Digest. Pleasantville, NY 10570. (800) 846-2100. PRICE: $30.00. ISBN: 0895779129. Summary: This nutrition reference book features more than 400 photographs and illustrations with more than 400 A to Z entries on a vast range of foods and health concerns, including caffeine, cancer, diabetes, fast food, garlic, heart disease, influenza, osteoporosis, pregnancy, sexually transmitted diseases, and vegetarianism. The book is designed to help families understand the close links between foods and wellness. Each food entry provides at-a-glance information of its nutrients (or lack of) and its benefits and drawbacks. Each ailment is accompanied by a list of foods and beverages that are considered safe, and what foods or beverages should be cut down or avoided altogether. Case studies help to illustrate various topics. There are special features on eating during different life stages, from infancy to old age, as well as such issues as genetically altered foods, irradiation, pesticides, and pollution. Other topics include how to cook foods to achieve maximum nutritional benefits; which dietary supplements really work; tips on exercise, food storage, and reading food labels; an instructive analysis of the most popular diet regimes; and controversial foods and additives such as eggs, nitrites, bran,
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cheese, milk, fat, wine, and alcohol. A glossary defines unfamiliar or technical terms; there is also a listing of organizations that can provide further information and resources. Topics specifically related to diabetes include atherosclerosis, basic food groups, blood pressure, carbohydrates, childhood and adolescent nutrition, cholesterol, convenience and fast foods, cravings, diabetes, dieting and weight control, exercise and diet to boost energy and lift mood, eye disorders, fats, fiber, heart disease, hypoglycemia, immune system, impotence, indigestion and heartburn, infertility, juicing, kidney diseases, malnutrition and dietary deficiencies, medicine-food interactions, menopause, minerals, neuralgia, obesity, organic foods, osteoporosis, pregnancy, preparation and storage of food, protein, restaurants and eating out, salt and sodium, sleep and diet, smoking and diet, sports nutrition, stress, stroke, sugar and other sweeteners, supplements, traveler's health, vegetarian diets, and vitamins. •
Putting Your Diabetes on the Pump Source: Alexandria, VA: American Diabetes Association. 2001. 59 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: $7.95 plus shipping and handling. ISBN: 1580401414. Summary: This pocket sized handbook familiarizes readers with how people with diabetes can use an insulin pump to keep blood glucose (sugar) levels within target ranges. The author notes that by using an insulin pump, the patient can match their insulin needs to their lifestyle, rather than take an insulin injection and match their activities to how the insulin is working. Pumps deliver rapid or short-acting insulin 24 hours a day through a catheter placed under the skin. Insulin doses are separated into basal rates, bolus doses to cover the carbohydrate in meals, and correction or supplemental doses. Basal insulin is delivered continuously over 24 hours and keeps the blood glucose levels in range between meals and at night. When the pump user eats, he or she uses buttons on the pump to give additional insulin called a bolus. The booklet describes the positive and negatives aspects of using an insulin pump, what to know before using the pump, good habits, the practicalities of wearing an insulin pump, infusion sets, equipment and supplies, blood glucose targets, exercise and sports, days off the pump, dealing with hyperglycemia (high levels of blood glucose) and hypoglycemia (low levels of blood glucose), coping with sick days, and skin care. The booklet concludes with some suggestions from others who already use the insulin pump for part of their diabetes management, a blank form for recordkeeping, and basic information about the American Diabetes Association. The booklet is illustrated with simple line drawings. 1 figure. 4 tables.
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Selected Diabetes and Nutrition Education Resources: For the Diabetes Professional Source: Chicago, IL: American Dietetic Association (ADA). 1999. 83 p. Contact: Available from American Dietetic Association. P.O. Box 97215, Chicago, IL 60678-7215. (800) 877-1600 ext. 5000. Fax (312) 899-4899. Website: www.eatright.org. PRICE: $12.00 for members; $14.50 for nonmembers. Summary: This publication is a directory of selected diabetes and nutrition education resources for the diabetes professional to use in teaching people who have diabetes and their families. Print and audiovisual resources are included for various subject areas related to diabetes nutrition management and other aspects of diabetes care. Specifically, resource topics include comprehensive diabetes information, fundamental
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diabetes self management skills, general facts about diabetes, blood and urine self monitoring techniques, the management of blood glucose levels during an illness, foot care techniques, the action and use of oral agents and insulin, hypoglycemia, meal planning, advanced diabetes self management skills, intensive insulin therapy and pump therapy regimens, food exchange lists, carbohydrate counting, gestational diabetes, physical activity, complications, weight loss or maintenance, psychosocial concerns, comprehensive education programs, and diabetes prevention. Other resources include various types of cookbooks; material written for children, adolescents, men, women, and parents; magazines and newsletters; and diabetes-related agencies and associations. Each resource is listed alphabetically by title in each subject category. Resource entries may include the author or publisher, copyright date, ISBN number, address or telephone number for ordering, cost, number of pages, format, and a summary. In addition, each entry includes symbols that designate the target audience age, group or type of diabetes, educational use, and reading level for which the resource is appropriate. An index is also included. 3 appendices. •
Management of Diabetes Mellitus. 2nd ed Source: Durant, OK: Essential Medical Information Systems, Inc. 1991. 267 p. Contact: Available from Essential Medical Information Systems, Inc. P.O. Box 1607 Durant, OK 74702. (800) 225-0694. FAX (405) 924-9414. PRICE: $12.95 plus $1.95 shipping and handling. Bulk prices available. ISBN: 0929240316. Summary: This reference guide for the management of diabetes mellitus consists of 34 chapters on the following topics: fuel-hormonal dynamics; the cellular effects of insulin; diagnosis; insulin-dependent diabetes mellitus; noninsulin-dependent diabetes mellitus; secondary causes; effects of glucose normalization; laboratory methods; self blood glucose monitoring; diet therapy; methods of exercise; oral agents; insulin; dealing with the difficult patient; hypoglycemia; diabetic ketoacidosis; hyperglycemic hyperosmolar nonketotic coma; diabetes and the eyes; nephropathy; hypertension; neuropathy; sexuality; foot disease; lipids; macrovascular disease; digestive disease; prepartum planning and genetic counseling; glucose control during pregnancy; obstetrical considerations; surgery; outpatient sick day therapy; pump therapy; pancreatic transplantation; and enhancing adherence. Most chapters include references, charts, and figures where necessary.
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Diabetes Ready-Reference Guide for Health Care Professionals Source: Alexandria, VA: American Diabetes Association. 2000. 56 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: $29.95 plus shipping and handling. ISBN: 1580400116. Summary: This reference guide provides health professionals with clear, concise guidelines for effective direct or indirect care of patients who have diabetes. The guide is tabbed for quick access to the various topics. Sections focus on the causes, characteristics, and treatment of type 1, type 2, and gestational diabetes; the diagnosis of diabetes; monitoring blood glucose through the use of self monitoring and the glycated hemoglobin and fructosamine test; the dietary management of diabetes and the meal planning approaches for obtaining optimal glucose and weight management; and the benefits of exercise and ways to start an exercise program. Other sections deal with the dosage, duration of action, and side effects of oral agent medications; types of insulin
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and the dosing and administration of insulin; the effects of nonprescription and prescription medications on diabetes control; acute complications such as hypoglycemia, diabetic ketoacidosis, and hyperglycemic hyperosmolar nonketotic syndrome; chronic complications such as cardiovascular disease, diabetic retinopathy, diabetic retinopathy, diabetic nephropathy, diabetic neuropathy, and autonomic dysfunction; foot care; sick day rules; and travel guidelines. The guide also includes a glossary and a bibliography. •
Serving Individuals with Diabetes who are Blind or Visually Impaired: A Resource Guide for Vocational Rehabilitation Counselors Source: Mississippi State, MS: Rehabilitation Research and Training Center on Blindness and Low Vision, Mississippi State University. 1997. 227 p. Contact: Available from Rehabilitation Research and Training Center on Blindness and Low Vision, Mississippi State University. Publications Manager, P.O. Drawer 6189, Mississippi State, MS 39762. (601) 325-2001 or (601) 325-8693. Fax (601) 325-8989. TDD (601) 325-8693. PRICE: $25.00 in any format. Summary: This resource guide is designed to help counselors better serve individuals with diabetes who are blind or visually impaired. The guide refers readers to a large collection of resources on various diabetes publications, medications, and appliances. Five sections cover an introduction to diabetes; self management; current medical issues; employment issues; and emotional aspects of diabetes. Topics include myths about diabetes; diabetic eye disease; new nutrition guidelines for diabetes management; oral diabetes medications; diabetes and medications; insulin and measurement devices and systems; maintaining the proper temperature of insulin; blood glucose control; 'talking' blood glucose monitoring systems; and noninvasive glucose monitors. The authors also discuss diabetes and the feet; kidney failure, dialysis, and transplantation; pancreas transplantation; arthritis and diabetes; diabetes and yeast infections; hypoglycemia; diabetic peripheral neuropathy; diabetes and men's sexual health; cardiovascular health; diabetic ketoacidosis; diabetic dermopathy; diabetes and the Individualized Written Rehabilitation Program (IWRP); the use of Braille; health insurance; and scleral shells. The book's appendix includes lists of diabetes-related organizations, publications, listservs, and World Wide Web sites; sources of low-sugar products and products for the blind; and diabetes equipment and supplies, including insulin syringe magnifiers. The resource guide is available in large print, Braille, audiocassette, and computer diskette.
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American Diabetes Association Complete Guide to Diabetes: The Ultimate Home Diabetes Reference. 2nd ed Source: Alexandria, VA: American Diabetes Association. 1999. 514 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: $23.95 plus shipping and handling. ISBN: 1580400388. Summary: This sourcebook provides people who have diabetes with expert advice, written in clear, easy to understand language, on every aspect of type 1, type 2, and gestational diabetes. The book begins with a chapter that provides an overview of type 1, type 2, and gestational diabetes. This is followed by a chapter that offers guidelines for designing a diabetes plan and describes options for treating diabetes, including insulin therapy, pancreas and islet transplantation, diet therapy, and oral diabetes medications. The third chapter provides suggestions for selecting a diabetes care team
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and answers questions about the glycated hemoglobin test. The next chapter describes types of insulin; explains how to buy, store, and administer insulin; and discusses various insulin plans. This is followed by a chapter that focuses on achieving glucose control. Topics include the impact of food, insulin, exercise, stress, and illness on blood glucose; self monitoring of blood glucose; and the causes and treatment of hypoglycemia and hyperglycemia. Chapter six provides information on diabetes tools, including blood glucose meters, test strips, lancets, and miscellaneous supplies. The focus of chapter seven is on intensive diabetes management. Topics include standard diabetes control versus tight control, goals for type 1 and type 2 diabetes, and intensive management techniques. Chapter eight discusses healthy eating in terms of creating a healthy meal plan using the food pyramid and using medical nutrition therapy. The next chapter offers suggestions for beginning an exercise program, exercising safely, and finding a desirable exercise. Other topics include the impact of exercise on blood glucose levels and exercise during pregnancy. Chapter 10 examines diabetes complications and their prevention and treatment. Complications include cardiovascular disease, diabetic retinopathy, diabetic nephropathy, diabetic neuropathy, and infections. Other chapters discuss the impact of diabetes on sexual health and pregnancy, the psychological impact of diabetes, and the effect of diabetes on other family members. Remaining chapters examine diabetes in the workplace, in the military, and at school and offer advice for working with the health care system. The book includes a glossary, an index, and lists of resources and helpful websites. 1 appendix. 9 figures. •
Rufus Comes HoMen Source: Plainview, NY: JayJo Books. 1998. 34 p. Contact: Available from JayJo Books. 135 Dupont Street, P.O. Box 760, Plainview, NY 11803-0760. (800) 999-6884. Fax (800) 262-1886. E-mail:
[email protected]. Website: www.JayJo.com. PRICE: $11.95 plus shipping and handling. Order number: BK190H170024. ISBN: 891383027. Summary: This story book was written for children who have recently been diagnosed with type 1 diabetes. The book follows the story of a young boy, Brian, and his parents, as they go through the process of diabetes diagnosis and learning how to manage the disease. Topics include the symptoms of diabetes, testing for blood glucose, complications of diabetes, the physiology of insulin and blood glucose levels, the use of insulin injections, the role of meal planning and nutrition, hyperglycemia (high blood glucose levels) and hypoglycemia (low blood glucose levels), and the emotions of being diagnosed with diabetes. The story tells the tale of a stuffed bear, Rufus, being used to help the child with diabetes not feel so alone; the bear has diabetes too, and special patches where blood glucose testing and insulin shots could be pretended. The book ends with information telling readers how they can purchase a Rufus bear. The book is filled with colorful illustrations.
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Endocrinology. 4th ed Source: Philadelphia, PA: Harcourt Health Sciences. 2001. 3 v., 3048 p. Contact: Available from W.B. Saunders. 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-2452 or (314) 453-7010. Fax (800) 568-5136 or (314) 453-7095. E-mail:
[email protected]. Website: customerservice.wbsaunders.com. PRICE: $495.00 plus shipping and handling. ISBN: 0721678408 (three volume set). Summary: This three volume set of books provides a complete, authoritative, up to date analysis of endocrine disease and basic endocrine physiology. This edition consists of
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194 chapters that cover every aspect of endocrinology in detail by an authority in the field. About one third of the chapters are new, and the remainder have been rewritten and updated. Topics covered in volume one include the principles of hormone action; neuroendocrinology and the pituitary gland; growth and maturation; immunology and endocrinology; obesity, anorexia nervosa, and nutrition in endocrinology; and diabetes mellitus, carbohydrate metabolism, and lipid disorders. Chapters on diabetes mellitus focus on anatomy and physiology, classification, etiology, diagnosis, and treatment. Specific clinical disorders discussed include syndromes of insulin resistance, oculopathy, neuropathy, nephropathy, diabetic foot complications, ketoacidosis, hyperosmolar coma, lactic acidosis, hypoglycemia, atherosclerosis, syndrome X, and hyperglycemia. Volume two includes information on the parathyroid gland, calciotropic hormones, bone metabolism, the thyroid gland, the adrenal gland, and glucocorticoids. Topics covered in volume three include endocrine hypertension and mineralocorticoids, reproductive endocrinology and sexual development, female reproduction, endocrinology of the breast, male reproduction, endocrinology and pregnancy, endocrine tumor syndromes, and endocrine testing and treatment. Numerous figures. Numerous tables. Numerous references. •
Encyclopedia of Alcoholism. 2nd ed Source: New York, NY: Facts on File, Inc. 1991. 346 p. Contact: Available from Facts on File, Inc. 460 Park Avenue South, New York, NY 10016. (212) 683-2244. PRICE: $45. Shipping and handling free if prepaid. ISBN: 081601955X. Summary: This volume presents a dictionary approach to information about alcoholism. With more than 600 entries, the encyclopedia defines and explains all facets of alcoholism: biological, medical and psychological areas, its social and economic impact, legal implications, terminology used in the treatment of the disease, slang, organizations that deal with alcoholism, various theories on the causes of the disease, and the prevalence of alcohol abuse around the world and what different countries have tried to do about controlling it. Entries of interest to those in the field of digestive diseases include those about alcoholic hepatitis, alcoholic liver disease, alcoholic myopathy, black Americans, blood sugar, cirrhosis, diabetes, diseases, gastrointestinal tract, hemochromatosis, hypoglycemia, intestine, liver, Mallory-Weiss syndrome, nutrition, pancreas, post-necrotic cirrhosis, stomach, and Switzerland. Appendices include tables and figures and sources of information. A subject index is included. 620 references.
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Managing Your Diabetes: A Comprehensive Study Guide for Patients and Their Health Care Professionals Source: Indianapolis, IN: Eli Lilly and Company. 1994. 107 p. Contact: Available from Eli Lilly and Company. Lilly Corporate Center, Indianapolis, IN 46285. (800) 545-5979 or (317) 276-2000. PRICE: Single copy free. Summary: This workbook provides an overview of diabetes and information on ways to control it. Designed primarily for people newly diagnosed, the workbook has 14 chapters. Topics include a definition of diabetes, its symptoms, and causes; the importance of the team approach to diabetes care; meal planning; exercise; insulin; oral hypoglycemic agents; blood glucose testing; ketone testing; pattern management; hypoglycemia; hyperglycemia; ketoacidosis; long-term complications; and general health care tips, including skin and foot care, sick days, and travel. Many of these sections have blanks to be filled in with the help of a doctor, nurse, pharmacist, or diabetes educator. Full-color photographs and colorful charts illustrate the material
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presented. The book concludes with a glossary of terms. The booklet is also available in Chinese, Spanish, Turkish, and Italian. •
Handbook of Diagnostic Endocrinology Source: Totowa, NJ: The Humana Press, Inc. 2003. 360 p. Contact: Humana Press, Inc. 999 Riverview Dr., Suite 208 Totowa, NJ 07512. (973) 2561699. Fax (973) 256-8341. E-mail:
[email protected] PRICE: $99.50 plus shipping and handling. ISBN: 0896037576. Summary: With the rapid development of new and more reliable diagnostic tests, and aided by the molecular and genetic approaches that continue to deepen the understanding of these diseases, the ability to diagnose patients with endocrine disease has dramatically increased. In this book, physicians concisely explain the pathophysiology and clinical manifestations of these disorders and survey all the latest laboratory tests used in their diagnosis. Topics range widely from an overview of the diagnosis of diabetes and the long-term monitoring of its complications to the evaluation of menstrual dysfunction. Other topics include the diagnosis of pituitary tumors, Cushing's syndrome, thyroid disease, and hypoglycemia; the evaluation of endocrine-induced hypertension; the assessment of dyslipidemia and obesity; new approaches to diagnosing hypercalcemia and hypocalcemia, osteoporosis, hypogonadism and erectile dysfunction, and hyperandrogenism in women. The authors review the complex physiological basis of the relevant endocrine processes and provide recommendations for the follow up and long term management of patients. Each chapter concludes with references and the text concludes with a subject index.
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Strength and Compassion in Kidney Failure Source: Norwell, MA: Kluwer Academic Publishers. 1998. 221 p. Contact: Available from American Association of Kidney Patients (AAKP). 100 South Ashley Drive, Suite 280, Tampa, FL 33602. (800) 749-2257 or (813) 223-7099. Fax (813) 223-0001. E-mail:
[email protected]. PRICE: $25.00 plus shipping and handling. ISBN: 079235236X. Summary: Written to celebrate life rather than lament chronic illness, this book offers a collection of medical columns, short stories, and letters that recount an upbeat tale of coping, surviving, and prevailing. The author, a medical technician, wife, and mother, faced progressive loss of sight and ambulation due to kidney failure, diabetes, and Addison's disease. The author includes hints for managing the necessities of diet therapy, handling time changes during travel, and adjusting insulin treatment to adapt to different levels of activity. Other topics covered include drug therapy, medical ethics, holidays, family interactions and relationships, depression and other emotions, skin problems, the physical side of diabetes, coping with constant adaptation to changes in one's body, the Diabetes Control and Complications Trial (DCCT), systemic joint and bone disease in diabetes, insulin therapy, hyperglycemia and hypoglycemia, hemodialysis, end stage renal disease, and kidney transplantation. Each item is briefly introduced by the editor, who is the author's husband. The author died in 1997 at the age of 61 of complications of type 1 diabetes.
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Book Summaries: Online Booksellers Commercial Internet-based booksellers, such as Amazon.com and Barnes&Noble.com, offer summaries which have been supplied by each title’s publisher. Some summaries also include customer reviews. Your local bookseller may have access to in-house and commercial databases that index all published books (e.g. Books in Print®). IMPORTANT NOTE: Online booksellers typically produce search results for medical and non-medical books. When searching for “hypoglycemia” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “hypoglycemia” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “hypoglycemia” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •
A Natural Approach: Diabetes and Hypoglycemia Action Series by Michio Kushi, John D. Mann (Editor); ISBN: 0870406159; http://www.amazon.com/exec/obidos/ASIN/0870406159/icongroupinterna
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A taste for life : recipes for a high protein diet : especially suited for hypoglycemia, diabetes, and weight reduction by Marcia Grad; ISBN: 068414381X; http://www.amazon.com/exec/obidos/ASIN/068414381X/icongroupinterna
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Alcoholism, stress, hypoglycemia, with diets by C. Jean Poulos; ISBN: 089368600X; http://www.amazon.com/exec/obidos/ASIN/089368600X/icongroupinterna
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Carlton Fredericks' New Low Blood Sugar and You by Carlton Fredericks (1985); ISBN: 0399510877; http://www.amazon.com/exec/obidos/ASIN/0399510877/icongroupinterna
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Cooking for Health: Diabetes and Hypoglycemia (MacRobiotic Food and Cooking Series) by Aveline Kushi, et al; ISBN: 0870406175; http://www.amazon.com/exec/obidos/ASIN/0870406175/icongroupinterna
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Current Views on Hypoglycemia and Glucagon: Proceedings (Serono Symposia: No 30) by Italy)/ Andreani, Dominico European Symposium on Hypoglycemia 1979 Rome (Editor), Dominico Andreani (Editor); ISBN: 0120586800; http://www.amazon.com/exec/obidos/ASIN/0120586800/icongroupinterna
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Diabetes & Hypoglycemia: Your Natural Guide to Healing with Diet, Vitamins, Minerals, Herbs, Exercise, and Other Natural Methods by Michael T., N.D. Murray; ISBN: 1559584262; http://www.amazon.com/exec/obidos/ASIN/1559584262/icongroupinterna
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Do's and Don'ts of Hypoglycemia: An Everday Guide to Low Blood Sugar by Roberta Ruggiero (2003); ISBN: 088391087X; http://www.amazon.com/exec/obidos/ASIN/088391087X/icongroupinterna
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Dr Donsbach Tells You What You Always Wanted to Know About Hypoglycemia & Diabetes (Dr. Donsbach Tell You What You Always Wanted to Know About) by Kurt W. Konsbach; ISBN: 156959564X; http://www.amazon.com/exec/obidos/ASIN/156959564X/icongroupinterna
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Effects of Stress and Hypoglycemia in Handwriting by Patricia Wellingham-Jones; ISBN: 0939221020; http://www.amazon.com/exec/obidos/ASIN/0939221020/icongroupinterna
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Endocrine and Metabolic Disorders Sourcebook: Basic Information for the Layperson About Pancreatic and Insulin-Related Disorders Such As Pancreatis, Diabetes, and
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Hypoglycemia (Health Reference Series, Vol 36) by Linda M. Shin (Editor), Linda M. Ross (Editor) (1998); ISBN: 0780802071; http://www.amazon.com/exec/obidos/ASIN/0780802071/icongroupinterna •
Hope for Hypoglycemia by Broda Barnes; ISBN: 0686298616; http://www.amazon.com/exec/obidos/ASIN/0686298616/icongroupinterna
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How to Live With Hypoglycemia by Charles Weller; ISBN: 0385083467; http://www.amazon.com/exec/obidos/ASIN/0385083467/icongroupinterna
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Hypoglycemia by Health Education (Editor) (1988); ISBN: 0937721107; http://www.amazon.com/exec/obidos/ASIN/0937721107/icongroupinterna
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Hypoglycemia by Marilyn Light, et al; ISBN: 0879833025; http://www.amazon.com/exec/obidos/ASIN/0879833025/icongroupinterna
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Hypoglycemia by Paavo Airola; ISBN: 0685539458; http://www.amazon.com/exec/obidos/ASIN/0685539458/icongroupinterna
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Hypoglycemia by Jeraldine Saunders; ISBN: 0523422407; http://www.amazon.com/exec/obidos/ASIN/0523422407/icongroupinterna
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Hypoglycemia (Menus for Better Health) by Joyce Sorenson, Nancy Murray; ISBN: 0911638148; http://www.amazon.com/exec/obidos/ASIN/0911638148/icongroupinterna
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Hypoglycemia (Serono Symposia Publications, Vol 38) by D. Andreani (Editor), et al (1987); ISBN: 0881673218; http://www.amazon.com/exec/obidos/ASIN/0881673218/icongroupinterna
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Hypoglycemia (SuDoc HE 20.3323/2:H 99) by U.S. Dept of Health and Human Services; ISBN: B00010RLM4; http://www.amazon.com/exec/obidos/ASIN/B00010RLM4/icongroupinterna
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Hypoglycemia : proceedings of the Europ. Symposium, Rome; ISBN: 3135323013; http://www.amazon.com/exec/obidos/ASIN/3135323013/icongroupinterna
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Hypoglycemia : the deadly roller coaster by David G. Williams; ISBN: 0944649025; http://www.amazon.com/exec/obidos/ASIN/0944649025/icongroupinterna
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Hypoglycemia and Diabetes Wellness Guide by Freda Whalen, et al; ISBN: 0963820117; http://www.amazon.com/exec/obidos/ASIN/0963820117/icongroupinterna
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Hypoglycemia and the Need to Practice It by Joel Zizik (1994); ISBN: 0932616429; http://www.amazon.com/exec/obidos/ASIN/0932616429/icongroupinterna
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Hypoglycemia Control Cookery by Dorothy Revell; ISBN: 0425057348; http://www.amazon.com/exec/obidos/ASIN/0425057348/icongroupinterna
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Hypoglycemia Fact or Fad: What You Should Know About Low Blood Sugar by L. Bennion; ISBN: 9997801636; http://www.amazon.com/exec/obidos/ASIN/9997801636/icongroupinterna
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Hypoglycemia For Dummies(r) by Cheryl Chow (Author), et al; ISBN: 0764554905; http://www.amazon.com/exec/obidos/ASIN/0764554905/icongroupinterna
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Hypoglycemia in childhood : evaluation of diagnostic procedures by Klaus A. Zuppinger; ISBN: 3805520611; http://www.amazon.com/exec/obidos/ASIN/3805520611/icongroupinterna
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Hypoglycemia in Clinical Diabetes by Brian M. Frier (Editor), Barrie M. Fisher (Editor) (2000); ISBN: 0471982644; http://www.amazon.com/exec/obidos/ASIN/0471982644/icongroupinterna
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Hypoglycemia in Infancy and Childhood (Current Reviews in Pediatrics) by Albert Aynsley-Green (1985); ISBN: 0443031843; http://www.amazon.com/exec/obidos/ASIN/0443031843/icongroupinterna
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Hypoglycemia in the Newborn by Helen L. Dulock; ISBN: 0865250499; http://www.amazon.com/exec/obidos/ASIN/0865250499/icongroupinterna
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Hypoglycemia Syndromes by T.S Danowski; ISBN: 0683023462; http://www.amazon.com/exec/obidos/ASIN/0683023462/icongroupinterna
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Hypoglycemia: A Better Approach by Paavo Airola (1984); ISBN: 093209001X; http://www.amazon.com/exec/obidos/ASIN/093209001X/icongroupinterna
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Hypoglycemia: A Nutritional Approach (Todays Health Series, No 9) by Louise Tenney, Rita Elkins (1997); ISBN: 091392377X; http://www.amazon.com/exec/obidos/ASIN/091392377X/icongroupinterna
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Hypoglycemia: Directory of Authors of New Medical and Scientific Reviews With Subject Index (1995); ISBN: 0788306030; http://www.amazon.com/exec/obidos/ASIN/0788306030/icongroupinterna
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Hypoglycemia: Fact or Fad?: What You Should Know About Low Blood Sugar by Lynn J. Bennion; ISBN: 0517550741; http://www.amazon.com/exec/obidos/ASIN/0517550741/icongroupinterna
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Hypoglycemia: Pathophysiology, Diagnosis, and Treatment by Philip E. Cryer; ISBN: 019511325X; http://www.amazon.com/exec/obidos/ASIN/019511325X/icongroupinterna
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Hypoglycemia: The Classic Healthcare Handbook Completely by Jeraldine Saunders, Harvey M. Ross (2002); ISBN: 075820132X; http://www.amazon.com/exec/obidos/ASIN/075820132X/icongroupinterna
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Hypoglycemic Disorders: Pathogenesis, Diagnosis and Treatment by F. John Service; ISBN: 0816122105; http://www.amazon.com/exec/obidos/ASIN/0816122105/icongroupinterna
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Low Blood Sugar : The Hidden Menace of Hypoglycemia by Clement G. Martin (Author); ISBN: 0671764101; http://www.amazon.com/exec/obidos/ASIN/0671764101/icongroupinterna
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LOW BLOOD SUGAR Hypoglycemia: The 20th Century Epidemic? by Martin Budd (1983); ISBN: 0806977922; http://www.amazon.com/exec/obidos/ASIN/0806977922/icongroupinterna
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Low Blood Sugar-(Hypoglycemia) by Carlton Fredricks, Carlton Fredericks; ISBN: 0441497632; http://www.amazon.com/exec/obidos/ASIN/0441497632/icongroupinterna
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Low blood sugar; a doctor's guide to its effective control by J. Frank Hurdle; ISBN: 013541086X; http://www.amazon.com/exec/obidos/ASIN/013541086X/icongroupinterna
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Medical Approach Versus the Nutritional Approach to Hypoglycemia by Salem Kirban; ISBN: 0912582561; http://www.amazon.com/exec/obidos/ASIN/0912582561/icongroupinterna
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Nutrigenetics: New Concepts for Relieving Hypoglycemia by R.O. Brennan; ISBN: 0871311879; http://www.amazon.com/exec/obidos/ASIN/0871311879/icongroupinterna
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Preventing Reactive Hypoglycemia: The Great Medical Dilemma by Fred D. Hofeldt (1983); ISBN: 0875272142; http://www.amazon.com/exec/obidos/ASIN/0875272142/icongroupinterna
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Recent Advances on Hypoglycemia (Serono Symposia Publications from Raven Pr, Vol. 89) by D. Andreani, et al; ISBN: 0881679038; http://www.amazon.com/exec/obidos/ASIN/0881679038/icongroupinterna
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The 2002 Official Patient's Sourcebook on Hypoglycemia: A Revised and Updated Directory for the Internet Age by Icon Health Publications (2002); ISBN: 059783301X; http://www.amazon.com/exec/obidos/ASIN/059783301X/icongroupinterna
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The Do's and Don't s of Low Blood Sugar: An Everyday Guide to Hypoglycemia by Roberta Ruggiero; ISBN: 0811907910; http://www.amazon.com/exec/obidos/ASIN/0811907910/icongroupinterna
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The Hypoglycemia-Diabetes Cope Book: A Guide to Healthy Living by Freda Whalen (1993); ISBN: 0963820109; http://www.amazon.com/exec/obidos/ASIN/0963820109/icongroupinterna
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The Low Blood Sugar Cookbook; ISBN: 0553238353; http://www.amazon.com/exec/obidos/ASIN/0553238353/icongroupinterna
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The Low Blood Sugar Cookbook. by Francyne. Davis; ISBN: 0448015765; http://www.amazon.com/exec/obidos/ASIN/0448015765/icongroupinterna
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The Low Blood Sugar Cookbook: Sugarless Cooking for Everyone by Edward A. Krimmel, Patricia T. Krimmel (1992); ISBN: 0916503011; http://www.amazon.com/exec/obidos/ASIN/0916503011/icongroupinterna
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The Low Blood Sugar Gourmet Cookbook, by Sylvia G. L., Dannett; ISBN: 0847313484; http://www.amazon.com/exec/obidos/ASIN/0847313484/icongroupinterna
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The Low Blood Sugar Handbook: You Don't Have to Suffer. by Edward A. Krimmel, et al (1992); ISBN: 0916503046; http://www.amazon.com/exec/obidos/ASIN/0916503046/icongroupinterna
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The Psychometabolic Blues: Practical Solutions to Anxiety, Depression, Hypoglycemia, and Other Stressful Problems by Jerome Marmorstein; ISBN: 0912800585; http://www.amazon.com/exec/obidos/ASIN/0912800585/icongroupinterna
The National Library of Medicine Book Index The National Library of Medicine at the National Institutes of Health has a massive database of books published on healthcare and biomedicine. Go to the following Internet site, http://locatorplus.gov/, and then select “Search LOCATORplus.” Once you are in the search area, simply type “hypoglycemia” (or synonyms) into the search box, and select “books only.” From there, results can be sorted by publication date, author, or relevance. The following was recently catalogued by the National Library of Medicine:11 11 In addition to LOCATORPlus, in collaboration with authors and publishers, the National Center for Biotechnology Information (NCBI) is currently adapting biomedical books for the Web. The books may be accessed
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A study of hypoglycemia in leukemic mice. Author: Silverstein, Murray N.,; Year: 1958; [Minneapolis] 1963
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Alimentary hypoglycemia after stomach operations and influence of gastric emptying on glucose tolerance curve. Author: Evensen, Ole K.; Year: 1968; Oslo, Grøndahl, 1942
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Diabetes, with a chapter on hypoglycemia, by 54 authors. Author: Williams, Robert Hardin.; Year: 1966; [New York] Hoeber [c1960]
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Endocrinologic approach to the etiology and treatment of functional hypoglycemia; or, Physicians guideline to diagnosis and treatment of hypoglycemia or the hypoadrenocortical state. Covers non-surgical treatment of all hypoglycemia states including those of alcoholism and drug addiction. Author: Hypoglycemia Foundation.; Year: 1969; [Scarsdale, N. Y., c1966]
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How to live with hypoglycemia, by Charles Weller and Brian Richard Boylan. Author: Weller, Charles,; Year: 1970; Garden City, N. Y., Doubleday, 1968
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Hypoglycemia: your bondage or freedom? Author: Barmakian, Richard,; Year: 1958; Irvine, Calif.: Altura Health Publishers, c1976
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Hypoglycemia [by] Gerald T. Perkoff [and] Frank H. Tyler. Author: Perkoff, Gerald Thomas,; Year: 1972; Chicago, Year Book Publishers, 1959
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Hypoglycemia and the hypoglycemic syndrome, by A. J. Kauver and Martin G. Goldner. Author: Kauvar, Abraham Judah,; Year: 1974; Springfield, Ill., Thomas [1954]
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Hypoglycemia: pathogenesis, diagnosis, and treatment. Author: Kogut, Maurice D.,; Year: 1942; Chicago, Year Book Medical Publishers, 1974; ISBN: 0815199058 http://www.amazon.com/exec/obidos/ASIN/0815199058/icongroupinterna
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Low blood sugar and you, by Carlton Fredericks and Herman Goodman. Author: Fredericks, Carlton.; Year: 1959; New York, Constellation International [c1969]
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Low blood sugar. Author: Steincrohn, Peter J. (Peter Joseph),; Year: 1972; Chicago, Regnery [c1972]
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Low blood sugar; a doctor's guide to its effective control. Author: Hurdle, J. Frank (John Frank),; Year: 1966; West Nyack, N. Y., Parker [c1969]; ISBN: 13541086X
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Potassium concentration in human gastric juice, with special reference to parasympathetic stimulation during insulin hypoglycemia; a clinical study. Author: Saemundsson, Jóhann,; Year: 1968; Copenhagen. E. Munksgaard, 1948
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Reactions to hypoglycemia in insulin-dependent diabetics, with special reference to adrenergic effects Author: Lager, Ibe.; Year: 1973; Göteborg: [s.n.], 1981
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The effect of hypoglycemia on various physiological parameters in the brain of cats Author: Cilluffo, John Mariano.; Year: 1973; [Minneapolis?: s.n.], 1982
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The hypoglycemia syndromes Author: Danowski, T. S. (Thaddeus Stanley),; Year: 1960; Pittsburgh: Harper Printing Service, 1978
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The low blood sugar cookbook [by] Margo Blevin and Geri Ginder. Author: Blevin, Margo.; Year: 1954; Garden City, N. Y., Doubleday [c1973]; ISBN: 0385051743 http://www.amazon.com/exec/obidos/ASIN/0385051743/icongroupinterna
in two ways: (1) by searching directly using any search term or phrase (in the same way as the bibliographic database PubMed), or (2) by following the links to PubMed abstracts. Each PubMed abstract has a "Books" button that displays a facsimile of the abstract in which some phrases are hypertext links. These phrases are also found in the books available at NCBI. Click on hyperlinked results in the list of books in which the phrase is found. Currently, the majority of the links are between the books and PubMed. In the future, more links will be created between the books and other types of information, such as gene and protein sequences and macromolecular structures. See http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Books.
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The low blood sugar gourmet cookbook, by Sylvia G. L. Dannett with Maureen McCabe. Author: Dannett, Sylvia G. L.,; Year: 1948; New York, Drake [c1974]; ISBN: 0877495998 http://www.amazon.com/exec/obidos/ASIN/0877495998/icongroupinterna
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Treatment of neuromuscular disorders; guest editor: Frank M. Howard, Jr. Treatment of hypoglycemia; guest editor: Buris R. Boshell. Author: Howard, Frank Melvin,; Year: 1968; [New York] Heober [c1966]
Chapters on Hypoglycemia In order to find chapters that specifically relate to hypoglycemia, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and hypoglycemia 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 “hypoglycemia” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on hypoglycemia: •
Sex, Pregnancy, and Hypoglycemia Source: in Lincoln, T.A.; Eaddy, J.A. Beating the Blood Sugar Blues. Alexandria, VA: American Diabetes Association. 2001. p.86-90. 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: $12.95 plus shipping and handling. ISBN: 1580400485. Summary: Diabetes can have an effect on a person's sexual health, both in their ability to physically enjoy sexual relations and in feeling like enjoying it. Good glucose control prevents the nerve and circulation damage that can interfere with a man's ability to have an erection and a woman's ability to have an orgasm. Good glucose control also can improve one's health and emotional state. This chapter on sex, pregnancy, and hypoglycemia (low blood glucose levels) is from a book that offers first hand knowledge from two doctors who have more than 100 years of combined experienced with the dayto-day balancing act of blood glucose (sugar) and diabetes. The authors, both of whom have type 1 diabetes, share their own stories as well as those of over 40 of their patients. In this chapter, the authors discuss the physiology of health sexuality, the impact of sexual activity on blood glucose levels (which is similar to other physical activities), the reluctance of patients to discuss sexuality with their physicians, the importance of preventing hypoglycemia during pregnancy (even before conception), the role of selfmonitoring of blood glucose (SMBG) during pregnancy, post childbirth considerations for mothers with diabetes, and the importance of careful planning, before and after the baby is born. 1 table.
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Reactive Hypoglycemia Source: in American Dietetic Association. Manual of Clinical Dietetics, Sixth Edition. Chicago, IL: American Dietetic Association. 2000. p. 337-340.
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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: 0880911875. Summary: Medical nutrition therapy (MNT) can be used to prevent symptoms of hypoglycemia (low blood glucose levels) after food ingestion in patients sensitive to carbohydrates (reactive hypoglycemia). This chapter on reactive hypoglycemia is from a comprehensive manual of clinical dietetics designed to help dietitians, physicians, and nurses deliver quality nutrition care. The chapter includes the purpose of nutrition care, the indications for use, a description of the diet, meal planning approaches, a definition of the disease or condition, and a discussion section. The authors describe the differences between fasting and postprandial (after a meal, also called reactive) hypoglycemia. 14 references. •
Prevention and Correction of Hypoglycemia Source: in Sperling, M.A. Type I Diabetes: Etiology and Treatment. Totowa, NJ: Humana Press Inc. 2003. p. 145-161. Contact: Available from Humana Press Inc. 999 Riverview Drive, Suite 208, Totowa, NJ 07512. (973) 256-1699. Fax (973) 256-8341. E-mail:
[email protected]. Website: www.humanapress.com. PRICE: $165.00; plus shipping and handling. ISBN: 896039315. Summary: The increasing incidence of diabetes worldwide has prompted a rapid growth in the pace of scientific discovery and clinical understanding of this disease. This chapter on the prevention and correction of hypoglycemia is from a book in which wellrecognized physicians and researchers review the latest thinking about the causes of type 1 diabetes and the best approaches to treating both its acute and chronic complications. The author discusses the clinical context of hypoglycemia (low blood glucose) in diabetes, the physiological prevention or correction of hypoglycemia, clinical risk factors for hypoglycemia, the pathophysiology of glucose counterregulation in diabetes, and hypoglycemia risk reduction in diabetes. The author notes that improving glycemic control while minimizing hypoglycemia in diabetes requires both application of the principles of aggressive therapy (patient education and empowerment, frequent self-monitoring of blood glucose, flexible insulin regimens, individualized glycemic goals, ongoing professional guidance and support) and implementation of hypoglycemia risk reduction. 3 figures. 1 table. 75 references.
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Solving Hypoglycemia Problems Source: in Touchette, N. Diabetes Problem Solver. Alexandria, VA: American Diabetes Association. 1999. p. 91-104. Contact: Available from American Diabetes Association (ADA). Order Fulfillment Department, P.O. Box 930850, Atlanta, GA 31193-0850. (800) 232-6733. Fax (770) 4429742. Website: www.diabetes.org. PRICE: $19.95 for members; plus shipping and handling. ISBN: 1570400091. Summary: This chapter deals with solving hypoglycemia problems in people who have diabetes. This condition occurs when there is too little glucose in the blood. Hypoglycemia may occur when something happens to make insulin act more rapidly, when a person does not eat enough food or does not eat at the right time, when exercise or activity uses up too much glucose, or when a person consumes alcohol or uses other drugs. The chapter provides the reader with information on who is at risk for hypoglycemia; the symptoms of mild, moderate, and severe hypoglycemia; what the
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immediate course of action should be for dealing with hypoglycemia; how mild, moderate, and severe hypoglycemia should be treated; and how to prevent hypoglycemia that results from insulin irregularities, inadequate nutrition, exercise, sexual activity, attempts to avoid morning hypoglycemia, sleeping late, and alcohol consumption. Other topics discussed include managing hypoglycemia in the elderly; managing and preventing hypoglycemia associated with intensive diabetes therapy; and recognizing, handling, treating, and preventing hypoglycemia unawareness. •
Glucose Homeostasis and Hypoglycemia Source: in Wilson, J.D., et al., eds. Williams Textbook of Endocrinology. 9th ed. Philadelphia, PA: W.B. Saunders Company. 1998. p. 939-971. Contact: Available from W.B. Saunders Company. Book Order Fulfillment Department. 11830 Westline Industrial Drive, Saint Louis, MO 63146-9988. (800) 545-2522 or (314) 4537010. Fax (800) 568-5136 or (314) 453-7095. E-mail:
[email protected]. Website: www.wbsaunders.com. PRICE: $150.00 plus shipping and handling. ISBN: 0721661521. Summary: This chapter focuses on glucose homeostasis and hypoglycemia. The chapter begins with a discussion of the physiology of systemic glucoregulation, including glucose metabolism; the effect of fasting, feeding, and exercise on systemic glucose balance; hormonal, neural, and substrate glucoregulatory factors; and glucose counterregulation. Topics related to glucose metabolism include the origin and fate of glucose, hepatic glucose metabolism, and glucose utilization. Other topics include the control of glucoregulatory factors, the correction and prevention of hypoglycemia, and the principles of glucose counterregulation. The chapter next examines the pathophysiology of hypoglycemia, focusing on the clinical manifestations of hypoglycemia, the diagnosis of hypoglycemia, postabsorptive versus postprandial hypoglycemia, and the clinical classification of hypoglycemia. This is followed by a discussion of hypoglycemia in type 1 and type 2 diabetes. Topics related to hypoglycemia in type 1 diabetes include the frequency, impact, prevention, and treatment of hypoglycemia and the risk factors for this condition. The chapter continues with a discussion of the causes of postabsorptive hypoglycemia including drugs such as insulin or a sulfonylurea; hepatic, cardiac, and renal diseases, sepsis, and inanition; cortisol and growth hormone deficiencies and glucagon and epinephrine deficiencies; nonbeta cell tumors; and endogenous hyperinsulinism. Causes of hypoglycemia unique to infancy or childhood include transient intolerance of fasting, maternal diabetes, and enzymatic defects. Final topics include postprandial hypoglycemia, treatment of postabsorptive hypoglycemia, and care of the patient with suspected hypoglycemia. 22 figures. 3 tables. 391 references.
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Nutrition, Diabetes, and Hypoglycemia Source: in Whitney, E.N., Cataldo, C.B., and Rolfes, S.R. Understanding Normal and Clinical Nutrition. 4th ed. St. Paul, MN: West Publishing Company. 1994. p. 842-878. Contact: Available from West Publishing. 620 Opperman Drive, St. Paul, MN 55164. (800) 340-9378 or (612) 687-7000. PRICE: $67.00. ISBN: 0314041788. Summary: This chapter from a nutrition textbook covers nutrition, diabetes, and hypoglycemia. Topics include insulin-dependent and noninsulin-dependent diabetes (IDDM and NIDDM, respectively); diabetes-related disorders; the acute and chronic complications of diabetes; treatment for IDDM, including measuring glucose control, insulin, diet, physical activity, treating hyperglycemia and hypoglycemia, and special issues for children and elderly people with diabetes; treatment of NIDDM, including the
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crucial role of diet; treatment of diabetes during pregnancy, including IDDM and NIDDM during pregnancy, as well as gestational diabetes; reactive and fasting hypoglycemia; the treatment of hypoglycemia; and nutrition assessment. The chapter concludes with study questions, clinical application questions, and a 'highlight' of one patient with IDDM, focusing on the practical questions of incorporating all the diabetes management information into the reality of daily living. 1 figure. 9 tables. 15 references. •
Overview of Hypoglycemia Source: in Lincoln, T.A.; Eaddy, J.A. Beating the Blood Sugar Blues. Alexandria, VA: American Diabetes Association. 2001. p.1-9. 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: $12.95 plus shipping and handling. ISBN: 1580400485. Summary: This chapter is from a book that offers first hand knowledge from two doctors who have more than 100 years of combined experienced with the day-to-day balancing act of blood glucose (sugar) and diabetes. The authors, both of whom have type 1 diabetes, share their own stories as well as those of over 40 of their patients. This introductory chapter offers an overview of hypoglycemia (low blood glucose levels). The authors first review the physiology of the pancreas and normal blood glucose (sugar) levels, then explain how hypoglycemia can develop in people with type 1 or type 2 diabetes. When the patient has taken too much insulin or has used up glucose faster than normal in work or exercise, their blood glucose may fall low enough to cause them problems. People have a variety of symptoms associated with hypoglycemia, depending on how rapidly the blood glucose falls and how low it gets. The chapter covers these symptoms, the causes or factors that contribute to low blood glucose, risk factors, good management practices to prevent hypoglycemia, treatment of hypoglycemia (self care), and the occurrence of hypoglycemia in people who do not have diabetes and are not taking medications to lower blood glucose. 1 table.
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Alcohol and Hypoglycemia Source: in Lincoln, T.A.; Eaddy, J.A. Beating the Blood Sugar Blues. Alexandria, VA: American Diabetes Association. 2001. p.114-119. 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: $12.95 plus shipping and handling. ISBN: 1580400485. Summary: This chapter on alcohol and hypoglycemia (low blood glucose levels) is from a book that offers first hand knowledge from two doctors who have more than 100 years of combined experienced with the day-to-day balancing act of blood glucose (sugar) and diabetes. The authors, both of whom have type 1 diabetes, share their own stories as well as those of over 40 of their patients. In this chapter, the authors focus on how alcohol can interfere with the management of diabetes and also cause the person with diabetes to miss the symptoms of dropping blood glucose. The authors also discuss the caloric content of alcohol, behavioral changes with alcohol use, differentiating between the influences of alcohol and the symptoms of hypoglycemia, and the effect of alcohol on the complications of diabetes, including diabetic eye disease (retinopathy) and nerve disease (neuropathy). 1 table.
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Prescription Drugs and Hypoglycemia Source: in Lincoln, T.A.; Eaddy, J.A. Beating the Blood Sugar Blues. Alexandria, VA: American Diabetes Association. 2001. p.120-127. 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: $12.95 plus shipping and handling. ISBN: 1580400485. Summary: This chapter on prescription drugs and hypoglycemia (low blood glucose levels) is from a book that offers first hand knowledge from two doctors who have more than 100 years of combined experienced with the day-to-day balancing act of blood glucose (sugar) and diabetes. The authors, both of whom have type 1 diabetes, share their own stories as well as those of over 40 of their patients. In this chapter, the authors stress that patients must be in charge of their own health care and take the responsibility for keeping their health care providers up to date on whatever prescription (and non prescription) medications they are currently taking. In addition, when a new prescription is given, patients should always ask whether this new medication can be expected to have any effect on their diabetes control. Patients should carry an up-to-date list of all the medications they are taking and the dosage schedule in their wallet or pocketbook. It can be of great value for emergency physicians to be able to learn quickly what medications are being taken. The authors list ways to prevent hypoglycemia from medications; offer suggestions for handling medications at home and for making sure one gets the correct prescription in the first place; note medications that cause release of insulin, that reduce insulin resistance, and that slow the absorption of sugar; and reiterate the dangers of drug interactions and how drug effects can mask the symptoms of approaching hypoglycemia. 4 tables.
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Effects of Hypoglycemia on Nerves and Vision Source: in Lincoln, T.A.; Eaddy, J.A. Beating the Blood Sugar Blues. Alexandria, VA: American Diabetes Association. 2001. p.128-132. 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: $12.95 plus shipping and handling. ISBN: 1580400485. Summary: This chapter on the effects of hypoglycemia (low blood glucose levels) on nerves and vision is from a book that offers first hand knowledge from two doctors who have more than 100 years of combined experienced with the day-to-day balancing act of blood glucose (sugar) and diabetes. The authors, both of whom have type 1 diabetes, share their own stories as well as those of over 40 of their patients. In this chapter, the authors describe how certain brain functions may temporarily work poorly during hypoglycemia and cause alarming symptoms, varying from widespread stroke-like effects to weakness in just one group of muscles. Convulsions or uncontrollable jerking motions of the body occur in 10 to 20 percent of adults and even more frequently in children when they have a severe hypoglycemic episode. The authors discuss other neurologic problems that can be associated with hypoglycemia, including double vision, problems reading, and impaired color vision. People with diabetes under poor control and with resulting consistently high blood glucose levels may also develop blurred vision.
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Traveling and Hypoglycemia Source: in Lincoln, T.A.; Eaddy, J.A. Beating the Blood Sugar Blues. Alexandria, VA: American Diabetes Association. 2001. p.108-113. 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: $12.95 plus shipping and handling. ISBN: 1580400485. Summary: This chapter on traveling and hypoglycemia (low blood glucose levels) is from a book that offers first hand knowledge from two doctors who have more than 100 years of combined experienced with the day-to-day balancing act of blood glucose (sugar) and diabetes. The authors, both of whom have type 1 diabetes, share their own stories as well as those of over 40 of their patients. In this chapter, the authors note that travel offers many opportunities for the best plans to go awry. Meals may not be on time, menu choices may be limited, opportunities for exercise could be greatly reduced, and support people like family, friends, or work associated may not be available to help. The authors discuss the importance of planning ahead, wearing a medical alert tag or bracelet, being careful about preventing hypoglycemia during sleep, dealing with jet lag, and handling the extra exercise that may occur during travel.
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Low Blood Sugar (Hypoglycemia or Insulin Reaction) Source: in Chase, H.P. Understanding Insulin-Dependent Diabetes. 8th ed. Denver, CO: Barbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences Center. Children's Diabetes Foundation at Denver. 1995. p. 19-29. Contact: Available from Guild of the Children's Diabetes Foundation at Denver. 777 Grant Street, Suite 302, Denver, CO 80203. (800) 695-2873 or (303) 863-1200. PRICE: $10 (as of 1996). Summary: This chapter, from a book for families of children with insulin-dependent diabetes (IDDM), covers hypoglycemia or low blood glucose. The book is designed for use with the doctor and the diabetes team or alone as a 'refresher' course once the basic ideas are understood. The chapter covers the causes of hypoglycemia, the symptoms of hypoglycemia, recognizing low blood glucose levels, a false reaction, treatment for hypoglycemia, the use of glucagon, rebounding (reactive hypoglycemia or Somogyi reaction), the importance of adequate record keeping, preventing insulin reactions, and the need for medical identification. The chapter concludes with a list of definitions and a how-to sheet on giving glucagon injections. The book features the cartoon character, the Pink Panther, to depict many of the concepts and to serve as a narrator. 1 figure. 2 tables.
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Endocrine Emergencies: Hypoglycemic and Hyperglycemic Crises Source: in Clark, O.H. and Duh, Q. Textbook of Endocrine Surgery. Philadelphia, PA: W.B. Saunders Company. 1997. p. 651-661. 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: $155.00. ISBN: 0721658822. Summary: This chapter, from a book on endocrine surgery, provides health professionals with a review of the pathophysiology of hypoglycemic and hyperglycemic crises, which are seen most commonly in patients with diabetes. Such endocrine
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emergencies can be life-threatening and are encountered with some frequency in the surgical setting. Topics include the physiology of systemic glucose homeostasis, hormonal regulation of glucose metabolism, and management of the surgical patient with diabetes. For both hypoglycemic and hyperglycemic crises, the authors discuss clinical presentation, pathogenesis, and recommended therapy. Hypoglycemic crises may be due to diabetic ketoacidosis or a hyperglycemic hyperosmolar nonketotic state. Hypoglycemic crises are classified as postprandial hypoglycemia or fasting hypoglycemia. In most surgical patients, endocrine crises are due primarily to inadequate or excessive insulin secretion or administration; patients with diabetes are at particular risk. Appropriate monitoring of glucose levels and management with intravenous saline, insulin, and glucose are fundamental to treatment. 3 figures. 1 table. 62 references. (AA-M). •
Helping Patients Understand and Recognize Hypoglycemia Source: in Anderson, B.J. and Rubin, R.R., eds. Practical Psychology for Diabetes Clinicians: How to Deal with the Key Behavioral Issues Faced by Patients and Health Care Teams. Alexandria, VA: American Diabetes Association. 1996. p. 83-92. Contact: Available from American Diabetes Association. Order Fulfillment Department, P.O. Box 930850, Atlanta, GA 31193-0850. (800) 232-6733. Fax (404) 442-9742. PRICE: $19.95 (members); $24.95 (nonmembers). ISBN: 0945448732. Summary: This chapter, from a guidebook on behavioral issues for diabetes clinicians, provides a framework for helping patients understand and recognize hypoglycemia. The authors discuss the problem of hypoglycemia and its psychosocial consequences, hypoglycemic symptoms, and hypoglycemia unawareness. Topics include mild versus severe hypoglycemia; the fear of hypoglycemia; autonomic and neuroglycopenic symptoms; risk factors for hypoglycemia; hypoglycemia and mood changes; and psychological barriers to hypoglycemic symptom perception. The authors stress that, because both the type and intensity of hypoglycemic symptoms vary from patient to patient, it is important to help patients identify their own best warning cues. 6 tables. 3 references.
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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.
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Approach to the Patient with Hypoglycemia Source: Kelley, W.N., ed. Textbook of Internal Medicine. 3rd ed. Vol 2. Philadelphia, PA: Lippincott-Raven Publishers. 1997. p. 2166-2168. 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 therapeutic approach to hypoglycemia in adults. Topics include etiology, signs and symptoms, differential diagnosis, and strategies for optimal care management. The author points out that evaluation of suspected hypoglycemia requires consideration of both blood glucose level and the presence or absence of associated symptoms. Classifying specific disorders as reactive (occurring between 1 and 5 hours after eating) or fasting (occurring more than 5 hours afterwards) is the first step in approaching a diagnosis and understanding the underlying pathophysiologic mechanism. Differential diagnosis is usually not difficult after consideration of the individual patient's history and the clinical setting. In many cases, the probable diagnosis is apparent and it is possible to initiate appropriate therapy and conduct confirmatory tests. Clinical management of reactive hypoglycemia favors prevention of future episodes over emergency treatment of a single episode, which is often mild and transient. Patients with various causes of fasting hypoglycemia may have extremely low blood glucose levels that require immediate intervention. Definitive treatment of fasting hypoglycemia is determined by the specific underlying disease. 2 tables. 5 references. (AA-M).
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Hypoglycemic Agents Source: in Adler, S.N., et al. Pocket Manual of Differential Diagnosis. 3rd ed. Boston, MA: Little, Brown and Company. 1994. p. 86-89. Contact: Available from Lippincott-Raven Publishers. 12107 Insurance Way, Hagerstown, MD 21740-5184. (800) 777-2295. Fax (301) 824-7390. E-mail:
[email protected]. Website: http://www.lrpub.com. PRICE: $24.95. ISBN: 0316011096. Summary: This section is from a chapter outlining pharmaceutical agents in a pocket manual of differential diagnosis; the section focuses on hypoglycemic agents. The section begins with a table listing the characteristics of commonly used insulin preparations. The next page presents a table noting the different types, availability, dosage, and duration of action of oral hypoglycemic agents (sulfonylureas). The section concludes with listings of factors causing hyperglycemia and factors causing hypoglycemia in people with diabetes. References for further reading follow each entry. 2 references.
•
Hypoglycemic Disorders Source: in Hall, J.E.; Nieman, L.K., eds. Handbook of Diagnostic Endocrinology. Totowa, NJ: The Humana Press, Inc. 2003. p. 193-211. Contact: Humana Press, Inc. 999 Riverview Dr., Suite 208 Totowa, NJ 07512. (973) 2561699. Fax (973) 256-8341. E-mail:
[email protected] PRICE: $99.50 plus shipping and handling. ISBN: 0896037576.
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Summary: With the rapid development of new and more reliable diagnostic tests, and aided by the molecular and genetic approaches that continue to deepen the understanding of these diseases, the ability to diagnose patients with endocrine disease has dramatically increased. This chapter on hypoglycemic (low blood glucose) disorders is from a book that explains the pathophysiology and clinical manifestations of endocrine disorders and surveys all the latest laboratory tests used in their diagnosis. The author discusses classification of hypoglycemic disorders, and then considers the tests available for their diagnostic evaluation. The author notes that a healthy-appearing patient with no coexisting disease who has a history of neuroglycopenic spells requires an approach quite different from that taken for a patient with concurrent illness or a hospitalized patient with acute hypoglycemia (low levels of blood glucose). Tests discussed include serum glucose levels, the prolonged (72 hour) fast, the mixed meal test, the C-peptide suppression test, insulin antibodies, glycated hemoglobin, and imaging studies. 6 figures. 4 tables. 84 references.
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CHAPTER 8. MULTIMEDIA ON HYPOGLYCEMIA Overview In this chapter, we show you how to keep current on multimedia sources of information on hypoglycemia. 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 hypoglycemia is the Combined Health Information Database. You will need to limit your search to “Videorecording” and “hypoglycemia” 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 “hypoglycemia” (or synonyms) into the “For these words:” box. The following is a typical result when searching for video recordings on hypoglycemia: •
Managing Diabetic Hypoglycemia Source: Alexandria, VA: American Diabetes Association. 2001. (videorecording). Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. E-mail:
[email protected]. Fax: (770) 4429742. Website: www.diabetes.org. PRICE: $29.95. ISBN: 580401597. Summary: Hypoglycemic (low blood glucose) episodes can happen anywhere, anytime. They are frightening and can, indeed, be life-threatening. This upbeat videotape presents diabetes facts on how to prevent, identify and treat mild, moderate and severe hypoglycemia (low blood sugar reactions). This video is for people with diabetes, their family, friends, teachers, coaches and fellow employees. The video explains low blood sugar or insulin reactions for teachers, relatives, babysitters, and siblings. This video vividly portrays the mild, moderate, and severe forms of hypoglycemia. The program notes the symptoms and portrays the reactions in simple, clear, non-technical language. The program also explores the causes of low blood sugar and how to prevent them. Key
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instructors are: H. Peter Chase, M.D., Professor of Pediatrics, Barbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences Center and American Diabetes Association 2001 Physician of the Year; Robert Eckel, M.D. Professor of Medicine, University of Colorado Health Sciences Center; Kathy Jensen, RD, CDE. In addition, a wide variety of people with diabetes and parents of children with diabetes share their experiences and perspectives.
Audio Recordings The Combined Health Information Database contains abstracts on audio productions. To search CHID, go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find audio 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 “Sound Recordings.” Type “hypoglycemia” (or synonyms) into the “For these words:” box. The following is a typical result when searching for sound recordings on hypoglycemia: •
Bernstein Plan: Type I Source: Van Nuys, CA: Prana Publications. 1995. (audiocassettes). Contact: Available from Prana Publications. 5623 Matilija Avenue, Van Nuys, CA 91401. (800) 735-7726 or (818) 780-1308. Fax (818) 786-7359. E-Mail
[email protected]. PRICE: $22.95 plus $3.25 shipping and handling (as of 1995). Order Number A04. Summary: These audiocassette tapes familiarize listeners with Dr. R.K. Bernstein's method of diabetes control. Dr. Bernstein, who has had insulin-dependent diabetes for 49 years, believes high blood sugar causes diabetes complications and that complications can be prevented and at times reversed by normalizing blood sugar. He keeps his patients' blood glucose levels between 85 and 105 by severely limiting carbohydrates in the diet. Topics on the tapes include the low carbohydrate diet; muscle building; multiple blood glucose tests; multiple small doses of insulin; preventing hypoglycemia; managing sick days; and gastroparesis. (AA-M).
•
Serving Individuals with Diabetes who are Blind or Visually Impaired: A Resource Guide for Vocational Rehabilitation Counselors Source: Mississippi State, MS: Rehabilitation Research and Training Center on Blindness and Low Vision, Mississippi State University. 1997. 227 p. Contact: Available from Rehabilitation Research and Training Center on Blindness and Low Vision, Mississippi State University. Publications Manager, P.O. Drawer 6189, Mississippi State, MS 39762. (601) 325-2001 or (601) 325-8693. Fax (601) 325-8989. TDD (601) 325-8693. PRICE: $25.00 in any format. Summary: This resource guide is designed to help counselors better serve individuals with diabetes who are blind or visually impaired. The guide refers readers to a large collection of resources on various diabetes publications, medications, and appliances. Five sections cover an introduction to diabetes; self management; current medical issues; employment issues; and emotional aspects of diabetes. Topics include myths about diabetes; diabetic eye disease; new nutrition guidelines for diabetes management; oral diabetes medications; diabetes and medications; insulin and measurement devices and systems; maintaining the proper temperature of insulin; blood glucose control; 'talking' blood glucose monitoring systems; and noninvasive glucose monitors. The authors also
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discuss diabetes and the feet; kidney failure, dialysis, and transplantation; pancreas transplantation; arthritis and diabetes; diabetes and yeast infections; hypoglycemia; diabetic peripheral neuropathy; diabetes and men's sexual health; cardiovascular health; diabetic ketoacidosis; diabetic dermopathy; diabetes and the Individualized Written Rehabilitation Program (IWRP); the use of Braille; health insurance; and scleral shells. The book's appendix includes lists of diabetes-related organizations, publications, listservs, and World Wide Web sites; sources of low-sugar products and products for the blind; and diabetes equipment and supplies, including insulin syringe magnifiers. The resource guide is available in large print, Braille, audiocassette, and computer diskette. •
Diabetes and How You Can Manage It Easily Source: San Diego, CA: H L Enterprises. 1993. (audiocassettes). Contact: Available from H L Enterprises. 12730 Carmel Country Road, Number 120, San Diego, CA 92130. (619) 792-8837. PRICE: $33.00. Summary: This set of four audiocassettes is designed to provide an overview of diabetes mellitus and its care. Topics include the importance of attitude; meal planning and food habits; medicines and exercise; and blood glucose, including monitoring and understanding hypoglycemia and hyperglycemia. The accompanying outline includes information on resources for further information.
Bibliography: Multimedia on Hypoglycemia The National Library of Medicine is a rich source of information on healthcare-related multimedia productions including slides, computer software, and databases. To access the multimedia database, go to the following Web site: http://locatorplus.gov/. Select “Search LOCATORplus.” Once in the search area, simply type in hypoglycemia (or synonyms). Then, in the option box provided below the search box, select “Audiovisuals and Computer Files.” From there, you can choose to sort results by publication date, author, or relevance. The following multimedia has been indexed on hypoglycemia: •
Advances in hypoglycemia medications [videorecording] Source: School of Nursing, University of Minnesota; Year: 1975; Format: Videorecording; Minneapolis: The University, [1975]
•
Alcoholic hypoglycemia [videorecording] Source: Emory University School of Medicine; Year: 1974; Format: Videorecording; Atlanta:Georgia Regional Medical Television Network: [for loan or sale by A. W. Calhoun Medical Library, /1974]
•
Death from burning fat [videorecording]: too little, hypoglycemia Source: Reye syndrome; too much, ketoacidosis / Office of Research Services, Medical Arts and Photography Branch; Year: 2003; Format: Videorecording; [Bethesda, Md.: National Institutes of Health, 2003]
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Hypoglycemia [slide] Source: Michael S. Kappy, Elmer S. Lightner, Bruce R. Herrick; produced by Medical Audiovisual Services, University of Arizona, Health Sciences Center; Year: 1976; Format: Slide; Tucson, Ariz.: The Center: [for sale by its Biomedical Communications], c1976
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Hypoglycemia [slide] Source: produced by the Aultman Hospital Media Center; Pamela E. Carylon, author; Year: 1982; Format: Slide; Canton, Ohio: The Center, [1982]
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Hypoglycemia [videorecording] Source: School of Nursing, University of Minnesota; Year: 1975; Format: Videorecording; Minneapolis: The University, [1975]
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Hypoglycemia and the infant of the diabetic mother [videorecording] Source: produced by Medical Educational Resources Program, Indiana University, School of Medicine; Year: 1981; Format: Videorecording; Indianapolis, Ind.: The Program, 1981
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Hypoglycemia in the newborn [slide] Source: developed at an NMAC Workshop under the auspices of The Audiovisual Committee of the Association of Medical School Pediatric Department Chairmen; Year: 1973; Format: Slide; Atlanta: National Medical Audiovisual Center, 1973
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Hypoglycemias of infancy [videorecording] Source: [presented by] the University of Texas Medical School at Houston; produced by UT/TV Houston, the University of Texas Health Science Center at Houston; Year: 1989; Format: Videorecording; [Houston, Tex.]: UT/TV Houston, c1989
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Hypoglycemic disorders [videorecording] Source: Marshfield Clinic, Saint Joseph's Hospital; a presentation of the Marshfield Video Network; Year: 1996; Format: Videorecording; Marshfield, WI: The Clinic, [1996]
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Medications and hypoglycemia [videorecording] Source: Health Communications Network, Division of Continuing Education, Medical University of S.C. in Charleston; Year: 1980; Format: Videorecording; Charleston, S.C.: The Division, c1980
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New concepts in neonatal hypoglycemia [videorecording] Source: the University of Texas Medical School at Houston; produced by UT/TV, Houston; Year: 1991; Format: Videorecording; [Houston, Tex.: UT-TV], c1991
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CHAPTER 9. PERIODICALS AND NEWS ON HYPOGLYCEMIA Overview In this chapter, we suggest a number of news sources and present various periodicals that cover hypoglycemia.
News Services and Press Releases One of the simplest ways of tracking press releases on hypoglycemia 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 “hypoglycemia” (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 hypoglycemia. 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 “hypoglycemia” (or synonyms). The following was recently listed in this archive for hypoglycemia: •
Alprazolam curbs responses to hypoglycemic stress Source: Reuters Medical News Date: September 23, 2003
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Long-acting insulin Lantus lowers glucose without hypoglycemia risk Source: Reuters Medical News Date: August 25, 2003
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Aventis's Lantus insulin lowers glucose without hypoglycemia risk Source: Reuters Industry Breifing Date: August 25, 2003
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CORRECTION: Theophylline's effect on unawareness of hypoglycemia sustained over long term Source: Reuters Medical News Date: August 04, 2003
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Insulin glargine reduces risk of nocturnal hypoglycemia in type 2 diabetics Source: Reuters Medical News Date: June 18, 2003
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Diabetics show muted response to hypoglycemia during sleep Source: Reuters Medical News Date: May 30, 2003
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Hypoglycemia a risk factor for cardiac ischemia in type 2 diabetics with CAD Source: Reuters Medical News Date: May 26, 2003
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Exercise-induced hypoglycemia might be widespread Source: Reuters Medical News Date: February 10, 2003
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Islet transplantation fails to restore hypoglycemic hormonal counterregulation Source: Reuters Medical News Date: December 24, 2002
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Nocturnal hypoglycemia frequent in children with type 1 diabetes Source: Reuters Medical News Date: December 17, 2002
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Hypoglycemia risk linked with intensive insulin therapy and glucose monitoring Source: Reuters Medical News Date: December 05, 2001
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Nightcap ups risk of low blood sugar in diabetics Source: Reuters Health eLine Date: October 25, 2001
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Metformin combined with insulin does not affect awareness of hypoglycemia Source: Reuters Industry Breifing Date: October 03, 2001
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Low blood sugar shortens attention span: report Source: Reuters Health eLine Date: September 26, 2001
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Serious hypoglycemia is rare in patients with type 2 diabetes Source: Reuters Medical News Date: July 10, 2001
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Increased beta-adrenergic sensitivity restores hypoglycemia awareness in diabetes Source: Reuters Medical News Date: May 01, 2001
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Long-acting insulin lowers risk of nocturnal hypoglycemia in type 2 diabetics Source: Reuters Medical News Date: April 27, 2001
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Infant hypoglycemia risk increases with valproate exposure in utero Source: Reuters Industry Breifing Date: September 21, 2000
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Octreotide can be first-line treatment for sulfonylurea-induced hypoglycemia Source: Reuters Medical News Date: July 26, 2000
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Caffeine consumption increases intensity of hypoglycemic warning symptoms Source: Reuters Medical News Date: April 25, 2000
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Sulfonylurea use increases risk of prolonged hypoglycemia in end-stage renal disease Source: Reuters Medical News Date: March 22, 2000
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Low blood sugar impairs diabetic drivers Source: Reuters Health eLine Date: February 10, 2000
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Insulin analog reduces nocturnal hypoglycemia in type 1 diabetics Source: Reuters Medical News Date: October 11, 1999
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Nocturnal hypoglycemia prevalent among young diabetics on standard therapy Source: Reuters Medical News Date: August 27, 1999
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Many diabetics opt to drive during perceived and actual hypoglycemia Source: Reuters Medical News Date: August 25, 1999 The NIH
Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine. Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name. Market Wire Market Wire is more focused on technology than the other wires. To browse the latest press releases by topic, such as alternative medicine, biotechnology, fitness, healthcare, legal, nutrition, and pharmaceuticals, access Market Wire’s Medical/Health channel at http://www.marketwire.com/mw/release_index?channel=MedicalHealth. Or simply go to
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Market Wire’s home page at http://www.marketwire.com/mw/home, type “hypoglycemia” (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 “hypoglycemia” (or synonyms). If you know the name of a company that is relevant to hypoglycemia, 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 “hypoglycemia” (or synonyms).
Newsletter Articles Use the Combined Health Information Database, and limit your search criteria to “newsletter articles.” Again, you will need to use the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. Go to the bottom of the search page where “You may refine your search by.” Select the dates and language that you prefer. For the format option, select “Newsletter Article.” Type “hypoglycemia” (or synonyms) into the “For these words:” box. You should check back periodically with this database as it is updated every three months. The following is a typical result when searching for newsletter articles on hypoglycemia: •
Hypoglycemia and the Decision to Drive Source: Diabetes Care in Nova Scotia. 10(2): 1-2. April 2000. Contact: Available from Diabetes Care Program of Nova Scotia. P.O. Box 9000, 1278 Tower Road, Bethune Building, Suite 577, Halifax, Nova Scotia B3H 2Y9. (902) 473-3219. Fax (902) 473-3911. E-mail:
[email protected]. Summary: This article presents scientific evidence of driver impairment under conditions of hypoglycemia. In one study, participants were instructed to record certain data at the same time they were monitoring their blood glucose or at any time they felt their blood glucose was low. The study found that 50 percent decided they could drive even when they estimated their blood glucose to be significantly low. In another study, the effect on driving performance with progressive degrees of hypoglycemia was tested. The study found impairment in driving ability at low blood glucose levels. In addition, many participants knew or perceived their blood glucose was low, but they failed to take appropriate action. These studies confirm the Canadian recommendation for commercial drivers to test their blood glucose before driving and to treat low blood
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glucose. Although the studies underscore the need for appropriate education, they should not be interpreted as a need to impede the acquisition of a license for people who have diabetes. 4 tables. 5 references.
Academic Periodicals covering Hypoglycemia Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to hypoglycemia. In addition to these sources, you can search for articles covering hypoglycemia that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”
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CHAPTER 10. RESEARCHING MEDICATIONS Overview While a number of hard copy or CD-ROM resources are available for researching medications, a more flexible method is to use Internet-based databases. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.
U.S. Pharmacopeia Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications recommended for hypoglycemia. One such source is the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the U.S. Pharmacopeia (USP). Today, the USP is a non-profit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at http://www.usp.org/. The USP currently provides standards for over 3,700 medications. The resulting USP DI® Advice for the Patient® can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database, located at http://www.fda.gov/cder/da/da.htm. While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopeia (USP). Below, we have compiled a list of medications associated with hypoglycemia. If you would like more information on a particular medication, the provided hyperlinks will direct you to ample documentation (e.g. typical dosage, side effects, drug-interaction risks, etc.). The
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following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to hypoglycemia: Antidiabetic Agents, Sulfonylurea •
Systemic - U.S. Brands: Amaryl; DiaBeta; Diabinese; Dymelor; Glucotrol; Glucotrol XL; Glynase PresTab; Micronase; Orinase; Tolinase http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202742.html
Diazoxide •
Oral - U.S. Brands: Proglycem http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202191.html
Insulin •
Systemic - U.S. Brands: Humulin 50/50; Humulin 70/30; Humulin 70/30 Pen; Humulin L; Humulin N; Humulin N Pen; Humulin R; Humulin R, Regular U500 (Concentrated); Humulin U; Lente; Lente Iletin II; Novolin 70/30; Novolin 70/30 PenFill; Novolin 70/30 Prefilled; Novolin L; Novoli http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203298.html
Octreotide •
Systemic - U.S. Brands: Sandostatin http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202421.html
Commercial Databases In addition to the medications listed in the USP above, a number of commercial sites are available by subscription to physicians and their institutions. Or, you may be able to access these sources from your local medical library.
Mosby’s Drug Consult™ Mosby’s Drug Consult™ database (also available on CD-ROM and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Subscription information is available at the following hyperlink: http://www.mosbysdrugconsult.com/. PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html.
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Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee. If you have any questions about a medical treatment, the FDA may have an office near you. Look for their number in the blue pages of the phone book. You can also contact the FDA through its toll-free number, 1-888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.
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APPENDICES
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APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.
NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute12: •
Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm
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National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/
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National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html
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National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25
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National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm
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National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm
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National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375
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National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/
12
These publications are typically written by one or more of the various NIH Institutes.
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•
National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm
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National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/
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National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm
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National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm
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National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/
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National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/
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National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm
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National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html
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National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm
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National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm
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National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm
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National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html
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National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm
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Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp
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National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/
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National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp
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Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html
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Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm
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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.13 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:14 •
Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html
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HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html
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NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html
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Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/
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Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html
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Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html
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Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/
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Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html
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Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html
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Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html
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MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html
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Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 14 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 Combined Health Information Database
A comprehensive source of information on clinical guidelines written for professionals is the Combined Health Information Database. You will need to limit your search to one of the following: Brochure/Pamphlet, Fact Sheet, or Information Package, and “hypoglycemia” using the “Detailed Search” option. Go directly to the following hyperlink: 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 the publication date, select “All Years.” Select your preferred language and the format option “Fact Sheet.” Type “hypoglycemia” (or synonyms) into the “For these words:” box. The following is a sample result: •
Reassessment of External Insulin Infusion Pumps Source: Rockville, MD: Agency for Health Care Policy and Research. 1991. 12 p. Contact: Available from Agency for Health Care Policy and Research. Division of Information and Publications, 5600 Fishers Lane, Parklawn Building, Room 18-12, Rockville, MD 20857. (301) 443-4100. PRICE: Single copy free. Order Number: DHHS Pub. No. AHCPR 91-0030. Summary: Continuous subcutaneous insulin infusion (CSII) therapy using external infusion pumps provides an alternative to multiple daily injections (MDI) for people with insulin-dependent diabetes mellitus (IDDM) who require intensive insulin therapy. This report presents a reassessment of external insulin infusion pumps. The benefits cited for people on CSII include greater lifestyle flexibility with regard to meal timing, work, and recreational scheduling. The higher risks associated with CSII such as diabetic ketoacidosis, hypoglycemia, and skin problems may be averted with improvements in the mechanical design of CSII devices. The authors conclude that the overall clinical evidence indicates that CSII is as effective as MDI in attaining normoglycemia in people with IDDM who require intensive insulin therapy. 1 table. 44 references. (AA-M).
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Self-Monitoring of Blood Glucose Source: Diabetes Care. 17(1): 81-86. January 1994. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: This article discusses the consensus statement arising from a Consensus Development Conference on Self-Monitoring of Blood Glucose (SMBG), held in September 1993. The conference consisted of 24 invited presentations and contributions from a large audience of health care professionals and representatives from industry. The consensus panel reached a consensus on the answers to five questions: What is the epidemiology of SMBG?; Who should self-monitor?; What is the current technology?; How should the data obtained from self-monitoring be used?; and What is the future of
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self-monitoring? This article briefly reports on each of these five areas. Specific topics include the achievement and maintenance of a specific level of glycemic control; the prevention and detection of hypoglycemia; the avoidance of severe hyperglycemia; adjusting care in response to changes in life-style; determining the need for initiating insulin therapy in gestational diabetes mellitus (GDM); measurement principles and limitations of SMBG systems; performance of SMBG systems; the assessment of clinically significant error; and quality assurance. 10 references. •
Diabetes: Diet Source: New York, NY: Nidus Information Services, Inc. 1994. 8 p. Contact: Available from Nidus Information Services, Inc. 175 Fifth Avenue, Suite 2338, New York, NY 10010. (800) 334-9355 or (212) 260-4268. PRICE: $5.95 if mailed first class; $9.95 if faxed (as of 1995). Bulk discounts available. Summary: This wellness publication aids readers in understanding current medical knowledge and diabetes. As part of a series of reports, it uses a question-and-answer format to discuss various topics, including why people with diabetes require special diets, the general guidelines for a diabetes diet, exchange lists, meal planning or schedules, the use of sodium and alcohol, food labels, and weighing and measuring foods. The document discusses behavioral considerations in diabetes management such as blood glucose monitoring, preventing hypoglycemia, and weight control. The document concludes with an annotated list of resource organizations, through which readers can obtain additional information. 11 tables. 6 references.
The NLM Gateway15 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.16 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “hypoglycemia” (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
15 16
Items Found 22361 181 148 33 7 22730
Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.
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).
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HSTAT17 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.18 These documents include clinical practice guidelines, quickreference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.19 Simply search by “hypoglycemia” (or synonyms) at the following Web site: http://text.nlm.nih.gov.
Coffee Break: Tutorials for Biologists20 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.21 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.22 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.
Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are some examples that may interest you: •
CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.
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Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.
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Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html.
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The HSTAT URL is http://hstat.nlm.nih.gov/.
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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. 20 Adapted from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html. 21 The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 22 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process.
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The Genome Project and Hypoglycemia In the following section, we will discuss databases and references which relate to the Genome Project and hypoglycemia. Online Mendelian Inheritance in Man (OMIM) The Online Mendelian Inheritance in Man (OMIM) database is a catalog of human genes and genetic disorders authored and edited by Dr. Victor A. McKusick and his colleagues at Johns Hopkins and elsewhere. OMIM was developed for the World Wide Web by the National Center for Biotechnology Information (NCBI).23 The database contains textual information, pictures, and reference information. It also contains copious links to NCBI’s Entrez database of MEDLINE articles and sequence information. To search the database, go to http://www.ncbi.nlm.nih.gov/Omim/searchomim.html. Type “hypoglycemia” (or synonyms) into the search box, and click “Submit Search.” If too many results appear, you can narrow the search by adding the word “clinical.” Each report will have additional links to related research and databases. In particular, the option “Database Links” will search across technical databases that offer an abundance of information. The following is an example of the results you can obtain from the OMIM for hypoglycemia: •
Glucagon Deficiency, Hypoglycemia due to Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?231530
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Hypoglycemia, Hypoketotic, with Deficiency of Carnitine Palmitoyltransferase I Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?255120
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Hypoglycemia, Hypoketotic, with Deficiency of Carnitine Palmitoyltransferase Ii Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?600649
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Hypoglycemia, Leucine-induced Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?240800
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Hypoglycemia, Neonatal, Simulating Foetopathia Diabetica Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?240900
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Persistent Hyperinsulinemic Hypoglycemia of Infancy Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?601820 Genes and Disease (NCBI - Map)
The Genes and Disease database is produced by the National Center for Biotechnology Information of the National Library of Medicine at the National Institutes of Health. This Web site categorizes each disorder by system of the body. Go to http://www.ncbi.nlm.nih.gov/disease/, and browse the system pages to have a full view of important conditions linked to human genes. Since this site is regularly updated, you may wish to revisit it from time to time. The following systems and associated disorders are addressed: 23 Adapted from http://www.ncbi.nlm.nih.gov/. Established in 1988 as a national resource for molecular biology information, NCBI creates public databases, conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information--all for the better understanding of molecular processes affecting human health and disease.
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Cancer: Uncontrolled cell division. Examples: Breast and ovarian cancer, Burkitt lymphoma, chronic myeloid leukemia, colon cancer, lung cancer, malignant melanoma, multiple endocrine neoplasia, neurofibromatosis, p53 tumor suppressor, pancreatic cancer, prostate cancer, Ras oncogene, RB: retinoblastoma, von Hippel-Lindau syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Cancer.html
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Immune System: Fights invaders. Examples: Asthma, autoimmune polyglandular syndrome, Crohn’s disease, DiGeorge syndrome, familial Mediterranean fever, immunodeficiency with Hyper-IgM, severe combined immunodeficiency. Web site: http://www.ncbi.nlm.nih.gov/disease/Immune.html
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Metabolism: Food and energy. Examples: Adreno-leukodystrophy, atherosclerosis, Best disease, Gaucher disease, glucose galactose malabsorption, gyrate atrophy, juvenile-onset diabetes, obesity, paroxysmal nocturnal hemoglobinuria, phenylketonuria, Refsum disease, Tangier disease, Tay-Sachs disease. Web site: http://www.ncbi.nlm.nih.gov/disease/Metabolism.html
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Muscle and Bone: Movement and growth. Examples: Duchenne muscular dystrophy, Ellis-van Creveld syndrome, Marfan syndrome, myotonic dystrophy, spinal muscular atrophy. Web site: http://www.ncbi.nlm.nih.gov/disease/Muscle.html
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Nervous System: Mind and body. Examples: Alzheimer disease, amyotrophic lateral sclerosis, Angelman syndrome, Charcot-Marie-Tooth disease, epilepsy, essential tremor, fragile X syndrome, Friedreich’s ataxia, Huntington disease, Niemann-Pick disease, Parkinson disease, Prader-Willi syndrome, Rett syndrome, spinocerebellar atrophy, Williams syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Brain.html
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Signals: Cellular messages. Examples: Ataxia telangiectasia, Cockayne syndrome, glaucoma, male-patterned baldness, SRY: sex determination, tuberous sclerosis, Waardenburg syndrome, Werner syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Signals.html
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Transporters: Pumps and channels. Examples: Cystic fibrosis, deafness, diastrophic dysplasia, Hemophilia A, long-QT syndrome, Menkes syndrome, Pendred syndrome, polycystic kidney disease, sickle cell anemia, Wilson’s disease, Zellweger syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Transporters.html Entrez
Entrez is a search and retrieval system that integrates several linked databases at the National Center for Biotechnology Information (NCBI). These databases include nucleotide sequences, protein sequences, macromolecular structures, whole genomes, and MEDLINE through PubMed. Entrez provides access to the following databases: •
3D Domains: Domains from Entrez Structure, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo
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Books: Online books, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=books
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Genome: Complete genome assemblies, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Genome
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NCBI’s Protein Sequence Information Survey Results: Web site: http://www.ncbi.nlm.nih.gov/About/proteinsurvey/
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Nucleotide Sequence Database (Genbank): Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Nucleotide
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OMIM: Online Mendelian Inheritance in Man, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM
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PopSet: Population study data sets, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Popset
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ProbeSet: Gene Expression Omnibus (GEO), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo
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Protein Sequence Database: Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Protein
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PubMed: Biomedical literature (PubMed), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed
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Structure: Three-dimensional macromolecular structures, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Structure
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Taxonomy: Organisms in GenBank, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Taxonomy
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To access the Entrez system at the National Center for Biotechnology Information, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=genome, and then select the database that you would like to search. The databases available are listed in the drop box next to “Search.” Enter “hypoglycemia” (or synonyms) into the search box and click “Go.” Jablonski’s Multiple Congenital Anomaly/Mental Retardation (MCA/MR) Syndromes Database24 This online resource has been developed to facilitate the identification and differentiation of syndromic entities. Special attention is given to the type of information that is usually limited or completely omitted in existing reference sources due to space limitations of the printed form. At http://www.nlm.nih.gov/mesh/jablonski/syndrome_toc/toc_a.html, you can search across syndromes using an alphabetical index. Search by keywords at http://www.nlm.nih.gov/mesh/jablonski/syndrome_db.html.
24
Adapted from the National Library of Medicine: http://www.nlm.nih.gov/mesh/jablonski/about_syndrome.html.
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The Genome Database25 Established at Johns Hopkins University in Baltimore, Maryland in 1990, the Genome Database (GDB) is the official central repository for genomic mapping data resulting from the Human Genome Initiative. In the spring of 1999, the Bioinformatics Supercomputing Centre (BiSC) at the Hospital for Sick Children in Toronto, Ontario assumed the management of GDB. The Human Genome Initiative is a worldwide research effort focusing on structural analysis of human DNA to determine the location and sequence of the estimated 100,000 human genes. In support of this project, GDB stores and curates data generated by researchers worldwide who are engaged in the mapping effort of the Human Genome Project (HGP). GDB’s mission is to provide scientists with an encyclopedia of the human genome which is continually revised and updated to reflect the current state of scientific knowledge. Although GDB has historically focused on gene mapping, its focus will broaden as the Genome Project moves from mapping to sequence, and finally, to functional analysis. To access the GDB, simply go to the following hyperlink: http://www.gdb.org/. Search “All Biological Data” by “Keyword.” Type “hypoglycemia” (or synonyms) into the search box, and review the results. If more than one word is used in the search box, then separate each one with the word “and” or “or” (using “or” might be useful when using synonyms).
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Adapted from the Genome Database: http://gdbwww.gdb.org/gdb/aboutGDB.html - mission.
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APPENDIX B. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. Since new guidelines on hypoglycemia can appear at any moment and be published by a number of sources, the best approach to finding guidelines is to systematically scan the Internet-based services that post them.
Patient Guideline Sources The remainder of this chapter directs you to sources which either publish or can help you find additional guidelines on topics related to hypoglycemia. 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 hypoglycemia. 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 “hypoglycemia”:
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Guides on hypoglycemia Hypoglycemia http://www.nlm.nih.gov/medlineplus/hypoglycemia.html Hypoglycemia http://www.nlm.nih.gov/medlineplus/tutorials/hypoglycemialoader.html
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Other guides Diabetes http://www.nlm.nih.gov/medlineplus/diabetes.html Diabetes and Meal Planning http://www.nlm.nih.gov/medlineplus/tutorials/diabetesandmealplanningloader.t ml Diabetes and Pregnancy http://www.nlm.nih.gov/medlineplus/diabetesandpregnancy.html Diabetic Diet http://www.nlm.nih.gov/medlineplus/diabeticdiet.html Diabetic Nerve Problems http://www.nlm.nih.gov/medlineplus/diabeticnerveproblems.html Endocrine Diseases http://www.nlm.nih.gov/medlineplus/endocrinediseases.html Islet Cell Transplantation http://www.nlm.nih.gov/medlineplus/isletcelltransplantation.html Juvenile Diabetes http://www.nlm.nih.gov/medlineplus/juvenilediabetes.html Pancreas Transplantation http://www.nlm.nih.gov/medlineplus/pancreastransplantation.html
Within the health topic page dedicated to hypoglycemia, the following was listed: •
Diagnosis/Symptoms Glucose Tests Source: American Association for Clinical Chemistry http://www.labtestsonline.org/understanding/analytes/glucose/test.html
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Specific Conditions/Aspects Are Low Blood Sugars Dangerous? Source: Joslin Diabetes Center http://www.joslin.harvard.edu/education/library/low_bs_danger.shtml Hyperinsulinemia Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=HQ00896
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What Can I Do to Prevent Serious Hypoglycemic Episodes When I Am Hypoglycemic Unaware? Source: Joslin Diabetes Center http://www.joslin.harvard.edu/education/library/hypoglycemic_unaware.shtml What Is Hypoglycemia? (Low Blood Sugar) Source: American Diabetes Association http://www.diabetes.org/type2/medical/hypoglycemia/default.jsp •
Children Ketotic Hypoglycemia in Infants Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=AN00302
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Organizations American Diabetes Association http://www.diabetes.org/ National Institute of Diabetes and Digestive and Kidney Diseases http://www.niddk.nih.gov/
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 hypoglycemia. 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: •
How to Handle Low Blood Sugar Source: Patient Care. 33(8): 41. April 30, 1999. Contact: Available from Medical Economics. 5 Paragon Drive, Montvale, NJ 07645. (800) 432-4570. Fax (201) 573-4956. Summary: This article provides people who have diabetes with general guidelines on managing low blood sugar. Symptoms include shakiness, nervousness, dizziness, weakness, and irritability. Suggestions on managing low blood sugar include treating it immediately, wearing a medical identification bracelet, preparing for long drives or trips, informing one's doctor about all drugs being taken, and using alcohol only after
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consulting a doctor. The article also lists good sources of carbohydrates to treat low blood sugar. •
Recognizing and Treating Low Blood Sugar Source: Minneapolis, MN: International Diabetes Center. 1994. 11 p. Contact: Available from International Diabetes Center. Attention: IDC Publishing, 3800 Park Nicollet Boulevard, Minneapolis, MN 55416. (612) 993-3874. PRICE: $1.95. ISBN: 1885115059. Summary: This booklet reviews the basics of recognizing and treating low blood glucose, or hypoglycemia. Sections address recognition of hypoglycemia, including symptoms, pseudo-hypoglycemia, and hypoglycemic unawareness; treatment, including carbohydrate, glucose gels, and glucagon; and prevention, including blood glucose testing (SMBG), exercise, schedule changes, and precautions for drivers. The authors conclude by reiterating the importance of continual preparedness for hypoglycemic reactions and remind readers of the importance of medical alert identification. One chart lists the levels of hypoglycemia and the symptoms and recommended treatment for each level.
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Low Blood Sugar Source: San Diego, CA: Linda Vista Health Care Center. 1992. 2 p. Contact: Available from Linda Vista Health Care Center. 6973 Linda Vista Road, San Diego, CA 92111. (619) 279-0925. PRICE: Single copy free. Reproduction is allowed. Summary: This brief patient education brochure reviews the problems of low blood glucose. Written in easy-to-understand language, the brochure defines low blood glucose, explains when and how it can happen, lists the symptoms, and gives suggestions for treating a hypoglycemic reaction. A final section reminds readers of steps to take to avoid problems with low blood glucose. Simple line drawings accompany each point presented. This brochure is also available in Laotian (see DMBR01846) and Vietnamese (see DMBR01847).
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Questions Most Frequently Asked About Hypoglycemia Source: Washington, D.C.: Sugar Association, Inc. 1993. 4 p. Contact: Available from Sugar Association, Inc. 1101 15th Street, N.W., Suite 600, Washington, D.C. 20005. (202) 785-1122. PRICE: Up to 100 copies free. Summary: This brochure, written in a question-and-answer format, discusses hypoglycemia. The brochure addresses the causes of hypoglycemia; how hypoglycemia is treated; the use of special diets; how to find out if low blood glucose is causing symptoms; how blood glucose is measured; low blood glucose levels; the incidence of hypoglycemia; the use of oral glucose tolerance tests (OGTT); hypoglycemia in diabetes; how blood glucose levels are controlled; and steps to take if a reader suspects he or she has hypoglycemia.
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Hypoglycemia (Low Blood Glucose) Source: Cleveland, OH: Diabetes Association of Greater Cleveland. 2002. 2 p.
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Contact: Available from Diabetes Association of Greater Cleveland. 3601 South Green Road Suite 100, Cleveland, Ohio 44122. (216) 591-0800 Fax (216) 591-0320. E-mail:
[email protected]. Website: www.dagc.org. PRICE: Single copy free. Summary: This fact sheet describes hypoglycemia, low blood glucose levels, a common problem associated with diabetes. The fact sheet defines hypoglycemia, then notes mild, moderate, and severe symptoms of the problem. The fact sheet stresses that it is important to treat hypoglycemia when symptoms are mild to moderate. Simple treatment options are outlined. The fact sheet then discusses the causes of hypoglycemia, how it can be prevented, and what people with diabetes can do to prepare for coping with hypoglycemia. The fact sheet concludes with the contact information for the Diabetes Association of Greater Cleveland (www.dagc.org). 2 tables. •
Diabetes Hypoglycemia Source: in Griffith, H.W. Instructions for Patients. 5th ed. Philadelphia, PA: W.B. Saunders Company. 1994. p. 119. Contact: Available from W.B. Saunders Company. Book Order Fulfillment, 6277 Sea Harbor Drive, Orlando, FL 32887-4430. (800) 545-2522. Fax (800) 874-6418. PRICE: $49.95. ISBN: 0721649300 (English); 0721669972 (Spanish). Summary: This fact sheet on diabetes hypoglycemia is from a compilation of instructions for patients, published in book format. The fact sheet provides information in three sections: basic information, including a description of the condition, frequent signs and symptoms, causes, risk factors, preventive measures, expected outcome, and possible complications; treatment, including general measures, medication, activity guidelines, and diet; and when to contact one's health care provider. The fact sheet can be photocopied and distributed to patients as a reinforcement of oral instructions and as a teaching tool. The book in which the fact sheet appears is available in English or Spanish.
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Hypoglycemia Source: Bethesda, MD: National Diabetes Information Clearinghouse (NDIC). 2002. 6 p. Contact: Available from National Diabetes Information Clearinghouse (NDIC). 1 Information Way, Bethesda, MD 20892-3560. (800) 860-8747 or (301) 654-3327. E-mail:
[email protected]. PRICE: Full-text available online at no charge; single copy free; bulk copies available. Order number: DM-167. Summary: This fact sheet provides an overview of hypoglycemia. The fact sheet covers the following topics: a definition of hypoglycemia; how the body controls glucose; the symptoms of hypoglycemia; normal blood glucose ranges; hypoglycemia in diabetes; other causes of hypoglycemia; diagnostic tests used to confirm hypoglycemia; reactive hypoglycemia; rare causes of hypoglycemia; and research activities in this area. The fact sheet provides a brief annotated list of resource organizations, including the American Diabetes Association, the American Dietetic Association, the Juvenile Diabetes Foundation International, and the National Diabetes Information Clearinghouse. A list of readings is also included. The fact sheet concludes with a brief description of the work of the National Diabetes Information Clearinghouse. 10 references.
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Treating Hypoglycemia and How to Avoid It Source: Alexandria, VA: American Diabetes Association. 199x. 4 p.
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Contact: Available from American Diabetes Association, Inc. Order Fulfillment Department, P.O. Box 930850, Atlanta, GA 31193-0850. (800) 232-6733. Fax (770) 4429742. PRICE: $9.95 (members), $11.95 (nonmembers) for 50 copies; single copy free. Order number CDBD18. Summary: This fact sheet, which is one in a series of 42 fact sheets about daily living and coping with diabetes, provides information on hypoglycemia (low blood glucose reaction). Topics include causes of hypoglycemia, tight control, treating hypoglycemia, the value of carbohydrates, hypoglycemia unawareness, and preventing hypoglycemia. The fact sheet notes that a person who is experiencing hypoglycemia and recognizes the symptoms immediately should first test his or her blood glucose and then consume 15 grams (one half of an ounce) of carbohydrate if necessary. In order to prevent insulin reactions, the fact sheet suggests following meal plans carefully, testing blood glucose levels frequently, and taking diabetes medications at the correct times and in the right amounts. A sidebar lists amounts of particular foods which provide 15 grams of carbohydrates. (AA-M). •
Hypoglycemia: Low Blood Sugar Source: Lexington, KY: Lexington-Fayette County Health Department. 1995. 2 p. Contact: Available from Lexington-Fayette County Health Department. Division of Nutrition and Health Education, 650 Newtown Pike, Lexington, KY 40508. (606) 2882333. Fax (606) 288-2359. PRICE: $15.00 per 50 copies plus shipping. Summary: This general introduction to hypoglycemia (low blood glucose) is one in a series of 22 diabetes education materials that combine practical tips and humorous drawings with current diabetes information. The series is written at a sixth grade reading level and is designed to teach and motivate patients to take care of themselves. The fact sheet provides a description of the causes of hypoglycemia, including too little food, not eating on time, too much insulin or diabetes pills, exercising harder or longer than usual, and drinking alcohol. The fact sheet illustrates how people may feel when their blood glucose levels are low, including shaky, anxious, numb fingers, fast heartbeat, dizzy, weak, tired, irritable, sweaty, hungry, and with a headache. The fact sheet provides practical recommendations for dealing with hypoglycemia, including steps to take to prevent it from becoming worse. One section briefly reviews the impact of diabetic neuropathy on the person's ability to sense a low blood glucose reaction.
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How to Recognize and Manage Hypoglycemia in Diabetes Source: Consultant. 36(11): 2363-2364. November 1996. Contact: Reprints available from Consultant Health Guide. Cliggott Publishing Company, 55 Holly Hill Lane, Box 4010, Greenwich, CT 06831-0010. Fax (203) 661-8163. Summary: This health guide is designed to give people with diabetes a basic overview of how to recognize and manage hypoglycemia (low blood glucose levels). The article describes the symptoms of hypoglycemia, including feeling shaky, anxious, and hungry; experiencing confusion or loss of consciousness; or having a seizure. The article also recommends treating symptoms of hypoglycemia with a sufficient amount of carbohydrate, such as that in glucose tablets, fruit juice, or skim milk. The article also describes the use of glucagon kits, used by a friend or family member if the person with diabetes becomes unconscious from hypoglycemia. The article concludes with a note about automobile driving for people who experience hypoglycemia; the author reminds readers that the only way hypoglycemia is likely to cause a death is if it occurs while the
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person with diabetes is driving. The article includes blank space for the provider to individualize patient instructions before giving a copy of the article to the patient. •
Warning Signs: Is It Hypoglycemia? Source: South Deerfield, MA: Channing L. Bete Co., Inc. 1999. [4 p.]. Contact: Available from Channing L. Bete, Co., Inc. 200 State Road, South Deerfield, MA 01373-0200. (800) 628-7733. Fax (800) 499-6464. PRICE: $1.05 each; plus shipping and handling; quantity discounts available. Order number 30514. Summary: This pamphlet provides people who have diabetes with information on hypoglycemia. This condition, which is most common among people who take insulin, occurs when blood sugar becomes too low. Causes of hypoglycemia include not eating enough, not eating at one's usual time, exercising more than usual, taking too much insulin, and consuming too much alcohol. Warning signs include shakiness, nervousness, irritability, sweating, dizziness, tiredness, hunger, rapid heartbeat, and headache. Emergency signs of severe hypoglycemia include being uncooperative or disoriented, having seizures, and losing consciousness. The pamphlet explains how to recognize the signs of both hypoglycemia and severe hypoglycemia.
•
Reactive and Fasting Hypoglycemia Source: Minneapolis, MN: International Diabetes Center. 1998. 4 p. Contact: Available from International Diabetes Center. Park Nicollet HealthSource. 3800 Park Nicollet Boulevard, Minneapolis, MN 55416. (800) 372-7776 or (612) 993-3534. Fax (612) 993-1840. PRICE: $1.00 for one copy; $0.90 each for 10 copies; $0.80 each for 100 copies; $0.70 for 500 copies; plus shipping and handling. ISBN: 1885115474. Summary: This pamphlet uses a question and answer format to provide information on reactive and fasting hypoglycemia. It defines hypoglycemia, lists the causes and symptoms of hypoglycemia, presents the features of fasting and reactive hypoglycemia, and explains how the symptoms of hypoglycemia can be avoided and how hypoglycemia is treated. Eating habits that may help avoid the symptoms of hypoglycemia include eating 5 to 6 small meals or snacks each day, spreading one's intake of carbohydrate foods throughout the day, avoiding foods that contain large amounts of carbohydrate, avoiding beverages and foods containing caffeine, and limiting or avoiding alcoholic beverages. The pamphlet highlights good food choices and foods to use less often in the categories of starches, fruit, milk, vegetables, meat and meat substitutes, fats and oils, beverages, and other. It also presents a sample menu that provides approximately 1,550 calories among three meals and two snacks.
Healthfinder™ Healthfinder™ is sponsored by the U.S. Department of Health and Human Services and offers links to hundreds of other sites that contain healthcare information. This Web site is located at http://www.healthfinder.gov. Again, keyword searches can be used to find guidelines. The following was recently found in this database:
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•
Hypoglycemia Summary: Hypoglycemia, or low blood sugar, occurs when blood levels of glucose drop too low to fuel the body's activity. Source: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=838 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 hypoglycemia. 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. NORD (The National Organization of Rare Disorders, Inc.) NORD provides an invaluable service to the public by publishing short yet comprehensive guidelines on over 1,000 diseases. NORD primarily focuses on rare diseases that might not be covered by the previously listed sources. NORD’s Web address is http://www.rarediseases.org/. A complete guide on hypoglycemia can be purchased from NORD for a nominal fee. PEDBASE Similar to NORD, PEDBASE covers relatively rare disorders, limited mainly to pediatric conditions. PEDBASE was designed by Dr. Alan Gandy. To access the database, which is more oriented to researchers than patients, you can view the current list of health topics covered at the following Web site: http://www.icondata.com/health/pedbase/pedlynx.htm. 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/
Patient Resources
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Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/
•
WebMD®Health: http://my.webmd.com/health_topics
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Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to hypoglycemia. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with hypoglycemia. 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 hypoglycemia. 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 “hypoglycemia” (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 “hypoglycemia”. 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 “hypoglycemia” (or synonyms) into the “For
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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 http://www.rarediseases.org/search/orgsearch.html. Type following Web site: “hypoglycemia” (or a synonym) into the search box, and click “Submit Query.”
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APPENDIX C. FINDING MEDICAL LIBRARIES Overview In this Appendix, we show you how to quickly find a medical library in your area.
Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.26
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
26
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)27: •
Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/
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Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)
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Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm
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California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html
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California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html
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California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html
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California: Gateway Health Library (Sutter Gould Medical Foundation)
•
California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/
•
California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp
•
California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html
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California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/
•
California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/
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California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/
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California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html
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California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/
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Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/
•
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/
27
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
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Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html
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Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm
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Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp
•
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
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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
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Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/
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Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/
•
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
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Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/
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Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/
•
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/
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Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html
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Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm
•
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/
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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/
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Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html
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Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm
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Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330
•
Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)
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National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html
•
National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/
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National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/
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•
Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm
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New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/
•
New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm
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New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm
•
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
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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
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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/
276 Hypoglycemia
•
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
277
ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •
ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html
•
MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp
•
Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/
•
Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html
•
On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/
•
Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp
•
Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm
Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a). The NIH suggests the following Web sites in the ADAM Medical Encyclopedia when searching for information on hypoglycemia: •
Basic Guidelines for Hypoglycemia Hypoglycemia Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000386.htm IDM Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001597.htm Insulin shock Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000386.htm
•
Signs & Symptoms for Hypoglycemia Cold sweats Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003216.htm Coma Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003202.htm
278 Hypoglycemia
Confusion Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003205.htm Consciousness, decreased Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003202.htm Convulsions Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003200.htm Dizziness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003093.htm Double vision Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003029.htm Eyes, pupils different size Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003314.htm Fainting Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003092.htm Fatigue Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003088.htm Hallucinations Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003258.htm Headache Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003024.htm Heartbeat sensations Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003081.htm Hunger Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003134.htm Irritability Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003214.htm Loss of consciousness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003202.htm Malaise Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003089.htm Memory loss Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003257.htm Muscle pain Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003178.htm
Online Glossaries 279
Paleness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003244.htm Rapid heart rate Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003077.htm Seizure Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003200.htm Seizures Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003200.htm Sleeping difficulty Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003210.htm Sweating, excessive Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003218.htm Trembling Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003192.htm •
Diagnostics and Tests for Hypoglycemia ALT Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003473.htm Blood glucose levels Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003482.htm Blood glucose monitoring Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003438.htm Blood sugar levels Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003482.htm Blood-glucose level Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003482.htm Blood-sugar levels Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003482.htm CSF collection Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003428.htm Glucagon Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003716.htm Glucose monitoring Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003438.htm Glucose tolerance test Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003466.htm
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Serum glucose Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003482.htm •
Nutrition for Hypoglycemia Complex carbohydrates Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002469.htm Fat Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002468.htm Fiber Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002470.htm Simple sugars Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002469.htm
•
Background Topics for Hypoglycemia Exercise Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001941.htm Incidence Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002387.htm Ingestion of alcohol Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001944.htm Unconsciousness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000022.htm
Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •
Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical
•
MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html
•
Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/
•
Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine
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HYPOGLYCEMIA DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 1-Propanol: A colorless liquid made by oxidation of aliphatic hydrocarbons that is used as a solvent and chemical intermediate. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Abdominal Pain: Sensation of discomfort, distress, or agony in the abdominal region. [NIH] Ablation: The removal of an organ by surgery. [NIH] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] Acetohexamide: A sulfonylurea hypoglycemic agent that is metabolized in the liver to 1hydrohexamide. [NIH] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Acidosis: A pathologic condition resulting from accumulation of acid or depletion of the alkaline reserve (bicarbonate content) in the blood and body tissues, and characterized by an increase in hydrogen ion concentration. [EU] Acquired Immunodeficiency Syndrome: An acquired defect of cellular immunity associated with infection by the human immunodeficiency virus (HIV), a CD4-positive Tlymphocyte count under 200 cells/microliter or less than 14% of total lymphocytes, and increased susceptibility to opportunistic infections and malignant neoplasms. Clinical manifestations also include emaciation (wasting) and dementia. These elements reflect criteria for AIDS as defined by the CDC in 1993. [NIH] Acuity: Clarity or clearness, especially of the vision. [EU] 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] Acute renal: A condition in which the kidneys suddenly stop working. In most cases, kidneys can recover from almost complete loss of function. [NIH] Adamantane: A tricyclo bridged hydrocarbon. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adaptation: 1. The adjustment of an organism to its environment, or the process by which it enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the
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intensity of light; the adjustment to such variations. 3. The decline in the frequency of firing of a neuron, particularly of a receptor, under conditions of constant stimulation. 4. In dentistry, (a) the proper fitting of a denture, (b) the degree of proximity and interlocking of restorative material to a tooth preparation, (c) the exact adjustment of bands to teeth. 5. In microbiology, the adjustment of bacterial physiology to a new environment. [EU] Adenine: A purine base and a fundamental unit of adenine nucleotides. [NIH] Adenocarcinoma: A malignant epithelial tumor with a glandular organization. [NIH] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adenosine Kinase: An enzyme that catalyzes the formation of ADP plus AMP from adenosine plus ATP. It can serve as a salvage mechanism for returning adenosine to nucleic acids. EC 2.7.1.20. [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] Adjuvant Therapy: Treatment given after the primary treatment to increase the chances of a cure. Adjuvant therapy may include chemotherapy, radiation therapy, or hormone therapy. [NIH]
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] Adolescent Nutrition: Nutrition of children aged 13-18 years. [NIH] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH] Adrenal Glands: Paired glands situated in the retroperitoneal tissues at the superior pole of each kidney. [NIH] Adrenal insufficiency: The reduced secretion of adrenal glands. [NIH] Adrenal Medulla: The inner part of the adrenal gland; it synthesizes, stores and releases catecholamines. [NIH] Adrenaline: A hormone. Also called epinephrine. [NIH] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adrenergic 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]
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Adsorption: The condensation of gases, liquids, or dissolved substances on the surfaces of solids. It includes adsorptive phenomena of bacteria and viruses as well as of tissues treated with exogenous drugs and chemicals. [NIH] Adsorptive: It captures volatile compounds by binding them to agents such as activated carbon or adsorptive resins. [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 Metabolism: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as aerobic respiration, oxidative metabolism, or cell respiration. [NIH] Aerobic Respiration: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as oxidative metabolism, cell respiration, or aerobic metabolism. [NIH] Aerosols: Colloids with a gaseous dispersing phase and either liquid (fog) or solid (smoke) dispersed phase; used in fumigation or in inhalation therapy; may contain propellent agents. [NIH]
Afferent: Concerned with the transmission of neural impulse toward the central part of the nervous system. [NIH] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Agar: A complex sulfated polymer of galactose units, extracted from Gelidium cartilagineum, Gracilaria confervoides, and related red algae. It is used as a gel in the preparation of solid culture media for microorganisms, as a bulk laxative, in making emulsions, and as a supporting medium for immunodiffusion and immunoelectrophoresis. [NIH]
Age Groups: Persons classified by age from birth (infant, newborn) to octogenarians and older (aged, 80 and over). [NIH] Age of Onset: The age or period of life at which a disease or the initial symptoms or manifestations of a disease appear in an individual. [NIH] Aged, 80 and Over: A person 80 years of age and older. [NIH] Aggressiveness: The quality of being aggressive (= characterized by aggression; militant; enterprising; spreading with vigour; chemically active; variable and adaptable). [EU] Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Agoraphobia: Obsessive, persistent, intense fear of open places. [NIH] Airways: Tubes that carry air into and out of the lungs. [NIH]
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Akathisia: 1. A condition of motor restlessness in which there is a feeling of muscular quivering, an urge to move about constantly, and an inability to sit still, a common extrapyramidal side effect of neuroleptic drugs. 2. An inability to sit down because of intense anxiety at the thought of doing so. [EU] Alanine: A non-essential amino acid that occurs in high levels in its free state in plasma. It is produced from pyruvate by transamination. It is involved in sugar and acid metabolism, increases immunity, and provides energy for muscle tissue, brain, and the central nervous system. [NIH] Albumin: 1. Any protein that is soluble in water and moderately concentrated salt solutions and is coagulable by heat. 2. Serum albumin; the major plasma protein (approximately 60 per cent of the total), which is responsible for much of the plasma colloidal osmotic pressure and serves as a transport protein carrying large organic anions, such as fatty acids, bilirubin, and many drugs, and also carrying certain hormones, such as cortisol and thyroxine, when their specific binding globulins are saturated. Albumin is synthesized in the liver. Low serum levels occur in protein malnutrition, active inflammation and serious hepatic and renal disease. [EU] Alertness: A state of readiness to detect and respond to certain specified small changes occurring at random intervals in the environment. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alimentary: Pertaining to food or nutritive material, or to the organs of digestion. [EU] Alkaline: Having the reactions of an alkali. [EU] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Allergens: Antigen-type substances (hypersensitivity, immediate). [NIH]
that
produce
immediate
hypersensitivity
Allograft: An organ or tissue transplant between two humans. [NIH] Alpha Cell: A type of cell in the pancreas (in areas called the islets of Langerhans). Alpha cells make and release a hormone called glucagon, which raises the level of glucose (sugar) in the blood. [NIH] Alpha-fetoprotein: AFP. A protein normally produced by a developing fetus. AFP levels are usually undetectable in the blood of healthy nonpregnant adults. An elevated level of AFP suggests the presence of either a primary liver cancer or germ cell tumor. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Ameliorating: A changeable condition which prevents the consequence of a failure or accident from becoming as bad as it otherwise would. [NIH] Amenorrhea: Absence of menstruation. [NIH] Amine: An organic compound containing nitrogen; any member of a group of chemical compounds formed from ammonia by replacement of one or more of the hydrogen atoms by
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organic (hydrocarbon) radicals. The amines are distinguished as primary, secondary, and tertiary, according to whether one, two, or three hydrogen atoms are replaced. The amines include allylamine, amylamine, ethylamine, methylamine, phenylamine, propylamine, and many other compounds. [EU] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino Acid Substitution: The naturally occurring or experimentally induced replacement of one or more amino acids in a protein with another. If a functionally equivalent amino acid is substituted, the protein may retain wild-type activity. Substitution may also diminish or eliminate protein function. Experimentally induced substitution is often used to study enzyme activities and binding site properties. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Aminoethyl: A protease inhibitor. [NIH] Aminopropionitrile: 3-Aminopropanenitrile. Reagent used as an intermediate in the manufacture of beta-alanine and pantothenic acid. [NIH] Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. [NIH] Amniocentesis: Percutaneous transabdominal puncture of the uterus during pregnancy to obtain amniotic fluid. It is commonly used for fetal karyotype determination in order to diagnose abnormal fetal conditions. [NIH] Amniotic Fluid: Amniotic cavity fluid which is produced by the amnion and fetal lungs and kidneys. [NIH] Amphetamine: A powerful central nervous system stimulant and sympathomimetic. Amphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulation of release of monamines, and inhibiting monoamine oxidase. Amphetamine is also a drug of abuse and a psychotomimetic. The l- and the d,l-forms are included here. The l-form has less central nervous system activity but stronger cardiovascular effects. The d-form is dextroamphetamine. [NIH] Amputation: Surgery to remove part or all of a limb or appendage. [NIH] Amygdala: Almond-shaped group of basal nuclei anterior to the inferior horn of the lateral ventricle of the brain, within the temporal lobe. The amygdala is part of the limbic system. [NIH]
Amylase: An enzyme that helps the body digest starches. [NIH] Amyloid: A general term for a variety of different proteins that accumulate as extracellular fibrils of 7-10 nm and have common structural features, including a beta-pleated sheet conformation and the ability to bind such dyes as Congo red and thioflavine (Kandel, Schwartz, and Jessel, Principles of Neural Science, 3rd ed). [NIH] Anaerobic: 1. Lacking molecular oxygen. 2. Growing, living, or occurring in the absence of molecular oxygen; pertaining to an anaerobe. [EU] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of
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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] Analeptic: A drug which acts as a restorative, such as caffeine, amphetamine, pentylenetetrazol, etc. [EU] Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Analytes: A component of a test sample the presence of which has to be demonstrated. The term "analyte" includes where appropriate formed from the analyte during the analyses. [NIH]
Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Androgens: A class of sex hormones associated with the development and maintenance of the secondary male sex characteristics, sperm induction, and sexual differentiation. In addition to increasing virility and libido, they also increase nitrogen and water retention and stimulate skeletal growth. [NIH] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Anesthetics: Agents that are capable of inducing a total or partial loss of sensation, especially tactile sensation and pain. They may act to induce general anesthesia, in which an unconscious state is achieved, or may act locally to induce numbness or lack of sensation at a targeted site. [NIH] Angina: Chest pain that originates in the heart. [NIH] Anginal: Pertaining to or characteristic of angina. [EU] Angiogenesis: Blood vessel formation. Tumor angiogenesis is the growth of blood vessels from surrounding tissue to a solid tumor. This is caused by the release of chemicals by the tumor. [NIH] Angiotensin converting enzyme inhibitor: A drug used to decrease pressure inside blood vessels. [NIH] Angiotensin-Converting Enzyme Inhibitors: A class of drugs whose main indications are the treatment of hypertension and heart failure. They exert their hemodynamic effect mainly by inhibiting the renin-angiotensin system. They also modulate sympathetic nervous system activity and increase prostaglandin synthesis. They cause mainly vasodilation and mild natriuresis without affecting heart rate and contractility. [NIH] 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] Anionic: Pertaining to or containing an anion. [EU] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Annealing: The spontaneous alignment of two single DNA strands to form a double helix. [NIH]
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Anomalies: Birth defects; abnormalities. [NIH] Anorexia: Lack or loss of appetite for food. Appetite is psychologic, dependent on memory and associations. Anorexia can be brought about by unattractive food, surroundings, or company. [NIH] Anorexia Nervosa: The chief symptoms are inability to eat, weight loss, and amenorrhea. [NIH]
Anoxia: Clinical manifestation of respiratory distress consisting of a relatively complete absence of oxygen. [NIH] Antagonism: Interference with, or inhibition of, the growth of a living organism by another living organism, due either to creation of unfavorable conditions (e. g. exhaustion of food supplies) or to production of a specific antibiotic substance (e. g. penicillin). [NIH] Antecedent: Existing or occurring before in time or order often with consequential effects. [EU]
Anterior Cerebral Artery: Artery formed by the bifurcation of the internal carotid artery. Branches of the anterior cerebral artery supply the caudate nucleus, internal capsule, putamen, septal nuclei, gyrus cinguli, and surfaces of the frontal lobe and parietal lobe. [NIH] Anterograde: Moving or extending forward; called also antegrade. [EU] 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] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Anticonvulsant: An agent that prevents or relieves convulsions. [EU] Antidiabetic: An agent that prevents or alleviates diabetes. [EU] Antidiabetic Agent: A substance that helps a person with diabetes control the level of glucose (sugar) in the blood so that the body works as it should. [NIH] Antidote: A remedy for counteracting a poison. [EU] Antiemetic: An agent that prevents or alleviates nausea and vomiting. Also antinauseant. [EU]
Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU]
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Antigen-presenting cell: APC. A cell that shows antigen on its surface to other cells of the immune system. This is an important part of an immune response. [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] Antineoplastic Agents: Substances that inhibit or prevent the proliferation of neoplasms. [NIH]
Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are highly reactive chemicals that often contain oxygen. They are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation. [NIH] Antipsychotic: Effective in the treatment of psychosis. Antipsychotic drugs (called also neuroleptic drugs and major tranquilizers) are a chemically diverse (including phenothiazines, thioxanthenes, butyrophenones, dibenzoxazepines, dibenzodiazepines, and diphenylbutylpiperidines) but pharmacologically similar class of drugs used to treat schizophrenic, paranoid, schizoaffective, and other psychotic disorders; acute delirium and dementia, and manic episodes (during induction of lithium therapy); to control the movement disorders associated with Huntington's chorea, Gilles de la Tourette's syndrome, and ballismus; and to treat intractable hiccups and severe nausea and vomiting. Antipsychotic agents bind to dopamine, histamine, muscarinic cholinergic, a-adrenergic, and serotonin receptors. Blockade of dopaminergic transmission in various areas is thought to be responsible for their major effects : antipsychotic action by blockade in the mesolimbic and mesocortical areas; extrapyramidal side effects (dystonia, akathisia, parkinsonism, and tardive dyskinesia) by blockade in the basal ganglia; and antiemetic effects by blockade in the chemoreceptor trigger zone of the medulla. Sedation and autonomic side effects (orthostatic hypotension, blurred vision, dry mouth, nasal congestion and constipation) are caused by blockade of histamine, cholinergic, and adrenergic receptors. [EU] Antipyretic: An agent that relieves or reduces fever. Called also antifebrile, antithermic and febrifuge. [EU] Anuria: Inability to form or excrete urine. [NIH] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Anxiolytic: An anxiolytic or antianxiety agent. [EU] Aorta: The main trunk of the systemic arteries. [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] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the
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pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Appendicitis: Acute inflammation of the vermiform appendix. [NIH] Approximate: Approximal [EU] Aqueous: Having to do with water. [NIH] Arcuate Nucleus: A nucleus located in the middle hypothalamus in the most ventral part of the third ventricle near the entrance of the infundibular recess. Its small cells are in close contact with the ependyma. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Aromatic: Having a spicy odour. [EU] Arrhythmia: Any variation from the normal rhythm or rate of the heart beat. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Arteriolosclerosis: Sclerosis and thickening of the walls of the smaller arteries (arterioles). Hyaline arteriolosclerosis, in which there is homogeneous pink hyaline thickening of the arteriolar walls, is associated with benign nephrosclerosis. Hyperplastic arteriolosclerosis, in which there is a concentric thickening with progressive narrowing of the lumina may be associated with malignant hypertension, nephrosclerosis, and scleroderma. [EU] 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] Arteriovenous: Both arterial and venous; pertaining to or affecting an artery and a vein. [EU] Articular: Of or pertaining to a joint. [EU] Aspartate: A synthetic amino acid. [NIH] Aspartic: The naturally occurring substance is L-aspartic acid. One of the acidic-amino-acids is obtained by the hydrolysis of proteins. [NIH] Aspartic Acid: One of the non-essential amino acids commonly occurring in the L-form. It is found in animals and plants, especially in sugar cane and sugar beets. It may be a neurotransmitter. [NIH] Asphyxia: A pathological condition caused by lack of oxygen, manifested in impending or actual cessation of life. [NIH] Aspiration: The act of inhaling. [NIH] Aspirin: A drug that reduces pain, fever, inflammation, and blood clotting. Aspirin belongs to the family of drugs called nonsteroidal anti-inflammatory agents. It is also being studied in cancer prevention. [NIH]
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Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Astrocytes: The largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the blood brain barrier. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with microglia) respond to injury. Astrocytes have high- affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitter, but their role in signaling (as in many other functions) is not well understood. [NIH] Asymptomatic: Having no signs or symptoms of disease. [NIH] Ataxia: Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharnyx, larnyx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. [NIH] Atrial: Pertaining to an atrium. [EU] Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] Attenuated: Strain with weakened or reduced virulence. [NIH] Auditory: Pertaining to the sense of hearing. [EU] Autacoids: A chemically diverse group of substances produced by various tissues in the body that cause slow contraction of smooth muscle; they have other intense but varied pharmacologic activities. [NIH] Autoantibodies: Antibodies that react with self-antigens (autoantigens) of the organism that produced them. [NIH] Autoantigens: Endogenous tissue constituents that have the ability to interact with autoantibodies and cause an immune response. [NIH] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Autoimmunity: Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by autoimmune diseases. [NIH] Automobile Driving: The effect of environmental or physiological factors on the driver and driving ability. Included are driving fatigue, and the effect of drugs, disease, and physical disabilities on driving. [NIH] Autonomic: Self-controlling; functionally independent. [EU] Autonomic Nervous System: The enteric, parasympathetic, and sympathetic nervous systems taken together. Generally speaking, the autonomic nervous system regulates the internal environment during both peaceful activity and physical or emotional stress. Autonomic activity is controlled and integrated by the central nervous system, especially the hypothalamus and the solitary nucleus, which receive information relayed from visceral afferents; these and related central and sensory structures are sometimes (but not here) considered to be part of the autonomic nervous system itself. [NIH] Autonomic Neuropathy: A disease of the nerves affecting mostly the internal organs such as
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the bladder muscles, the cardiovascular system, the digestive tract, and the genital organs. These nerves are not under a person's conscious control and function automatically. Also called visceral neuropathy. [NIH] Autosuggestion: Suggestion coming from the subject himself. [NIH] Axonal: Condition associated with metabolic derangement of the entire neuron and is manifest by degeneration of the distal portion of the nerve fiber. [NIH] Back Pain: Acute or chronic pain located in the posterior regions of the trunk, including the thoracic, lumbar, sacral, or adjacent regions. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacterial Physiology: Physiological processes and activities of bacteria. [NIH] Bactericidal: Substance lethal to bacteria; substance capable of killing bacteria. [NIH] Bacteriophage: A virus whose host is a bacterial cell; A virus that exclusively infects bacteria. It generally has a protein coat surrounding the genome (DNA or RNA). One of the coliphages most extensively studied is the lambda phage, which is also one of the most important. [NIH] Baroreflex: A negative feedback system which buffers short-term changes in blood pressure. Increased pressure stretches blood vessels which activates pressoreceptors (baroreceptors) in the vessel walls. The net response of the central nervous system is a reduction of central sympathetic outflow. This reduces blood pressure both by decreasing peripheral vascular resistance and by lowering cardiac output. Because the baroreceptors are tonically active, the baroreflex can compensate rapidly for both increases and decreases in blood pressure. [NIH]
Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] Basal Ganglia Diseases: Diseases of the basal ganglia including the putamen; globus pallidus; claustrum; amygdala; and caudate nucleus. Dyskinesias (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include cerebrovascular disease; neurodegenerative diseases; and craniocerebral trauma. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Basement Membrane: Ubiquitous supportive tissue adjacent to epithelium and around smooth and striated muscle cells. This tissue contains intrinsic macromolecular components such as collagen, laminin, and sulfated proteoglycans. As seen by light microscopy one of its subdivisions is the basal (basement) lamina. [NIH] Basophils: Granular leukocytes characterized by a relatively pale-staining, lobate nucleus and cytoplasm containing coarse dark-staining granules of variable size and stainable by basic dyes. [NIH] Behavior Therapy: The application of modern theories of learning and conditioning in the treatment of behavior disorders. [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]
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Bewilderment: Impairment or loss of will power. [NIH] Bilateral: Affecting both the right and left side of body. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bilirubin: A bile pigment that is a degradation product of heme. [NIH] Binding Sites: The reactive parts of a macromolecule that directly participate in its specific combination with another molecule. [NIH] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biogenesis: The origin of life. It includes studies of the potential basis for life in organic compounds but excludes studies of the development of altered forms of life through mutation and natural selection, which is evolution. [NIH] Biogenic Amines: A group of naturally occurring amines derived by enzymatic decarboxylation of the natural amino acids. Many have powerful physiological effects (e.g., histamine, serotonin, epinephrine, tyramine). Those derived from aromatic amino acids, and also their synthetic analogs (e.g., amphetamine), are of use in pharmacology. [NIH] Biological response modifier: BRM. A substance that stimulates the body's response to infection and disease. [NIH] Biological therapy: Treatment to stimulate or restore the ability of the immune system to fight infection and disease. Also used to lessen side effects that may be caused by some cancer treatments. Also known as immunotherapy, biotherapy, or biological response modifier (BRM) therapy. [NIH] Biological Transport: The movement of materials (including biochemical substances and drugs) across cell membranes and epithelial layers, usually by passive diffusion. [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] Bivalent: Pertaining to a group of 2 homologous or partly homologous chromosomes during the zygotene stage of prophase to the first metaphase in meiosis. [NIH] Bladder: The organ that stores urine. [NIH] Blastocyst: The mammalian embryo in the post-morula stage in which a fluid-filled cavity, enclosed primarily by trophoblast, contains an inner cell mass which becomes the embryonic disc. [NIH] Bloating: Fullness or swelling in the abdomen that often occurs after meals. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Coagulation Factors: Endogenous substances, usually proteins, that are involved in the blood coagulation process. [NIH]
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Blood Glucose: Glucose in blood. [NIH] Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blood Volume: Volume of circulating blood. It is the sum of the plasma volume and erythrocyte volume. [NIH] Body Fluids: Liquid components of living organisms. [NIH] Bolus: A single dose of drug usually injected into a blood vessel over a short period of time. Also called bolus infusion. [NIH] Bolus infusion: A single dose of drug usually injected into a blood vessel over a short period of time. Also called bolus. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] Brachytherapy: A collective term for interstitial, intracavity, and surface radiotherapy. It uses small sealed or partly-sealed sources that may be placed on or near the body surface or within a natural body cavity or implanted directly into the tissues. [NIH] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Brain Hypoxia: Lack of oxygen leading to unconsciousness. [NIH] Brain Infarction: The formation of an area of necrosis in the brain, including the cerebral hemispheres (cerebral infarction), thalami, basal ganglia, brain stem (brain stem infarctions), or cerebellum secondary to an insufficiency of arterial or venous blood flow. [NIH] Brain Ischemia: Localized reduction of blood flow to brain tissue due to arterial obtruction or systemic hypoperfusion. This frequently occurs in conjuction with brain hypoxia. Prolonged ischemia is associated with brain infarction. [NIH] Brain Neoplasms: Neoplasms of the intracranial components of the central nervous system, including the cerebral hemispheres, basal ganglia, hypothalamus, thalamus, brain stem, and cerebellum. Brain neoplasms are subdivided into primary (originating from brain tissue) and secondary (i.e., metastatic) forms. Primary neoplasms are subdivided into benign and malignant forms. In general, brain tumors may also be classified by age of onset, histologic type, or presenting location in the brain. [NIH]
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Brain Stem: The part of the brain that connects the cerebral hemispheres with the spinal cord. It consists of the mesencephalon, pons, and medulla oblongata. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]
Breakdown: A physical, metal, or nervous collapse. [NIH] Bronchi: The larger air passages of the lungs arising from the terminal bifurcation of the trachea. [NIH] Bronchial: Pertaining to one or more bronchi. [EU] Bronchitis: Inflammation (swelling and reddening) of the bronchi. [NIH] Bronchopulmonary: Pertaining to the lungs and their air passages; both bronchial and pulmonary. [EU] Buffers: A chemical system that functions to control the levels of specific ions in solution. When the level of hydrogen ion in solution is controlled the system is called a pH buffer. [NIH]
Bupivacaine: A widely used local anesthetic agent. [NIH] Burns: Injuries to tissues caused by contact with heat, steam, chemicals (burns, chemical), electricity (burns, electric), or the like. [NIH] Burns, Electric: Burns produced by contact with electric current or from a sudden discharge of electricity. [NIH] Caesarean section: A surgical incision through the abdominal and uterine walls in order to deliver a baby. [NIH] Caffeine: A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine's most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. It also relaxes smooth muscle, stimulates cardiac muscle, stimulates diuresis, and appears to be useful in the treatment of some types of headache. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide phosphodiesterases, antagonism of adenosine receptors, and modulation of intracellular calcium handling. [NIH] Calcification: Deposits of calcium in the tissues of the breast. Calcification in the breast can be seen on a mammogram, but cannot be detected by touch. There are two types of breast calcification, macrocalcification and microcalcification. Macrocalcifications are large deposits and are usually not related to cancer. Microcalcifications are specks of calcium that may be found in an area of rapidly dividing cells. Many microcalcifications clustered together may be a sign of cancer. [NIH] 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,
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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] Calcium Oxalate: The calcium salt of oxalic acid, occurring in the urine as crystals and in certain calculi. [NIH] Callus: A callosity or hard, thick skin; the bone-like reparative substance that is formed round the edges and fragments of broken bone. [NIH] Calmodulin: A heat-stable, low-molecular-weight activator protein found mainly in the brain and heart. The binding of calcium ions to this protein allows this protein to bind to cyclic nucleotide phosphodiesterases and to adenyl cyclase with subsequent activation. Thereby this protein modulates cyclic AMP and cyclic GMP levels. [NIH] Canonical: A particular nucleotide sequence in which each position represents the base more often found when many actual sequences of a given class of genetic elements are compared. [NIH] Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU] Capsaicin: Cytotoxic alkaloid from various species of Capsicum (pepper, paprika), of the Solanaceae. [NIH] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Carbamazepine: An anticonvulsant used to control grand mal and psychomotor or focal seizures. Its mode of action is not fully understood, but some of its actions resemble those of phenytoin; although there is little chemical resemblance between the two compounds, their three-dimensional structure is similar. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carbohydrate-Deficient Glycoprotein Syndrome: An inborn error of carbohydrate metabolism manifesting as a genetic multisystem disorder of autosomal recessive inheritance. A predominant feature is severe central and peripheral nervous system involvement resulting in psychomotor retardation, seizures, cerebellar ataxia, and other symptoms which include growth retardation, retinitis pigmentosa, hypothyroidism, and fatty liver. The notable biochemical feature is the deficiency of a large number of blood glycoproteins and decreased activities of various blood coagulation factors. [NIH] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] 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
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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] Cardiac arrest: A sudden stop of heart function. [NIH] Cardiac Output: The volume of blood passing through the heart per unit of time. It is usually expressed as liters (volume) per minute so as not to be confused with stroke volume (volume per beat). [NIH] Cardiopulmonary: Having to do with the heart and lungs. [NIH] Cardiotonic: 1. Having a tonic effect on the heart. 2. An agent that has a tonic effect on the heart. [EU] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] Cardiovascular System: The heart and the blood vessels by which blood is pumped and circulated through the body. [NIH] Carotene: The general name for a group of pigments found in green, yellow, and leafy vegetables, and yellow fruits. The pigments are fat-soluble, unsaturated aliphatic hydrocarbons functioning as provitamins and are converted to vitamin A through enzymatic processes in the intestinal wall. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Case series: A group or series of case reports involving patients who were given similar treatment. Reports of case series usually contain detailed information about the individual patients. This includes demographic information (for example, age, gender, ethnic origin) and information on diagnosis, treatment, response to treatment, and follow-up after treatment. [NIH] Caspase: Enzyme released by the cell at a crucial stage in apoptosis in order to shred all cellular proteins. [NIH] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [NIH] Catheters: A small, flexible tube that may be inserted into various parts of the body to inject or remove liquids. [NIH] Cations: Postively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis. [NIH] Caudal: Denoting a position more toward the cauda, or tail, than some specified point of reference; same as inferior, in human anatomy. [EU] Causal: Pertaining to a cause; directed against a cause. [EU] Cause of Death: Factors which produce cessation of all vital bodily functions. They can be analyzed from an epidemiologic viewpoint. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH]
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Cell Adhesion: Adherence of cells to surfaces or to other cells. [NIH] Cell Cycle: The complex series of phenomena, occurring between the end of one cell division and the end of the next, by which cellular material is divided between daughter cells. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Respiration: The metabolic process of all living cells (animal and plant) in which oxygen is used to provide a source of energy for the cell. [NIH] Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. [NIH] Cell Transplantation: Transference of cells within an individual, between individuals of the same species, or between individuals of different species. [NIH] Cellular metabolism: The sum of all chemical changes that take place in a cell through which energy and basic components are provided for essential processes, including the synthesis of new molecules and the breakdown and removal of others. [NIH] Cellulose: A polysaccharide with glucose units linked as in cellobiose. It is the chief constituent of plant fibers, cotton being the purest natural form of the substance. As a raw material, it forms the basis for many derivatives used in chromatography, ion exchange materials, explosives manufacturing, and pharmaceutical preparations. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Central Nervous System Infections: Pathogenic infections of the brain, spinal cord, and meninges. DNA virus infections; RNA virus infections; bacterial infections; mycoplasma infections; Spirochaetales infections; fungal infections; protozoan infections; helminthiasis; and prion diseases may involve the central nervous system as a primary or secondary process. [NIH] Cerebellar: Pertaining to the cerebellum. [EU] Cerebellar Diseases: Diseases that affect the structure or function of the cerebellum. Cardinal manifestations of cerebellar dysfunction include dysmetria, gait ataxia, and muscle hypotonia. [NIH] Cerebellum: Part of the metencephalon that lies in the posterior cranial fossa behind the brain stem. It is concerned with the coordination of movement. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral Arteries: The arteries supplying the cerebral cortex. [NIH] Cerebral Infarction: The formation of an area of necrosis in the cerebrum caused by an
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insufficiency of arterial or venous blood flow. Infarcts of the cerebrum are generally classified by hemisphere (i.e., left vs. right), lobe (e.g., frontal lobe infarction), arterial distribution (e.g., infarction, anterior cerebral artery), and etiology (e.g., embolic infarction). [NIH]
Cerebrospinal: Pertaining to the brain and spinal cord. [EU] Cerebrospinal fluid: CSF. The fluid flowing around the brain and spinal cord. Cerebrospinal fluid is produced in the ventricles in the brain. [NIH] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrovascular Disorders: A broad category of disorders characterized by impairment of blood flow in the arteries and veins which supply the brain. These include cerebral infarction; brain ischemia; hypoxia, brain; intracranial embolism and thrombosis; intracranial arteriovenous malformations; and vasculitis, central nervous system. In common usage, the term cerebrovascular disorders is not limited to conditions that affect the cerebrum, but refers to vascular disorders of the entire brain including the diencephalon; brain stem; and cerebellum. [NIH] 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] Chemoreceptor: A receptor adapted for excitation by chemical substances, e.g., olfactory and gustatory receptors, or a sense organ, as the carotid body or the aortic (supracardial) bodies, which is sensitive to chemical changes in the blood stream, especially reduced oxygen content, and reflexly increases both respiration and blood pressure. [EU] Chemotherapy: Treatment with anticancer drugs. [NIH] Chest Pain: Pressure, burning, or numbness in the chest. [NIH] Child Development: The continuous sequential physiological and psychological maturing of the child from birth up to but not including adolescence. It includes healthy responses to situations, but does not include growth in stature or size (= growth). [NIH] Chlorides: Inorganic compounds derived from hydrochloric acid that contain the Cl- ion. [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] Cholinergic: Resembling acetylcholine in pharmacological action; stimulated by or releasing acetylcholine or a related compound. [EU] Chorea: Involuntary, forcible, rapid, jerky movements that may be subtle or become confluent, markedly altering normal patterns of movement. Hypotonia and pendular reflexes are often associated. Conditions which feature recurrent or persistent episodes of chorea as a primary manifestation of disease are referred to as choreatic disorders. Chorea is also a frequent manifestation of basal ganglia diseases. [NIH] Chorioretinitis: Inflammation of the choroid in which the sensory retina becomes edematous and opaque. The inflammatory cells and exudate may burst through the sensory retina to cloud the vitreous body. [NIH] Choroid: The thin, highly vascular membrane covering most of the posterior of the eye
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between the retina and sclera. [NIH] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] 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 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] Circadian: Repeated more or less daily, i. e. on a 23- to 25-hour cycle. [NIH] Circulatory system: The system that contains the heart and the blood vessels and moves blood throughout the body. This system helps tissues get enough oxygen and nutrients, and it helps them get rid of waste products. The lymph system, which connects with the blood system, is often considered part of the circulatory system. [NIH] CIS: Cancer Information Service. The CIS is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER, or by using the Web site at http://cis.nci.nih.gov. [NIH] Clamp: A u-shaped steel rod used with a pin or wire for skeletal traction in the treatment of certain fractures. [NIH] Clarithromycin: A semisynthetic macrolide antibiotic derived from erythromycin that is active against a variety of microorganisms. It can inhibit protein synthesis in bacteria by reversibly binding to the 50S ribosomal subunits. This inhibits the translocation of aminoacyl transfer-RNA and prevents peptide chain elongation. [NIH] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]
Clinical study: A research study in which patients receive treatment in a clinic or other medical facility. Reports of clinical studies can contain results for single patients (case reports) or many patients (case series or clinical trials). [NIH] Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Clone: The term "clone" has acquired a new meaning. It is applied specifically to the bits of inserted foreign DNA in the hybrid molecules of the population. Each inserted segment originally resided in the DNA of a complex genome amid millions of other DNA segment. [NIH]
Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA
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molecules. [NIH] Coagulation: 1. The process of clot formation. 2. In colloid chemistry, the solidification of a sol into a gelatinous mass; an alteration of a disperse phase or of a dissolved solid which causes the separation of the system into a liquid phase and an insoluble mass called the clot or curd. Coagulation is usually irreversible. 3. In surgery, the disruption of tissue by physical means to form an amorphous residuum, as in electrocoagulation and photocoagulation. [EU] Coca: Any of several South American shrubs of the Erythroxylon genus (and family) that yield cocaine; the leaves are chewed with alum for CNS stimulation. [NIH] Cocaine: An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. [NIH] Cochlea: The part of the internal ear that is concerned with hearing. It forms the anterior part of the labyrinth, is conical, and is placed almost horizontally anterior to the vestibule. [NIH]
Coenzymes: Substances that are necessary for the action or enhancement of action of an enzyme. Many vitamins are coenzymes. [NIH] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Cognition: Intellectual or mental process whereby an organism becomes aware of or obtains knowledge. [NIH] Cognitive behavior therapy: A system of psychotherapy based on the premise that distorted or dysfunctional thinking, which influences a person's mood or behavior, is common to all psychosocial problems. The focus of therapy is to identify the distorted thinking and to replace it with more rational, adaptive thoughts and beliefs. [NIH] Colitis: Inflammation of the colon. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] 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] Colonic Neoplasms: Tumors or cancer of the colon. [NIH] Colony-Stimulating Factors: Glycoproteins found in a subfraction of normal mammalian plasma and urine. They stimulate the proliferation of bone marrow cells in agar cultures and the formation of colonies of granulocytes and/or macrophages. The factors include interleukin-3 (IL-3), granulocyte colony-stimulating factor (G-CSF), macrophage colonystimulating factor (M-CSF), and granulocyte-macrophage colony-stimulating factor (GMCSF). [NIH] Colorectal: Having to do with the colon or the rectum. [NIH]
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Colostrum: The thin, yellow, serous fluid secreted by the mammary glands during pregnancy and immediately postpartum before lactation begins. It consists of immunologically active substances, white blood cells, water, protein, fat, and carbohydrates. [NIH]
Comatose: Pertaining to or affected with coma. [EU] Combination Therapy: Association of 3 drugs to treat AIDS (AZT + DDC or DDI + protease inhibitor). [NIH] Common Bile Duct: The largest biliary duct. It is formed by the junction of the cystic duct and the hepatic duct. [NIH] Comorbidity: The presence of co-existing or additional diseases with reference to an initial diagnosis or with reference to the index condition that is the subject of study. Comorbidity may affect the ability of affected individuals to function and also their survival; it may be used as a prognostic indicator for length of hospital stay, cost factors, and outcome or survival. [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Compress: A plug used to occludate an orifice in the control of bleeding, or to mop up secretions; an absorbent pad. [NIH] Computational Biology: A field of biology concerned with the development of techniques
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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] Cone: One of the special retinal receptor elements which are presumed to be primarily concerned with perception of light and color stimuli when the eye is adapted to light. [NIH] Confusion: A mental state characterized by bewilderment, emotional disturbance, lack of clear thinking, and perceptual disorientation. [NIH] Congestion: Excessive or abnormal accumulation of blood in a part. [EU] Congestive heart failure: Weakness of the heart muscle that leads to a buildup of fluid in body tissues. [NIH] Conjunctiva: The mucous membrane that lines the inner surface of the eyelids and the anterior part of the sclera. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue Cells: A group of cells that includes fibroblasts, cartilage cells, adipocytes, smooth muscle cells, and bone cells. [NIH] Connexins: A group of homologous proteins which form the intermembrane channels of gap junctions. The connexins are the products of an identified gene family which has both highly conserved and highly divergent regions. The variety contributes to the wide range of functional properties of gap junctions. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH] Constipation: Infrequent or difficult evacuation of feces. [NIH] Constitutional: 1. Affecting the whole constitution of the body; not local. 2. Pertaining to the constitution. [EU] Constriction: The act of constricting. [NIH] Consumption: Pulmonary tuberculosis. [NIH] Contamination: The soiling or pollution by inferior material, as by the introduction of organisms into a wound, or sewage into a stream. [EU] 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] Controlled clinical trial: A clinical study that includes a comparison (control) group. The comparison group receives a placebo, another treatment, or no treatment at all. [NIH] Conventional therapy: A currently accepted and widely used treatment for a certain type of disease, based on the results of past research. Also called conventional treatment. [NIH]
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Conventional treatment: A currently accepted and widely used treatment for a certain type of disease, based on the results of past research. Also called conventional therapy. [NIH] Convulsion: A violent involuntary contraction or series of contractions of the voluntary muscles. [EU] Convulsive: Relating or referring to spasm; affected with spasm; characterized by a spasm or spasms. [NIH] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or 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 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] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Corticosteroid: Any of the steroids elaborated by the adrenal cortex (excluding the sex hormones of adrenal origin) in response to the release of corticotrophin (adrenocorticotropic hormone) by the pituitary gland, to any of the synthetic equivalents of these steroids, or to angiotensin II. They are divided, according to their predominant biological activity, into three major groups: glucocorticoids, chiefly influencing carbohydrate, fat, and protein metabolism; mineralocorticoids, affecting the regulation of electrolyte and water balance; and C19 androgens. Some corticosteroids exhibit both types of activity in varying degrees, and others exert only one type of effect. The corticosteroids are used clinically for hormonal replacement therapy, for suppression of ACTH secretion by the anterior pituitary, as antineoplastic, antiallergic, and anti-inflammatory agents, and to suppress the immune response. Called also adrenocortical hormone and corticoid. [EU] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to stress. [NIH] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Craniocerebral Trauma: Traumatic injuries involving the cranium and intracranial structures (i.e., brain; cranial nerves; meninges; and other structures). Injuries may be classified by whether or not the skull is penetrated (i.e., penetrating vs. nonpenetrating) or whether there is an associated hemorrhage. [NIH] Creatinine: A compound that is excreted from the body in urine. Creatinine levels are measured to monitor kidney function. [NIH] Critical Care: Health care provided to a critically ill patient during a medical emergency or crisis. [NIH] Cross-Sectional Studies: Studies in which the presence or absence of disease or other health-related variables are determined in each member of the study population or in a representative sample at one particular time. This contrasts with longitudinal studies which
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are followed over a period of time. [NIH] Cryostat: A batchwise operating apparatus in which a cryogenic liquid or solid is used to maintain by evaporation a cryotemperature which needs not be constant but may vary in a predetermined fashion. [NIH] Cues: Signals for an action; that specific portion of a perceptual field or pattern of stimuli to which a subject has learned to respond. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Having to do with the skin. [NIH] Cyanide: An extremely toxic class of compounds that can be lethal on inhaling of ingesting in minute quantities. [NIH] Cyanosis: A bluish or purplish discoloration of the skin and mucous membranes due to an increase in the amount of deoxygenated hemoglobin in the blood or a structural defect in the hemoglobin molecule. [NIH] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] Cyclin: Molecule that regulates the cell cycle. [NIH] Cysteine: A thiol-containing non-essential amino acid that is oxidized to form cystine. [NIH] Cystine: A covalently linked dimeric nonessential amino acid formed by the oxidation of cysteine. Two molecules of cysteine are joined together by a disulfide bridge to form cystine. [NIH]
Cystitis: Inflammation of the urinary bladder. [EU] Cytogenetics: A branch of genetics which deals with the cytological and molecular behavior of genes and chromosomes during cell division. [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] Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. [NIH] Cytotoxic: Cell-killing. [NIH] Data Collection: Systematic gathering of data for a particular purpose from various sources, including questionnaires, interviews, observation, existing records, and electronic devices. The process is usually preliminary to statistical analysis of the data. [NIH] Databases, Bibliographic: Extensive collections, reputedly complete, of references and citations to books, articles, publications, etc., generally on a single subject or specialized subject area. Databases can operate through automated files, libraries, or computer disks. The concept should be differentiated from factual databases which is used for collections of data and facts apart from bibliographic references to them. [NIH] Day Care: Institutional health care of patients during the day. The patients return home at night. [NIH] Deamination: The removal of an amino group (NH2) from a chemical compound. [NIH] Decarboxylation: The removal of a carboxyl group, usually in the form of carbon dioxide, from a chemical compound. [NIH] Decidua: The epithelial lining of the endometrium that is formed before the fertilized ovum
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reaches the uterus. The fertilized ovum embeds in the decidua. If the ovum is not fertilized, the decidua is shed during menstruation. [NIH] Decision Making: The process of making a selective intellectual judgment when presented with several complex alternatives consisting of several variables, and usually defining a course of action or an idea. [NIH] Decompensation: Failure of compensation; cardiac decompensation is marked by dyspnea, venous engorgement, and edema. [EU] Decubitus: An act of lying down; also the position assumed in lying down. [EU] Decubitus Ulcer: An ulceration caused by prolonged pressure in patients permitted to lie too still for a long period of time. The bony prominences of the body are the most frequently affected sites. The ulcer is caused by ischemia of the underlying structures of the skin, fat, and muscles as a result of the sustained and constant pressure. [NIH] Defense Mechanisms: Unconscious process used by an individual or a group of individuals in order to cope with impulses, feelings or ideas which are not acceptable at their conscious level; various types include reaction formation, projection and self reversal. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Dehydration: The condition that results from excessive loss of body water. [NIH] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Delirium: (DSM III-R) an acute, reversible organic mental disorder characterized by reduced ability to maintain attention to external stimuli and disorganized thinking as manifested by rambling, irrelevant, or incoherent speech; there are also a reduced level of consciousness, sensory misperceptions, disturbance of the sleep-wakefulness cycle and level of psychomotor activity, disorientation to time, place, or person, and memory impairment. Delirium may be caused by a large number of conditions resulting in derangement of cerebral metabolism, including systemic infection, poisoning, drug intoxication or withdrawal, seizures or head trauma, and metabolic disturbances such as hypoxia, hypoglycaemia, fluid, electrolyte, or acid-base imbalances, or hepatic or renal failure. Called also acute confusional state and acute brain syndrome. [EU] Delusions: A false belief regarding the self or persons or objects outside the self that persists despite the facts, and is not considered tenable by one's associates. [NIH] Dementia: An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness. [NIH] Denaturation: Rupture of the hydrogen bonds by heating a DNA solution and then cooling it rapidly causes the two complementary strands to separate. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Dendritic: 1. Branched like a tree. 2. Pertaining to or possessing dendrites. [EU] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Dental Care: The total of dental diagnostic, preventive, and restorative services provided to meet the needs of a patient (from Illustrated Dictionary of Dentistry, 1982). [NIH] Dentate Gyrus: Gray matter situated above the gyrus hippocampi. It is composed of three
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layers. The molecular layer is continuous with the hippocampus in the hippocampal fissure. The granular layer consists of closely arranged spherical or oval neurons, called granule cells, whose axons pass through the polymorphic layer ending on the dendrites of pyramidal cells in the hippocampus. [NIH] Depolarization: The process or act of neutralizing polarity. In neurophysiology, the reversal of the resting potential in excitable cell membranes when stimulated, i.e., the tendency of the cell membrane potential to become positive with respect to the potential outside the cell. [EU] Depressive Disorder: An affective disorder manifested by either a dysphoric mood or loss of interest or pleasure in usual activities. The mood disturbance is prominent and relatively persistent. [NIH] Deprivation: Loss or absence of parts, organs, powers, or things that are needed. [EU] Detergents: Purifying or cleansing agents, usually salts of long-chain aliphatic bases or acids, that exert cleansing (oil-dissolving) and antimicrobial effects through a surface action that depends on possessing both hydrophilic and hydrophobic properties. [NIH] Detoxification: Treatment designed to free an addict from his drug habit. [EU] 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] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diabetes, Gestational: Either symptomatic diabetes or impaired glucose tolerance induced by pregnancy but resolved at the end of pregnancy. It does not include previously diagnosed diabetics who become pregnant (pregnancy in diabetics). [NIH] Diabetic Foot: Ulcers of the foot as a complication of diabetes. Diabetic foot, often with infection, is a common serious complication of diabetes and may require hospitalization and disfiguring surgery. The foot ulcers are probably secondary to neuropathies and vascular problems. [NIH] Diabetic Ketoacidosis: Complication of diabetes resulting from severe insulin deficiency coupled with an absolute or relative increase in glucagon concentration. The metabolic acidosis is caused by the breakdown of adipose stores and resulting increased levels of free fatty acids. Glucagon accelerates the oxidation of the free fatty acids producing excess ketone bodies (ketosis). [NIH] Diabetic Retinopathy: Retinopathy associated with diabetes mellitus, which may be of the background type, progressively characterized by microaneurysms, interretinal punctuate macular edema, or of the proliferative type, characterized by neovascularization of the retina and optic disk, which may project into the vitreous, proliferation of fibrous tissue, vitreous hemorrhage, and retinal detachment. [NIH] Diagnostic 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] Diaphoresis: Perspiration, especially profuse perspiration. Called also sudoresis. [EU] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Diastolic: Of or pertaining to the diastole. [EU] Diencephalon: The paired caudal parts of the prosencephalon from which the thalamus, hypothalamus, epithalamus, and subthalamus are derived. [NIH]
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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] Dietitian: An expert in nutrition who helps people plan what and how much food to eat. [NIH]
Diffusion: The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space; a major mechanism of biological transport. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive system: The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] Digestive tract: The organs through which food passes when food is eaten. These organs are the mouth, esophagus, stomach, small and large intestines, and rectum. [NIH] Digitalis: A genus of toxic herbaceous Eurasian plants of the Scrophulaceae which yield cardiotonic glycosides. The most useful are Digitalis lanata and D. purpurea. [NIH] Dilatation: The act of dilating. [NIH] Dilation: A process by which the pupil is temporarily enlarged with special eye drops (mydriatic); allows the eye care specialist to better view the inside of the eye. [NIH] Diploid: Having two sets of chromosomes. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Discrimination: The act of qualitative and/or quantitative differentiation between two or more stimuli. [NIH] Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [EU] Dislocation: The displacement of any part, more especially of a bone. Called also luxation. [EU]
Disorientation: The loss of proper bearings, or a state of mental confusion as to time, place, or identity. [EU] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Diuresis: Increased excretion of urine. [EU] Diuretic: A drug that increases the production of urine. [NIH] Diuretics, Thiazide: Diuretics characterized as analogs of 1,2,4-benzothiadiazine-1,1dioxide. All have a common mechanism of action and differ primarily in the dose required
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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] Diurnal: Occurring during the day. [EU] Dizziness: An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. [NIH] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] Dorsal: 1. Pertaining to the back or to any dorsum. 2. Denoting a position more toward the back surface than some other object of reference; same as posterior in human anatomy; superior in the anatomy of quadrupeds. [EU] Dosage schedule: A scheme set up to determine and regulate size, frequency and number of doses. [EU] 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 Monitoring: The process of observing, recording, or detecting the effects of a chemical substance administered to an individual therapeutically or diagnostically. [NIH] Drug Resistance: Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from drug tolerance which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration. [NIH] 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] Ductus Arteriosus: A fetal blood vessel connecting the pulmonary artery with the descending aorta. [NIH] Dumping Syndrome: Gastrointestinal nonfunctioning pylorus. [NIH]
symptoms
resulting
from
an
absent
or
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] Dyskinesia: Impairment of the power of voluntary movement, resulting in fragmentary or incomplete movements. [EU] Dyslipidemia: Disorders in the lipoprotein metabolism; classified as hypercholesterolemia, hypertriglyceridemia, combined hyperlipidemia, and low levels of high-density lipoprotein
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(HDL) cholesterol. All of the dyslipidemias can be primary or secondary. Both elevated levels of low-density lipoprotein (LDL) cholesterol and low levels of HDL cholesterol predispose to premature atherosclerosis. [NIH] Dyspepsia: Impaired digestion, especially after eating. [NIH] Dysphoric: A feeling of unpleasantness and discomfort. [NIH] Dysplasia: Cells that look abnormal under a microscope but are not cancer. [NIH] Dyspnea: Difficult or labored breathing. [NIH] Dystonia: Disordered tonicity of muscle. [EU] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] Eating Disorders: A group of disorders characterized by physiological and psychological disturbances in appetite or food intake. [NIH] Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Effector cell: A cell that performs a specific function in response to a stimulus; usually used to describe cells in the immune system. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Elasticity: Resistance and recovery from distortion of shape. [NIH] Elastin: The protein that gives flexibility to tissues. [NIH] Elective: Subject to the choice or decision of the patient or physician; applied to procedures that are advantageous to the patient but not urgent. [EU] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] Electrophoresis: An electrochemical process in which macromolecules or colloidal particles with a net electric charge migrate in a solution under the influence of an electric current. [NIH]
Electrophysiological: Pertaining to electrophysiology, that is a branch of physiology that is concerned with the electric phenomena associated with living bodies and involved in their functional activity. [EU] Elementary Particles: Individual components of atoms, usually subatomic; subnuclear particles are usually detected only when the atomic nucleus decays and then only transiently, as most of them are unstable, often yielding pure energy without substance, i.e., radiation. [NIH] Emaciation: Clinical manifestation of excessive leanness usually caused by disease or a lack of nutrition. [NIH] Emboli: Bit of foreign matter which enters the blood stream at one point and is carried until
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it is lodged or impacted in an artery and obstructs it. It may be a blood clot, an air bubble, fat or other tissue, or clumps of bacteria. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Embryo Transfer: Removal of a mammalian embryo from one environment and replacement in the same or a new environment. The embryo is usually in the pre-nidation phase, i.e., a blastocyst. The process includes embryo or blastocyst transplantation or transfer after in vitro fertilization and transfer of the inner cell mass of the blastocyst. It is not used for transfer of differentiated embryonic tissue, e.g., germ layer cells. [NIH] Embryogenesis: The process of embryo or embryoid formation, whether by sexual (zygotic) or asexual means. In asexual embryogenesis embryoids arise directly from the explant or on intermediary callus tissue. In some cases they arise from individual cells (somatic cell embryoge). [NIH] Emergency Medicine: A branch of medicine concerned with an individual's resuscitation, transportation and care from the point of injury or beginning of illness through the hospital or other emergency treatment facility. [NIH] Emergency Treatment: First aid or other immediate intervention for accidents or medical conditions requiring immediate care and treatment before definitive medical and surgical management can be procured. [NIH] Emesis: Vomiting; an act of vomiting. Also used as a word termination, as in haematemesis. [EU]
Emollient: Softening or soothing; called also malactic. [EU] Emphysema: A pathological accumulation of air in tissues or organs. [NIH] Empirical: A treatment based on an assumed diagnosis, prior to receiving confirmatory laboratory test results. [NIH] 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 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] Endometrium: The layer of tissue that lines the uterus. [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-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
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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] Enhancer: Transcriptional element in the virus genome. [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] Enteritis: Inflammation of the intestine, applied chiefly to inflammation of the small intestine; see also enterocolitis. [EU] Enterocolitis: Inflammation of the intestinal mucosa of the small and large bowel. [NIH] Entorhinal Cortex: Cortex where the signals are combined with those from other sensory systems. [NIH] Environmental Exposure: The exposure to potentially harmful chemical, physical, or biological agents in the environment or to environmental factors that may include ionizing radiation, pathogenic organisms, or toxic chemicals. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]
Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Eosinophils: Granular leukocytes with a nucleus that usually has two lobes connected by a slender thread of chromatin, and cytoplasm containing coarse, round granules that are uniform in size and stainable by eosin. [NIH] Ependyma: A thin membrane that lines the ventricles of the brain and the central canal of the spinal cord. [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] Epigastric: Having to do with the upper middle area of the abdomen. [NIH] Epilepticus: Repeated and prolonged epileptic seizures without recovery of consciousness between attacks. [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] Equipment and Supplies: Expendable and nonexpendable equipment, supplies, apparatus, and instruments that are used in diagnostic, surgical, therapeutic, scientific, and experimental procedures. [NIH] Erectile: The inability to get or maintain an erection for satisfactory sexual intercourse. Also
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called impotence. [NIH] Erection: The condition of being made rigid and elevated; as erectile tissue when filled with blood. [EU] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Erythromycin: A bacteriostatic antibiotic substance produced by Streptomyces erythreus. Erythromycin A is considered its major active component. In sensitive organisms, it inhibits protein synthesis by binding to 50S ribosomal subunits. This binding process inhibits peptidyl transferase activity and interferes with translocation of amino acids during translation and assembly of proteins. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]
Essential Tremor: A rhythmic, involuntary, purposeless, oscillating movement resulting from the alternate contraction and relaxation of opposing groups of muscles. [NIH] Estrogen: One of the two female sex hormones. [NIH] Ethanol: A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. [NIH] Ether: One of a class of organic compounds in which any two organic radicals are attached directly to a single oxygen atom. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Evacuation: An emptying, as of the bowels. [EU] Evoke: The electric response recorded from the cerebral cortex after stimulation of a peripheral sense organ. [NIH] Excipients: Usually inert substances added to a prescription in order to provide suitable consistency to the dosage form; a binder, matrix, base or diluent in pills, tablets, creams, salves, etc. [NIH] Excitability: Property of a cardiac cell whereby, when the cell is depolarized to a critical level (called threshold), the membrane becomes permeable and a regenerative inward current causes an action potential. [NIH] Excitation: An act of irritation or stimulation or of responding to a stimulus; the addition of energy, as the excitation of a molecule by absorption of photons. [EU] Excitatory: When cortical neurons are excited, their output increases and each new input they receive while they are still excited raises their output markedly. [NIH] Excitatory Amino Acid Agonists: Drugs that bind to and activate excitatory amino acid receptors. [NIH] Excitatory Amino Acid Antagonists: Drugs that bind to but do not activate excitatory amino acid receptors, thereby blocking the actions of agonists. [NIH] Excitatory Amino Acids: Endogenous amino acids released by neurons as excitatory neurotransmitters. Glutamic acid is the most common excitatory neurotransmitter in the brain. Aspartic acid has been regarded as an excitatory transmitter for many years, but the extent of its role as a transmitter is unclear. [NIH] Excitotoxicity: Excessive exposure to glutamate or related compounds can kill brain neurons, presumably by overstimulating them. [NIH]
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Excrete: To get rid of waste from the body. [NIH] Exercise Test: Controlled physical activity, more strenuous than at rest, which is performed in order to allow assessment of physiological functions, particularly cardiovascular and pulmonary, but also aerobic capacity. Maximal (most intense) exercise is usually required but submaximal exercise is also used. The intensity of exercise is often graded, using criteria such as rate of work done, oxygen consumption, and heart rate. Physiological data obtained from an exercise test may be used for diagnosis, prognosis, and evaluation of disease severity, and to evaluate therapy. Data may also be used in prescribing exercise by determining a person's exercise capacity. [NIH] Exhaustion: The feeling of weariness of mind and body. [NIH] Exocrine: Secreting outwardly, via a duct. [EU] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Expert Systems: Computer programs based on knowledge developed from consultation with experts on a problem, and the processing and/or formalizing of this knowledge using these programs in such a manner that the problems may be solved. [NIH] Expiration: The act of breathing out, or expelling air from the lungs. [EU] External-beam radiation: Radiation therapy that uses a machine to aim high-energy rays at the cancer. Also called external radiation. [NIH] Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extracellular Matrix Proteins: Macromolecular organic compounds that contain carbon, hydrogen, oxygen, nitrogen, and usually, sulfur. These macromolecules (proteins) form an intricate meshwork in which cells are embedded to construct tissues. Variations in the relative types of macromolecules and their organization determine the type of extracellular matrix, each adapted to the functional requirements of the tissue. The two main classes of macromolecules that form the extracellular matrix are: glycosaminoglycans, usually linked to proteins (proteoglycans), and fibrous proteins (e.g., collagen, elastin, fibronectins and laminin). [NIH] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] Extrapyramidal: Outside of the pyramidal tracts. [EU] Extremity: A limb; an arm or leg (membrum); sometimes applied specifically to a hand or foot. [EU] Failure to Thrive: A condition in which an infant or child's weight gain and growth are far below usual levels for age. [NIH] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]
Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH]
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Fatty Liver: The buildup of fat in liver cells. The most common cause is alcoholism. Other causes include obesity, diabetes, and pregnancy. Also called steatosis. [NIH] Feces: The excrement discharged from the intestines, consisting of bacteria, cells exfoliated from the intestines, secretions, chiefly of the liver, and a small amount of food residue. [EU] Fertilization in Vitro: Fertilization of an egg outside the body when the egg is normally fertilized in the body. [NIH] Fetal Blood: Blood of the fetus. Exchange of nutrients and waste between the fetal and maternal blood occurs via the placenta. The cord blood is blood contained in the umbilical vessels at the time of delivery. [NIH] Fetal Death: Death of the young developing in utero. [NIH] Fetal Monitoring: Physiologic or biochemical monitoring of the fetus. It is usually done during labor and may be performed in conjunction with the monitoring of uterine activity. It may also be performed prenatally as when the mother is undergoing surgery. [NIH] Fetoprotein: Transabdominal aspiration of fluid from the amniotic sac with a view to detecting increases of alpha-fetoprotein in maternal blood during pregnancy, as this is an important indicator of open neural tube defects in the fetus. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibrin: A protein derived from fibrinogen in the presence of thrombin, which forms part of the blood clot. [NIH] Fibrinogen: Plasma glycoprotein clotted by thrombin, composed of a dimer of three nonidentical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products. [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibronectins: Glycoproteins found on the surfaces of cells, particularly in fibrillar structures. The proteins are lost or reduced when these cells undergo viral or chemical transformation. They are highly susceptible to proteolysis and are substrates for activated blood coagulation factor VIII. The forms present in plasma are called cold-insoluble globulins. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Fistula: Abnormal communication most commonly seen between two internal organs, or between an internal organ and the surface of the body. [NIH] Flatus: Gas passed through the rectum. [NIH] 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] Fluorescence: The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis. [NIH] 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
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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 Exchange: See: Exchange lists. [NIH] Food Habits: Acquired or learned food preferences. [NIH] Food Hypersensitivity: Gastrointestinal disturbances, skin eruptions, or shock due to allergic reactions to allergens ingested in food. [NIH] Food Labeling: Use of written, printed, or graphic materials upon or accompanying a food or its container or wrapper. The concept includes ingredients, nutritional value, directions, warnings, and other relevant information. [NIH] Food Preferences: The selection of one food over another. [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] Fractionation: Dividing the total dose of radiation therapy into several smaller, equal doses delivered over a period of several days. [NIH] Frontal Lobe: The anterior part of the cerebral hemisphere. [NIH] Frozen Sections: Thinly cut sections of frozen tissue specimens prepared with a cryostat or freezing microtome. [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: A type of sugar found in many fruits and vegetables and in honey. Fructose is used to sweeten some diet foods. It is considered a nutritive sweetener because it has calories. [NIH] Functional magnetic resonance imaging: A noninvasive tool used to observe functioning in the brain or other organs by detecting changes in chemical composition, blood flow, or both. [NIH]
Fuzzy Logic: Approximate, quantitative reasoning that is concerned with the linguistic ambiguity which exists in natural or synthetic language. At its core are variables such as good, bad, and young as well as modifiers such as more, less, and very. These ordinary terms represent fuzzy sets in a particular problem. Fuzzy logic plays a key role in many medical expert systems. [NIH]
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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] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Ganglionic Blockers: Agents having as their major action the interruption of neural transmission at nicotinic receptors on postganglionic autonomic neurons. Because their actions are so broad, including blocking of sympathetic and parasympathetic systems, their therapeutic use has been largely supplanted by more specific drugs. They may still be used in the control of blood pressure in patients with acute dissecting aortic aneurysm and for the induction of hypotension in surgery. [NIH] Gangrene: Death and putrefaction of tissue usually due to a loss of blood supply. [NIH] Gap Junctions: Connections between cells which allow passage of small molecules and electric current. Gap junctions were first described anatomically as regions of close apposition between cells with a narrow (1-2 nm) gap between cell membranes. The variety in the properties of gap junctions is reflected in the number of connexins, the family of proteins which form the junctions. [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 Emptying: The evacuation of food from the stomach into the duodenum. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]
Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gastroparesis: Nerve or muscle damage in the stomach. Causes slow digestion and emptying, vomiting, nausea, or bloating. Also called delayed gastric emptying. [NIH] Gastrostomy: Creation of an artificial external opening into the stomach for nutritional support or gastrointestinal compression. [NIH] Gavage: Feeding by a tube passed into the stomach; called also tube feeding. [NIH] Gelatin: A product formed from skin, white connective tissue, or bone collagen. It is used as a protein food adjuvant, plasma substitute, hemostatic, suspending agent in pharmaceutical preparations, and in the manufacturing of capsules and suppositories. [NIH] Gels: Colloids with a solid continuous phase and liquid as the dispersed phase; gels may be unstable when, due to temperature or other cause, the solid phase liquifies; the resulting colloid is called a sol. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]
Gene Deletion: A genetic rearrangement through loss of segments of DNA or RNA, bringing sequences which are normally separated into close proximity. This deletion may be detected using cytogenetic techniques and can also be inferred from the phenotype, indicating a deletion at one specific locus. [NIH] Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH]
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General practitioner: A medical practitioner who does not specialize in a particular branch of medicine or limit his practice to a specific class of diseases. [NIH] Genetic Code: The specifications for how information, stored in nucleic acid sequence (base sequence), is translated into protein sequence (amino acid sequence). The start, stop, and order of amino acids of a protein is specified by consecutive triplets of nucleotides called codons (codon). [NIH] Genetic Counseling: Advising families of the risks involved pertaining to birth defects, in order that they may make an informed decision on current or future pregnancies. [NIH] Genetic Engineering: Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc. [NIH] Genetic testing: Analyzing DNA to look for a genetic alteration that may indicate an increased risk for developing a specific disease or disorder. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genital: Pertaining to the genitalia. [EU] Genomics: The systematic study of the complete DNA sequences (genome) of organisms. [NIH]
Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Geriatric: Pertaining to the treatment of the aged. [EU] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] Gestational: Psychosis attributable to or occurring during pregnancy. [NIH] Gestational Age: Age of the conceptus. In humans, this may be assessed by medical history, physical examination, early immunologic pregnancy tests, radiography, ultrasonography, and amniotic fluid analysis. [NIH] Ginseng: An araliaceous genus of plants that contains a number of pharmacologically active agents used as stimulants, sedatives, and tonics, especially in traditional medicine. [NIH] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Gliosis: The production of a dense fibrous network of neuroglia; includes astrocytosis, which is a proliferation of astrocytes in the area of a degenerative lesion. [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]
Glossitis: Inflammation of the tongue. [NIH] Glucagonoma: Glucagon-secreting tumor of the pancreatic alpha cells characterized by a distinctive rash, weight loss, stomatitis, glossitis, diabetes, hypoaminoacidemia, and normochromic normocytic anemia. [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]
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Glucokinase: A group of enzymes that catalyzes the conversion of ATP and D-glucose to ADP and D-glucose 6-phosphate. They are found in invertebrates and microorganisms and are highly specific for glucose. (Enzyme Nomenclature, 1992) EC 2.7.1.2. [NIH] 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 Clamp Technique: Maintenance of a constant blood glucose level by perfusion or infusion with glucose or insulin. It is used for the study of metabolic rates (e.g., in glucose, lipid, amino acid metabolism) at constant glucose concentration. [NIH] Glucose Intolerance: A pathological state in which the fasting plasma glucose level is less than 140 mg per deciliter and the 30-, 60-, or 90-minute plasma glucose concentration following a glucose tolerance test exceeds 200 mg per deciliter. This condition is seen frequently in diabetes mellitus but also occurs with other diseases. [NIH] Glucose tolerance: The power of the normal liver to absorb and store large quantities of glucose and the effectiveness of intestinal absorption of glucose. The glucose tolerance test is a metabolic test of carbohydrate tolerance that measures active insulin, a hepatic function based on the ability of the liver to absorb glucose. The test consists of ingesting 100 grams of glucose into a fasting stomach; blood sugar should return to normal in 2 to 21 hours after ingestion. [NIH] Glucose Tolerance Test: Determination of whole blood or plasma sugar in a fasting state before and at prescribed intervals (usually 1/2 hr, 1 hr, 3 hr, 4 hr) after taking a specified amount (usually 100 gm orally) of glucose. [NIH] Glutamate: Excitatory neurotransmitter of the brain. [NIH] Glutamate Dehydrogenase: An enzyme that catalyzes the conversion of L-glutamate and water to 2-oxoglutarate and NH3 in the presence of NAD+. (From Enzyme Nomenclature, 1992) EC 1.4.1.2. [NIH] Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid (glutamate) is the most common excitatory neurotransmitter in the central nervous system. [NIH]
Glutamine: A non-essential amino acid present abundantly throught the body and is involved in many metabolic processes. It is synthesized from glutamic acid and ammonia. It is the principal carrier of nitrogen in the body and is an important energy source for many cells. [NIH] Glyburide: An antidiabetic sulfonylurea derivative with actions similar to those of chlorpropamide. [NIH] Glycerol: A trihydroxy sugar alcohol that is an intermediate in carbohydrate and lipid metabolism. It is used as a solvent, emollient, pharmaceutical agent, and sweetening agent. [NIH]
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,
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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] Glycoprotein: A protein that has sugar molecules attached to it. [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] Glycoside: Any compound that contains a carbohydrate molecule (sugar), particularly any such natural product in plants, convertible, by hydrolytic cleavage, into sugar and a nonsugar component (aglycone), and named specifically for the sugar contained, as glucoside (glucose), pentoside (pentose), fructoside (fructose) etc. [EU] Gonadal: Pertaining to a gonad. [EU] Gonads: The gamete-producing glands, ovary or testis. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Gp120: 120-kD HIV envelope glycoprotein which is involved in the binding of the virus to its membrane receptor, the CD4 molecule, found on the surface of certain cells in the body. [NIH]
Grade: The grade of a tumor depends on how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread. Grading systems are different for each type of cancer. [NIH] Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Graft Rejection: An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient. [NIH] Grafting: The operation of transfer of tissue from one site to another. [NIH] Gramicidin: Antibiotic mixture that is one of the two principle components of tyrothricin from Bacillus brevis. Gramicidin C or S is a cyclic, ten-amino acid polypeptide and gramicidins A, B, D, etc., seem to be linear polypeptides. The mixture is used topically for gram-positive organisms. It is toxic to blood, liver, kidneys, meninges, and the olfactory apparatus. [NIH] Gram-positive: Retaining the stain or resisting decolorization by alcohol in Gram's method of staining, a primary characteristic of bacteria whose cell wall is composed of a thick layer of peptidologlycan with attached teichoic acids. [EU] Granulocyte Colony-Stimulating Factor: A glycoprotein of MW 25 kDa containing internal disulfide bonds. It induces the survival, proliferation, and differentiation of neutrophilic granulocyte precursor cells and functionally activates mature blood neutrophils. Among the family of colony-stimulating factors, G-CSF is the most potent inducer of terminal differentiation to granulocytes and macrophages of leukemic myeloid cell lines. [NIH] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Growth: The progressive development of a living being or part of an organism from its
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earliest stage to maturity. [NIH] Growth factors: Substances made by the body that function to regulate cell division and cell survival. Some growth factors are also produced in the laboratory and used in biological therapy. [NIH] Guanidine: A strong organic base existing primarily as guanidium ions at physiological pH. It is found in the urine as a normal product of protein metabolism. It is also used in laboratory research as a protein denaturant. (From Martindale, the Extra Pharmacopoeia, 30th ed and Merck Index, 12th ed) It is also used in the treatment of myasthenia and as a fluorescent probe in HPLC. [NIH] Guanylate Cyclase: An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2. [NIH] Habitual: Of the nature of a habit; according to habit; established by or repeated by force of habit, customary. [EU] Haematemesis: The vomiting of blood. [EU] Hallucinogen: A hallucination-producing drug, a category of drugs producing this effect. The user of a hallucinogenic drug is almost invariably aware that what he is seeing are hallucinations. [NIH] Haploid: An organism with one basic chromosome set, symbolized by n; the normal condition of gametes in diploids. [NIH] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH] Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Headache Disorders: Common conditions characterized by persistent or recurrent headaches. Headache syndrome classification systems may be based on etiology (e.g., vascular headache, post-traumatic headaches, etc.), temporal pattern (e.g., cluster headache, paroxysmal hemicrania, etc.), and precipitating factors (e.g., cough headache). [NIH] 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] Heartbeat: One complete contraction of the heart. [NIH] Heartburn: Substernal pain or burning sensation, usually associated with regurgitation of gastric juice into the esophagus. [NIH] Hemangiopericytoma: A type of cancer involving blood vessels and soft tissue. [NIH] Hematoma: An extravasation of blood localized in an organ, space, or tissue. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemiparesis: The weakness or paralysis affecting one side of the body. [NIH]
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Hemochromatosis: A disease that occurs when the body absorbs too much iron. The body stores the excess iron in the liver, pancreas, and other organs. May cause cirrhosis of the liver. Also called iron overload disease. [NIH] Hemodialysis: The use of a machine to clean wastes from the blood after the kidneys have failed. The blood travels through tubes to a dialyzer, which removes wastes and extra fluid. The cleaned blood then flows through another set of tubes back into the body. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] Hemoglobin A: Normal adult human hemoglobin. The globin moiety consists of two alpha and two beta chains. [NIH] Hemoglobin M: A group of abnormal hemoglobins in which amino acid substitutions take place in either the alpha or beta chains but near the heme iron. This results in facilitated oxidation of the hemoglobin to yield excess methemoglobin which leads to cyanosis. [NIH] Hemoglobinuria: The presence of free hemoglobin in the urine. [NIH] Hemolytic: A disease that affects the blood and blood vessels. It destroys red blood cells, cells that cause the blood to clot, and the lining of blood vessels. HUS is often caused by the Escherichia coli bacterium in contaminated food. People with HUS may develop acute renal failure. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemorrhagic stroke: A disorder involving bleeding within ischemic brain tissue. Hemorrhagic stroke occurs when blood vessels that are damaged or dead from lack of blood supply (infarcted), located within an area of infarcted brain tissue, rupture and transform an "ischemic" stroke into a hemorrhagic stroke. Ischemia is inadequate tissue oxygenation caused by reduced blood flow; infarction is tissue death resulting from ischemia. Bleeding irritates the brain tissues, causing swelling (cerebral edema). Blood collects into a mass (hematoma). Both swelling and hematoma will compress and displace brain tissue. [NIH] Hemostasis: The process which spontaneously arrests the flow of blood from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation. [NIH]
Hepatic: Refers to the liver. [NIH] Hepatic Encephalopathy: A condition that may cause loss of consciousness and coma. It is usually the result of advanced liver disease. Also called hepatic coma. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatitis A: Hepatitis caused by hepatovirus. It can be transmitted through fecal contamination of food or water. [NIH] Hepatitis, Alcoholic: An acute or chronic degenerative and inflammatory lesion of the liver in the alcoholic which is potentially progressive though sometimes reversible. It does not necessarily include steatosis, fibrosis, or cirrhosis of alcoholics, although it is frequently
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associated with these conditions. It is characterized by liver cell necrosis, infiltration by polymorphonuclear leukocytes and lymphocytes, and Mallory bodies. The morphologic changes of chronic alcoholic hepatitis are not likely to be confused with chronic hepatitis. [NIH]
Hepatoblastoma: A type of liver tumor that occurs in infants and children. [NIH] Hepatocyte: A liver cell. [NIH] Hepatotoxic: Toxic to liver cells. [EU] 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] Heterodimers: Zippered pair of nonidentical proteins. [NIH] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]
Hippocampus: A curved elevation of gray matter extending the entire length of the floor of the temporal horn of the lateral ventricle (Dorland, 28th ed). The hippocampus, subiculum, and dentate gyrus constitute the hippocampal formation. Sometimes authors include the entorhinal cortex in the hippocampal formation. [NIH] 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]
Histamine: 1H-Imidazole-4-ethanamine. A depressor amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. [NIH] Histamine Agonists: Drugs that bind to and activate histamine receptors. Although they have been suggested for a variety of clinical applications histamine agonists have so far been more widely used in research than therapeutically. [NIH] Histamine Antagonists: Drugs that bind to but do not activate histamine receptors, thereby blocking the actions of histamine or histamine agonists. Classical antihistaminics block the histamine H1 receptors only. [NIH] Histidine: An essential amino acid important in a number of metabolic processes. It is required for the production of histamine. [NIH] Histidine Decarboxylase: An enzyme that catalyzes the decarboxylation of histidine to histamine and carbon dioxide. It requires pyridoxal phosphate in animal tissues, but not in microorganisms. EC 4.1.1.22. [NIH] Holidays: Days commemorating events. Holidays also include vacation periods. [NIH] Homeopathic remedies: Small doses of medicines, herbs, or both that are believed to stimulate the immune system. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small
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intestine. [NIH] Hormone Replacement Therapy: Therapeutic use of hormones to alleviate the effects of hormone deficiency. [NIH] Hormone therapy: Treatment of cancer by removing, blocking, or adding hormones. Also called endocrine therapy. [NIH] Host: Any animal that receives a transplanted graft. [NIH] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hybridization: The genetic process of crossbreeding to produce a hybrid. Hybrid nucleic acids can be formed by nucleic acid hybridization of DNA and RNA molecules. Protein hybridization allows for hybrid proteins to be formed from polypeptide chains. [NIH] Hybridomas: Cells artificially created by fusion of activated lymphocytes with neoplastic cells. The resulting hybrid cells are cloned and produce pure or "monoclonal" antibodies or T-cell products, identical to those produced by the immunologically competent parent, and continually grow and divide as the neoplastic parent. [NIH] Hydrocephalus: Excessive accumulation of cerebrospinal fluid within the cranium which may be associated with dilation of cerebral ventricles, intracranial hypertension; headache; lethargy; urinary incontinence; and ataxia (and in infants macrocephaly). This condition may be caused by obstruction of cerebrospinal fluid pathways due to neurologic abnormalities, intracranial hemorrhages; central nervous system infections; brain neoplasms; craniocerebral trauma; and other conditions. Impaired resorption of cerebrospinal fluid from the arachnoid villi results in a communicating form of hydrocephalus. Hydrocephalus ex-vacuo refers to ventricular dilation that occurs as a result of brain substance loss from cerebral infarction and other conditions. [NIH] Hydrochloric Acid: A strong corrosive acid that is commonly used as a laboratory reagent. It is formed by dissolving hydrogen chloride in water. Gastric acid is the hydrochloric acid component of gastric juice. [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] Hydrophilic: Readily absorbing moisture; hygroscopic; having strongly polar groups that readily interact with water. [EU] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU] 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] Hydroxysteroids: Steroids in which one or more hydroxy groups have been substituted for hydrogen atoms either within the ring skeleton or on any of the side chains. [NIH] Hygienic: Pertaining to hygiene, or conducive to health. [EU] Hyperammonemia: Metabolic disorder characterized by elevated level of ammonia in
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blood. [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] Hypercalcemia: Abnormally high level of calcium in the blood. [NIH] Hypercholesterolemia: Abnormally high levels of cholesterol in the blood. [NIH] Hyperglycemia: Abnormally high blood sugar. [NIH] Hyperglycemic Hyperosmolar Nonketotic Coma: A syndrome consisting of extreme hyperglycemia, serum hyperosmolarity and dehydration in the absence of ketosis and acidosis. [NIH] Hyperlipidemia: An excess of lipids in the blood. [NIH] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] 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] Hyperuricemia: A buildup of uric acid (a byproduct of metabolism) in the blood; a side effect of some anticancer drugs. [NIH] Hypoglycaemia: An abnormally diminished concentration of glucose in the blood, which may lead to tremulousness, cold sweat, piloerection, hypothermia, and headache, accompanied by irritability, confusion, hallucinations, bizarre behaviour, and ultimately, convulsions and coma. [EU] Hypoglycemia: Abnormally low blood sugar [NIH] Hypoglycemic: An orally active drug that produces a fall in blood glucose concentration. [NIH]
Hypoglycemic Agents: Agents which lower the blood glucose level. [NIH] Hypogonadism: Condition resulting from or characterized by abnormally decreased functional activity of the gonads, with retardation of growth and sexual development. [NIH] Hypolipidemic: A drug that lowers abnormally high plasma concentrations of cholesterol or triglycerides or both. [NIH] Hypotension: Abnormally low blood pressure. [NIH] Hypothalamic: Of or involving the hypothalamus. [EU] Hypothalamus: Ventral part of the diencephalon extending from the region of the optic chiasm to the caudal border of the mammillary bodies and forming the inferior and lateral walls of the third ventricle. [NIH] Hypothermia: Lower than normal body temperature, especially in warm-blooded animals; in man usually accidental or unintentional. [NIH] Hypothyroidism: Deficiency of thyroid activity. In adults, it is most common in women and is characterized by decrease in basal metabolic rate, tiredness and lethargy, sensitivity to cold, and menstrual disturbances. If untreated, it progresses to full-blown myxoedema. In
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infants, severe hypothyroidism leads to cretinism. In juveniles, the manifestations are intermediate, with less severe mental and developmental retardation and only mild symptoms of the adult form. When due to pituitary deficiency of thyrotropin secretion it is called secondary hypothyroidism. [EU] 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] Ibotenic Acid: Neurotoxic isoxazole substance found in Amanita muscaria and A. pantherina. It causes motor depression, ataxia, and changes in mood, perceptions and feelings, and is a potent excitatory amino acid agonist. [NIH] Ice Cream: A frozen dairy food made from cream or butterfat, milk, sugar, and flavorings. Frozen custard and French-type ice creams also contain eggs. [NIH] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Idiopathic: Describes a disease of unknown cause. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]
Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunity: Nonsusceptibility to the invasive or pathogenic microorganisms or to the toxic effect of antigenic substances. [NIH]
effects
of
foreign
Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] 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] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunosuppressive therapy: Therapy used to decrease the body's immune response, such as drugs given to prevent transplant rejection. [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]
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Implant radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called [NIH] Implantable pump: A small device installed under the skin to administer a steady dose of drugs. [NIH] Implantation: The insertion or grafting into the body of biological, living, inert, or radioactive material. [EU] Impotence: The inability to perform sexual intercourse. [NIH] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes. [NIH] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH] Incontinence: Inability to control the flow of urine from the bladder (urinary incontinence) or the escape of stool from the rectum (fecal incontinence). [NIH] Incubated: Grown in the laboratory under controlled conditions. (For instance, white blood cells can be grown in special conditions so that they attack specific cancer cells when returned to the body.) [NIH] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Indigestion: Poor digestion. Symptoms include heartburn, nausea, bloating, and gas. Also called dyspepsia. [NIH] Indomethacin: A non-steroidal anti-inflammatory agent (NSAID) that inhibits the enzyme cyclooxygenase necessary for the formation of prostaglandins and other autacoids. It also inhibits the motility of polymorphonuclear leukocytes. [NIH] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infancy: The period of complete dependency prior to the acquisition of competence in walking, talking, and self-feeding. [NIH] Infant Nutrition: Nutrition of children from birth to 2 years of age. [NIH] Infant, Newborn: An infant during the first month after birth. [NIH] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]
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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] Infiltration: The diffusion or accumulation in a tissue or cells of substances not normal to it or in amounts of the normal. Also, the material so accumulated. [EU] Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Inflammatory bowel disease: A general term that refers to the inflammation of the colon and rectum. Inflammatory bowel disease includes ulcerative colitis and Crohn's disease. [NIH]
Influenza: An acute viral infection involving the respiratory tract. It is marked by inflammation of the nasal mucosa, the pharynx, and conjunctiva, and by headache and severe, often generalized, myalgia. [NIH] Infuse: To pour (a liquid) into something. [EU] Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Infusion Pumps: Fluid propulsion systems driven mechanically, electrically, or osmotically that are used to inject (or infuse) over time agents into a patient or experimental animal; used routinely in hospitals to maintain a patent intravenous line, to administer antineoplastic agents and other drugs in thromboembolism, heart disease, diabetes mellitus (insulin infusion systems is also available), and other disorders. [NIH] Ingestion: Taking into the body by mouth [NIH] Inhalation: The drawing of air or other substances into the lungs. [EU] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Inlay: In dentistry, a filling first made to correspond with the form of a dental cavity and then cemented into the cavity. [NIH] Inner ear: The labyrinth, comprising the vestibule, cochlea, and semicircular canals. [NIH] Innervation: 1. The distribution or supply of nerves to a part. 2. The supply of nervous energy or of nerve stimulus sent to a part. [EU] Inorganic: Pertaining to substances not of organic origin. [EU] Inositol: An isomer of glucose that has traditionally been considered to be a B vitamin although it has an uncertain status as a vitamin and a deficiency syndrome has not been identified in man. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1379) Inositol phospholipids are important in signal transduction. [NIH] Inotropic: Affecting the force or energy of muscular contractions. [EU] Insecticides: Pesticides designed to control insects that are harmful to man. The insects may be directly harmful, as those acting as disease vectors, or indirectly harmful, as destroyers of crops, food products, or textile fabrics. [NIH] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Insomnia: Difficulty in going to sleep or getting enough sleep. [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
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a drug to control insulin-dependent diabetes mellitus. [NIH] Insulin Infusion Systems: Portable or implantable devices for infusion of insulin. Includes open-loop systems which may be patient-operated or controlled by a pre-set program and are designed for constant delivery of small quantities of insulin, increased during food ingestion, and closed-loop systems which deliver quantities of insulin automatically based on an electronic glucose sensor. [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] Insulin-Like Growth Factor I: A well-characterized basic peptide believed to be secreted by the liver and to circulate in the blood. It has growth-regulating, insulin-like, and mitogenic activities. This growth factor has a major, but not absolute, dependence on somatotropin. It is believed to be mainly active in adults in contrast to insulin-like growth factor II, which is a major fetal growth factor. [NIH] Integrins: A family of transmembrane glycoproteins consisting of noncovalent heterodimers. They interact with a wide variety of ligands including extracellular matrix glycoproteins, complement, and other cells, while their intracellular domains interact with the cytoskeleton. The integrins consist of at least three identified families: the cytoadhesin receptors, the leukocyte adhesion receptors, and the very-late-antigen receptors. Each family contains a common beta-subunit combined with one or more distinct alpha-subunits. These receptors participate in cell-matrix and cell-cell adhesion in many physiologically important processes, including embryological development, hemostasis, thrombosis, wound healing, immune and nonimmune defense mechanisms, and oncogenic transformation. [NIH] Interferon: A biological response modifier (a substance that can improve the body's natural response to disease). Interferons interfere with the division of cancer cells and can slow tumor growth. There are several types of interferons, including interferon-alpha, -beta, and gamma. These substances are normally produced by the body. They are also made in the laboratory for use in treating cancer and other diseases. [NIH] Interferon-alpha: One of the type I interferons produced by peripheral blood leukocytes or lymphoblastoid cells when exposed to live or inactivated virus, double-stranded RNA, or bacterial products. It is the major interferon produced by virus-induced leukocyte cultures and, in addition to its pronounced antiviral activity, it causes activation of NK cells. [NIH] Interindividual: Occurring between two or more individuals. [EU] Interleukin-6: Factor that stimulates the growth and differentiation of human B-cells and is also a growth factor for hybridomas and plasmacytomas. It is produced by many different cells including T-cells, monocytes, and fibroblasts. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Internal Medicine: A medical specialty concerned with the diagnosis and treatment of diseases of the internal organ systems of adults. [NIH] Internal radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called brachytherapy, implant radiation, or interstitial radiation therapy. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intestinal: Having to do with the intestines. [NIH] Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH]
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Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intracranial Embolism: The sudden obstruction of a blood vessel by an embolus. [NIH] Intracranial Embolism and Thrombosis: Embolism or thrombosis involving blood vessels which supply intracranial structures. Emboli may originate from extracranial or intracranial sources. Thrombosis may occur in arterial or venous structures. [NIH] Intracranial Hemorrhages: Bleeding within the intracranial cavity, including hemorrhages in the brain and within the cranial epidural, subdural, and subarachnoid spaces. [NIH] Intracranial Hypertension: Increased pressure within the cranial vault. This may result from several conditions, including hydrocephalus; brain edema; intracranial masses; severe systemic hypertension; pseudotumor cerebri; and other disorders. [NIH] Intrahepatic: Within the liver. [NIH] Intraindividual: Being or occurring within the individual. [EU] Intramuscular: IM. Within or into muscle. [NIH] Intraperitoneal: IP. Within the peritoneal cavity (the area that contains the abdominal organs). [NIH] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]
Invertebrates: Animals that have no spinal column. [NIH] Involuntary: Reaction occurring without intention or volition. [NIH] Ion Channels: Gated, ion-selective glycoproteins that traverse membranes. The stimulus for channel gating can be a membrane potential, drug, transmitter, cytoplasmic messenger, or a mechanical deformation. Ion channels which are integral parts of ionotropic neurotransmitter receptors are not included. [NIH] Ion Transport: The movement of ions across energy-transducing cell membranes. Transport can be active or passive. Passive ion transport (facilitated diffusion) derives its energy from the concentration gradient of the ion itself and allows the transport of a single solute in one direction (uniport). Active ion transport is usually coupled to an energy-yielding chemical or photochemical reaction such as ATP hydrolysis. This form of primary active transport is called an ion pump. Secondary active transport utilizes the voltage and ion gradients produced by the primary transport to drive the cotransport of other ions or molecules. These may be transported in the same (symport) or opposite (antiport) direction. [NIH] Ionizing: Radiation comprising charged particles, e. g. electrons, protons, alpha-particles, etc., having sufficient kinetic energy to produce ionization by collision. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Irradiation: The use of high-energy radiation from x-rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive
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substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Irradiation is also called radiation therapy, radiotherapy, and x-ray therapy. [NIH] Irritable Bowel Syndrome: A disorder that comes and goes. Nerves that control the muscles in the GI tract are too active. The GI tract becomes sensitive to food, stool, gas, and stress. Causes abdominal pain, bloating, and constipation or diarrhea. Also called spastic colon or mucous colitis. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Ischemic stroke: A condition in which the blood supply to part of the brain is cut off. Also called "plug-type" strokes. Blocked arteries starve areas of the brain controlling sight, speech, sensation, and movement so that these functions are partially or completely lost. Ischemic stroke is the most common type of stroke, accounting for 80 percent of all strokes. Most ischemic strokes are caused by a blood clot called a thrombus, which blocks blood flow in the arteries feeding the brain, usually the carotid artery in the neck, the major vessel bringing blood to the brain. When it becomes blocked, the risk of stroke is very high. [NIH] Islet: Cell producing insulin in pancreas. [NIH] Isozymes: The multiple forms of a single enzyme. [NIH] Jejunostomy: Surgical formation of an opening through the abdominal wall into the jejunum, usually for enteral hyperalimentation. [NIH] Jet lag: Symptoms produced in human beings by fast travel through large meridian difference. [NIH] Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [NIH] Kainate: Glutamate receptor. [NIH] Kainic Acid: (2S-(2 alpha,3 beta,4 beta))-2-Carboxy-4-(1-methylethenyl)-3-pyrrolidineacetic acid. Ascaricide obtained from the red alga Digenea simplex. It is a potent excitatory amino acid agonist at some types of excitatory amino acid receptors and has been used to discriminate among receptor types. Like many excitatory amino acid agonists it can cause neurotoxicity and has been used experimentally for that purpose. [NIH] Karyotype: The characteristic chromosome complement of an individual, race, or species as defined by their number, size, shape, etc. [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] Ketamine: A cyclohexanone derivative used for induction of anesthesia. Its mechanism of action is not well understood, but ketamine can block NMDA receptors (receptors, NMethyl-D-Aspartate) and may interact with sigma receptors. [NIH] Keto: It consists of 8 carbon atoms and within the endotoxins, it connects poysaccharide and lipid A. [NIH] Ketone Bodies: Chemicals that the body makes when there is not enough insulin in the blood and it must break down fat for its energy. Ketone bodies can poison and even kill body cells. When the body does not have the help of insulin, the ketones build up in the blood and then "spill" over into the urine so that the body can get rid of them. The body can also rid itself of one type of ketone, called acetone, through the lungs. This gives the breath a fruity odor. Ketones that build up in the body for a long time lead to serious illness and coma. [NIH] Ketonuria: Having ketone bodies in the urine; a warning sign of diabetic ketoacidosis
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(DKA). [NIH] Ketosis: A condition of having ketone bodies build up in body tissues and fluids. The signs of ketosis are nausea, vomiting, and stomach pain. Ketosis can lead to ketoacidosis. [NIH] Kidney Cortex: The outer zone of the kidney, beneath the capsule, consisting of kidney glomerulus; kidney tubules, distal; and kidney tubules, proximal. [NIH] Kidney Disease: Any one of several chronic conditions that are caused by damage to the cells of the kidney. People who have had diabetes for a long time may have kidney damage. Also called nephropathy. [NIH] Kidney Failure: The inability of a kidney to excrete metabolites at normal plasma levels under conditions of normal loading, or the inability to retain electrolytes under conditions of normal intake. In the acute form (kidney failure, acute), it is marked by uremia and usually by oliguria or anuria, with hyperkalemia and pulmonary edema. The chronic form (kidney failure, chronic) is irreversible and requires hemodialysis. [NIH] Kidney Failure, Acute: A clinical syndrome characterized by a sudden decrease in glomerular filtration rate, often to values of less than 1 to 2 ml per minute. It is usually associated with oliguria (urine volumes of less than 400 ml per day) and is always associated with biochemical consequences of the reduction in glomerular filtration rate such as a rise in blood urea nitrogen (BUN) and serum creatinine concentrations. [NIH] Kidney Failure, Chronic: An irreversible and usually progressive reduction in renal function in which both kidneys have been damaged by a variety of diseases to the extent that they are unable to adequately remove the metabolic products from the blood and regulate the body's electrolyte composition and acid-base balance. Chronic kidney failure requires hemodialysis or surgery, usually kidney transplantation. [NIH] Kidney stone: A stone that develops from crystals that form in urine and build up on the inner surfaces of the kidney, in the renal pelvis, or in the ureters. [NIH] Kidney Transplantation: The transference of a kidney from one human or animal to another. [NIH] Kinetic: Pertaining to or producing motion. [EU] Labyrinth: The internal ear; the essential part of the organ of hearing. It consists of an osseous and a membranous portion. [NIH] Laceration: 1. The act of tearing. 2. A torn, ragged, mangled wound. [EU] Lactation: The period of the secretion of milk. [EU] Lag: The time elapsing between application of a stimulus and the resulting reaction. [NIH] Laminin: Large, noncollagenous glycoprotein with antigenic properties. It is localized in the basement membrane lamina lucida and functions to bind epithelial cells to the basement membrane. Evidence suggests that the protein plays a role in tumor invasion. [NIH] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Larynx: An irregularly shaped, musculocartilaginous tubular structure, lined with mucous membrane, located at the top of the trachea and below the root of the tongue and the hyoid bone. It is the essential sphincter guarding the entrance into the trachea and functioning secondarily as the organ of voice. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH]
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Lathyrism: A paralytic condition of the legs caused by ingestion of lathyrogens, especially beta-aminopropionitrile, found in the seeds of plants of the genus Lathyrus. [NIH] Laxative: An agent that acts to promote evacuation of the bowel; a cathartic or purgative. [EU]
Leprosy: A chronic granulomatous infection caused by Mycobacterium leprae. The granulomatous lesions are manifested in the skin, the mucous membranes, and the peripheral nerves. Two polar or principal types are lepromatous and tuberculoid. [NIH] Leptin: A 16-kD peptide hormone secreted from white adipocytes and implicated in the regulation of food intake and energy balance. Leptin provides the key afferent signal from fat cells in the feedback system that controls body fat stores. [NIH] Lesion: An area of abnormal tissue change. [NIH] Lethal: Deadly, fatal. [EU] Lethargy: Abnormal drowsiness or stupor; a condition of indifference. [EU] Leucine: An essential branched-chain amino acid important for hemoglobin formation. [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] Library Services: Services offered to the library user. They include reference and circulation. [NIH]
Lice: A general name for small, wingless, parasitic insects, previously of the order Phthiraptera. Though exact taxonomy is still controversial, they can be grouped in the orders Anoplura (sucking lice), Mallophaga (biting lice), and Rhynchophthirina (elephant lice). [NIH] Lidocaine: A local anesthetic and cardiac depressant used as an antiarrhythmia agent. Its actions are more intense and its effects more prolonged than those of procaine but its duration of action is shorter than that of bupivacaine or prilocaine. [NIH] Life cycle: The successive stages through which an organism passes from fertilized ovum or spore to the fertilized ovum or spore of the next generation. [NIH] Life Expectancy: A figure representing the number of years, based on known statistics, to which any person of a given age may reasonably expect to live. [NIH] Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] Ligands: A RNA simulation method developed by the MIT. [NIH] Ligation: Application of a ligature to tie a vessel or strangulate a part. [NIH] Limbic: Pertaining to a limbus, or margin; forming a border around. [EU] Limbic System: A set of forebrain structures common to all mammals that is defined functionally and anatomically. It is implicated in the higher integration of visceral, olfactory, and somatic information as well as homeostatic responses including fundamental survival behaviors (feeding, mating, emotion). For most authors, it includes the amygdala, epithalamus, gyrus cinguli, hippocampal formation (see hippocampus), hypothalamus, parahippocampal gyrus, septal nuclei, anterior nuclear group of thalamus, and portions of the basal ganglia. (Parent, Carpenter's Human Neuroanatomy, 9th ed, p744; NeuroNames, http://rprcsgi.rprc.washington.edu/neuronames/index.html (September 2, 1998)). [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]
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Lipid: Fat. [NIH] Lipid A: Lipid A is the biologically active component of lipopolysaccharides. It shows strong endotoxic activity and exhibits immunogenic properties. [NIH] Lipolysis: The hydrolysis of lipids. [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] Lithium: An element in the alkali metals family. It has the atomic symbol Li, atomic number 3, and atomic weight 6.94. Salts of lithium are used in treating manic-depressive disorders. [NIH]
Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver Transplantation: The transference of a part of or an entire liver from one human or animal to another. [NIH] Lobe: A portion of an organ such as the liver, lung, breast, or brain. [NIH] 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] Locomotion: Movement or the ability to move from one place or another. It can refer to humans, vertebrate or invertebrate animals, and microorganisms. [NIH] Longitudinal Studies: Studies in which variables relating to an individual or group of individuals are assessed over a period of time. [NIH] Longitudinal study: Also referred to as a "cohort study" or "prospective study"; the analytic method of epidemiologic study in which subsets of a defined population can be identified who are, have been, or in the future may be exposed or not exposed, or exposed in different degrees, to a factor or factors hypothesized to influence the probability of occurrence of a given disease or other outcome. The main feature of this type of study is to observe large numbers of subjects over an extended time, with comparisons of incidence rates in groups that differ in exposure levels. [NIH] Loop: A wire usually of platinum bent at one end into a small loop (usually 4 mm inside diameter) and used in transferring microorganisms. [NIH] Low-density lipoprotein: Lipoprotein that contains most of the cholesterol in the blood. LDL carries cholesterol to the tissues of the body, including the arteries. A high level of LDL increases the risk of heart disease. LDL typically contains 60 to 70 percent of the total serum cholesterol and both are directly correlated with CHD risk. [NIH] Lumbar: Pertaining to the loins, the part of the back between the thorax and the pelvis. [EU] Luteal Phase: The period of the menstrual cycle that begins with ovulation and ends with menstruation. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along
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lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]
Lymphadenitis: Inflammation of the lymph nodes. [NIH] Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] Lymphoblastic: One of the most aggressive types of non-Hodgkin lymphoma. [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 Count: A count of the number of lymphocytes in the blood. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [NIH] Lymphoproliferative: Disorders characterized by proliferation of lymphoid tissue, general or unspecified. [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] Macula: A stain, spot, or thickening. Often used alone to refer to the macula retinae. [EU] Macula Lutea: An oval area in the retina, 3 to 5 mm in diameter, usually located temporal to the superior pole of the eye and slightly below the level of the optic disk. [NIH] Macular Degeneration: Degenerative changes in the macula lutea of the retina. [NIH] Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [NIH] Magnetic Resonance Spectroscopy: Spectroscopic method of measuring the magnetic moment of elementary particles such as atomic nuclei, protons or electrons. It is employed in clinical applications such as NMR Tomography (magnetic resonance imaging). [NIH] Maintenance therapy: Treatment that is given to help a primary (original) treatment keep working. Maintenance therapy is often given to help keep cancer in remission. [NIH] Malabsorption: Impaired intestinal absorption of nutrients. [EU] Malabsorption syndrome: A group of symptoms such as gas, bloating, abdominal pain, and diarrhea resulting from the body's inability to properly absorb nutrients. [NIH] Malaria: A protozoan disease caused in humans by four species of the genus Plasmodium (P. falciparum (malaria, falciparum), P. vivax (malaria, vivax), P. ovale, and P. malariae) and transmitted by the bite of an infected female mosquito of the genus Anopheles. Malaria is endemic in parts of Asia, Africa, Central and South America, Oceania, and certain Caribbean islands. It is characterized by extreme exhaustion associated with paroxysms of high fever, sweating, shaking chills, and anemia. Malaria in animals is caused by other species of plasmodia. [NIH]
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Malaria, Falciparum: Malaria caused by Plasmodium falciparum. This is the severest form of malaria and is associated with the highest levels of parasites in the blood. This disease is characterized by irregularly recurring febrile paroxysms that in extreme cases occur with acute cerebral, renal, or gastrointestinal manifestations. [NIH] Malaria, Vivax: Malaria caused by Plasmodium vivax. This form of malaria is less severe than malaria, falciparum, but there is a higher probability for relapses to occur. Febrile paroxysms often occur every other day. [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]
Mammary: Pertaining to the mamma, or breast. [EU] Manic: Affected with mania. [EU] Manic-depressive psychosis: One of a group of psychotic reactions, fundamentally marked by severe mood swings and a tendency to remission and recurrence. [NIH] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] Maternal Exposure: Exposure of the female parent, human or animal, to potentially harmful chemical, physical, or biological agents in the environment or to environmental factors that may include ionizing radiation, pathogenic organisms, or toxic chemicals that may affect offspring. It includes pre-conception maternal exposure. [NIH] Meat: The edible portions of any animal used for food including domestic mammals (the major ones being cattle, swine, and sheep) along with poultry, fish, shellfish, and game. [NIH]
Meatus: A canal running from the internal auditory foramen through the petrous portion of the temporal bone. It gives passage to the facial and auditory nerves together with the auditory branch of the basilar artery and the internal auditory veins. [NIH] Medial: Lying near the midsaggital plane of the body; opposed to lateral. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] Medical Records: Recording of pertinent information concerning patient's illness or illnesses. [NIH] Medicament: A medicinal substance or agent. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Medullary: Pertaining to the marrow or to any medulla; resembling marrow. [EU] Meiosis: A special method of cell division, occurring in maturation of the germ cells, by means of which each daughter nucleus receives half the number of chromosomes characteristic of the somatic cells of the species. [NIH] Melanin: The substance that gives the skin its color. [NIH] Melanocytes: Epidermal dendritic pigment cells which control long-term morphological color changes by alteration in their number or in the amount of pigment they produce and
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store in the pigment containing organelles called melanosomes. Melanophores are larger cells which do not exist in mammals. [NIH] Melanoma: A form of skin cancer that arises in melanocytes, the cells that produce pigment. Melanoma usually begins in a mole. [NIH] Memantine: Amantadine derivative that has some dopaminergic effects. It has been proposed as an antiparkinson agent. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells. [NIH] 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] Menstrual Cycle: The period of the regularly recurring physiologic changes in the endometrium occurring during the reproductive period in human females and some primates and culminating in partial sloughing of the endometrium (menstruation). [NIH] Menstruation: The normal physiologic discharge through the vagina of blood and mucosal tissues from the nonpregnant uterus. [NIH] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH] Mental Processes: Conceptual functions or thinking in all its forms. [NIH] Mesenchymal: Refers to cells that develop into connective tissue, blood vessels, and lymphatic tissue. [NIH] Mesolimbic: Inner brain region governing emotion and drives. [NIH] Metabolic disorder: A condition in which normal metabolic processes are disrupted, usually because of a missing enzyme. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Metabotropic: A glutamate receptor which triggers an increase in production of 2 intracellular messengers: diacylglycerol and inositol 1, 4, 5-triphosphate. [NIH] Metallothionein: A low-molecular-weight (approx. 10 kD) protein occurring in the cytoplasm of kidney cortex and liver. It is rich in cysteinyl residues and contains no aromatic amino acids. Metallothionein shows high affinity for bivalent heavy metals. [NIH] Metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors" and contain cells that are like those in the original (primary) tumor. The plural is metastases. [NIH] Metastatic: Having to do with metastasis, which is the spread of cancer from one part of the body to another. [NIH] Methionine: A sulfur containing essential amino acid that is important in many body functions. It is a chelating agent for heavy metals. [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH]
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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] Microdialysis: A technique for measuring extracellular concentrations of substances in tissues, usually in vivo, by means of a small probe equipped with a semipermeable membrane. Substances may also be introduced into the extracellular space through the membrane. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Middle Cerebral Artery: The largest and most complex of the cerebral arteries. Branches of the middle cerebral artery supply the insular region, motor and premotor areas, and large regions of the association cortex. [NIH] Mifepristone: A progestational and glucocorticoid hormone antagonist. Its inhibition of progesterone induces bleeding during the luteal phase and in early pregnancy by releasing endogenous prostaglandins from the endometrium or decidua. As a glucocorticoid receptor antagonist, the drug has been used to treat hypercortisolism in patients with nonpituitary Cushing syndrome. [NIH] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Milligram: A measure of weight. A milligram is approximately 450,000-times smaller than a pound and 28,000-times smaller than an ounce. [NIH] 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] Mitochondria: Parts of a cell where aerobic production (also known as cell respiration) takes place. [NIH] Mitochondrial Swelling: Increase in volume of mitochondria due to an influx of fluid; it occurs in hypotonic solutions due to osmotic pressure and in isotonic solutions as a result of altered permeability of the membranes of respiring mitochondria. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Mobilization: The process of making a fixed part or stored substance mobile, as by separating a part from surrounding structures to make it accessible for an operative procedure or by causing release into the circulation for body use of a substance stored in the body. [EU] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Modulator: A specific inductor that brings out characteristics peculiar to a definite region. [EU]
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Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecular Structure: The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds. [NIH] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monocyte: A type of white blood cell. [NIH] Monotherapy: A therapy which uses only one drug. [EU] Morphine: The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle. [NIH] Morphological: Relating to the configuration or the structure of live organs. [NIH] Motility: The ability to move spontaneously. [EU] Motion Sickness: Sickness caused by motion, as sea sickness, train sickness, car sickness, and air sickness. [NIH] Movement Disorders: Syndromes which feature dyskinesias as a cardinal manifestation of the disease process. Included in this category are degenerative, hereditary, post-infectious, medication-induced, post-inflammatory, and post-traumatic conditions. [NIH] Mucus: The viscous secretion of mucous membranes. It contains mucin, white blood cells, water, inorganic salts, and exfoliated cells. [NIH] Multidrug resistance: Adaptation of tumor cells to anticancer drugs in ways that make the drugs less effective. [NIH] Muscimol: Neurotoxic isoxazole isolated from Amanita muscaria and A. phalloides and also obtained by decarboxylation of ibotenic acid. It is a potent agonist at GABA-A receptors and is used mainly as an experimental tool in animal and tissue studies. [NIH] Muscle 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] Muscular Atrophy: Derangement in size and number of muscle fibers occurring with aging, reduction in blood supply, or following immobilization, prolonged weightlessness, malnutrition, and particularly in denervation. [NIH] Muscular Dystrophies: A general term for a group of inherited disorders which are characterized by progressive degeneration of skeletal muscles. [NIH] Musculature: The muscular apparatus of the body, or of any part of it. [EU] Myalgia: Pain in a muscle or muscles. [EU] Myasthenia: Muscular debility; any constitutional anomaly of muscle. [EU] Myocardial infarction: Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle
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known as cardiac muscle. [NIH] Myoclonus: Involuntary shock-like contractions, irregular in rhythm and amplitude, followed by relaxation, of a muscle or a group of muscles. This condition may be a feature of some central nervous systems diseases (e.g., epilepsy, myoclonic). Nocturnal myoclonus may represent a normal physiologic event or occur as the principal feature of the nocturnal myoclonus syndrome. (From Adams et al., Principles of Neurology, 6th ed, pp102-3). [NIH] Myopathy: Any disease of a muscle. [EU] Myotonic Dystrophy: A condition presenting muscle weakness and wasting which may be progressive. [NIH] Naive: Used to describe an individual who has never taken a certain drug or class of drugs (e. g., AZT-naive, antiretroviral-naive), or to refer to an undifferentiated immune system cell. [NIH] Narcotic: 1. Pertaining to or producing narcosis. 2. An agent that produces insensibility or stupor, applied especially to the opioids, i.e. to any natural or synthetic drug that has morphine-like actions. [EU] Nasal Mucosa: The mucous membrane lining the nasal cavity. [NIH] Nasogastric: The process of passing a small, flexible plastic tube through the nose or mouth into the stomach or small intestine. [NIH] Natural selection: A part of the evolutionary process resulting in the survival and reproduction of the best adapted individuals. [NIH] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU] Neoplasia: Abnormal and uncontrolled cell growth. [NIH] Neoplasm: A new growth of benign or malignant tissue. [NIH] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] Nephropathy: Disease of the kidneys. [EU] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nerve Endings: Specialized terminations of peripheral neurons. Nerve endings include neuroeffector junction(s) by which neurons activate target organs and sensory receptors which transduce information from the various sensory modalities and send it centrally in the nervous system. Presynaptic nerve endings are presynaptic terminals. [NIH]
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Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Nervousness: Excessive excitability and irritability, with mental and physical unrest. [EU] 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]
Neural tube defects: These defects include problems stemming from fetal development of the spinal cord, spine, brain, and skull, and include birth defects such as spina bifida, anencephaly, and encephalocele. Neural tube defects occur early in pregnancy at about 4 to 6 weeks, usually before a woman knows she is pregnant. Many babies with neural tube defects have difficulty walking and with bladder and bowel control. [NIH] Neuralgia: Intense or aching pain that occurs along the course or distribution of a peripheral or cranial nerve. [NIH] Neuroblastoma: Cancer that arises in immature nerve cells and affects mostly infants and children. [NIH] Neurodegenerative Diseases: Hereditary and sporadic conditions which are characterized by progressive nervous system dysfunction. These disorders are often associated with atrophy of the affected central or peripheral nervous system structures. [NIH] Neuroeffector Junction: The synapse between a neuron (presynaptic) and an effector cell other than another neuron (postsynaptic). Neuroeffector junctions include synapses onto muscles and onto secretory cells. [NIH] Neuroendocrine: Having to do with the interactions between the nervous system and the endocrine system. Describes certain cells that release hormones into the blood in response to stimulation of the nervous system. [NIH] Neuroendocrine tumor: A tumor derived from cells that release a hormone in response to a signal from the nervous system. Some examples of neuroendocrine tumors are carcinoid tumors, islet cell tumors, medullary thyroid carcinoma, and pheochromocytoma. These tumors secrete hormones in excess, causing a variety of symptoms. [NIH] Neuroendocrinology: The study of the anatomical and functional relationships between the nervous system and the endocrine system. [NIH] Neurogenic: Loss of bladder control caused by damage to the nerves controlling the bladder. [NIH] Neuroglia: The non-neuronal cells of the nervous system. They are divided into macroglia (astrocytes, oligodendroglia, and schwann cells) and microglia. They not only provide physical support, but also respond to injury, regulate the ionic and chemical composition of the extracellular milieu, participate in the blood-brain and blood-retina barriers, form the myelin insulation of nervous pathways, guide neuronal migration during development, and exchange metabolites with neurons. Neuroglia have high-affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitters, but their role in signaling (as in many other functions) is unclear. [NIH] Neuroleptic: A term coined to refer to the effects on cognition and behaviour of antipsychotic drugs, which produce a state of apathy, lack of initiative, and limited range of emotion and in psychotic patients cause a reduction in confusion and agitation and normalization of psychomotor activity. [EU] Neurologic: Having to do with nerves or the nervous system. [NIH] Neuromuscular: Pertaining to muscles and nerves. [EU]
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Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neuropathy: A problem in any part of the nervous system except the brain and spinal cord. Neuropathies can be caused by infection, toxic substances, or disease. [NIH] Neuropeptides: Peptides released by neurons as intercellular messengers. Many neuropeptides are also hormones released by non-neuronal cells. [NIH] Neuropharmacology: The branch of pharmacology dealing especially with the action of drugs upon various parts of the nervous system. [NIH] Neurophysiology: The scientific discipline concerned with the physiology of the nervous system. [NIH] Neuroprotective Agents: Drugs intended to prevent damage to the brain or spinal cord from ischemia, stroke, convulsions, or trauma. Some must be administered before the event, but others may be effective for some time after. They act by a variety of mechanisms, but often directly or indirectly minimize the damage produced by endogenous excitatory amino acids. [NIH] Neuropsychological Tests: Tests designed to assess neurological function associated with certain behaviors. They are used in diagnosing brain dysfunction or damage and central nervous system disorders or injury. [NIH] Neuroretinitis: Inflammation of the optic nerve head and adjacent retina. [NIH] Neurosis: Functional derangement due to disorders of the nervous system which does not affect the psychic personality of the patient. [NIH] Neurosurgeon: A doctor who specializes in surgery on the brain, spine, and other parts of the nervous system. [NIH] Neurotoxicity: The tendency of some treatments to cause damage to the nervous system. [NIH]
Neurotransmitters: Endogenous signaling molecules that alter the behavior of neurons or effector cells. Neurotransmitter is used here in its most general sense, including not only messengers that act directly to regulate ion channels, but also those that act through second messenger systems, and those that act at a distance from their site of release. Included are neuromodulators, neuroregulators, neuromediators, and neurohumors, whether or not acting at synapses. [NIH] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] Neutrophils: Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. [NIH] Niacin: Water-soluble vitamin of the B complex occurring in various animal and plant tissues. Required by the body for the formation of coenzymes NAD and NADP. Has pellagra-curative, vasodilating, and antilipemic properties. [NIH] Nicotine: Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in
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tobacco smoke. [NIH] Nifedipine: A potent vasodilator agent with calcium antagonistic action. It is a useful antianginal agent that also lowers blood pressure. The use of nifedipine as a tocolytic is being investigated. [NIH] 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 next. [NIH] Nucleic Acid Hybridization: The process whereby two single-stranded polynucleotides form a double-stranded molecule, with hydrogen bonding between the complementary bases in the two strains. [NIH] Nucleotidases: A class of enzymes that catalyze the conversion of a nucleotide and water to a nucleoside and orthophosphate. EC 3.1.3.-. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nutrition Assessment: Evaluation and measurement of nutritional variables in order to assess the level of nutrition or the nutritional status of the individual. Nutrition surveys may be used in making the assessment. [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
Dictionary 343
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] Occupational Health: The promotion and maintenance of physical and mental health in the work environment. [NIH] Octreotide: A potent, long-acting somatostatin octapeptide analog which has a wide range of physiological actions. It inhibits growth hormone secretion, is effective in the treatment of hormone-secreting tumors from various organs, and has beneficial effects in the management of many pathological states including diabetes mellitus, orthostatic hypertension, hyperinsulinism, hypergastrinemia, and small bowel fistula. [NIH] Ocular: 1. Of, pertaining to, or affecting the eye. 2. Eyepiece. [EU] Ointments: Semisolid preparations used topically for protective emollient effects or as a vehicle for local administration of medications. Ointment bases are various mixtures of fats, waxes, animal and plant oils and solid and liquid hydrocarbons. [NIH] Oligoelement: A chemical substance, minute amounts of which can be found in living organisms. [EU] Oliguria: Clinical manifestation of the urinary system consisting of a decrease in the amount of urine secreted. [NIH] Oncogene: A gene that normally directs cell growth. If altered, an oncogene can promote or allow the uncontrolled growth of cancer. Alterations can be inherited or caused by an environmental exposure to carcinogens. [NIH] Oncogenic: Chemical, viral, radioactive or other agent that causes cancer; carcinogenic. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Ophthalmic: Pertaining to the eye. [EU] Opium: The air-dried exudate from the unripe seed capsule of the opium poppy, Papaver somniferum, or its variant, P. album. It contains a number of alkaloids, but only a few morphine, codeine, and papaverine - have clinical significance. Opium has been used as an analgesic, antitussive, antidiarrheal, and antispasmodic. [NIH] Opportunistic Infections: An infection caused by an organism which becomes pathogenic under certain conditions, e.g., during immunosuppression. [NIH] Opsin: A visual pigment protein found in the retinal rods. It combines with retinaldehyde to form rhodopsin. [NIH] Optic Chiasm: The X-shaped structure formed by the meeting of the two optic nerves. At the optic chiasm the fibers from the medial part of each retina cross to project to the other side of the brain while the lateral retinal fibers continue on the same side. As a result each half of the brain receives information about the contralateral visual field from both eyes. [NIH]
Optic Disk: The portion of the optic nerve seen in the fundus with the ophthalmoscope. It is formed by the meeting of all the retinal ganglion cell axons as they enter the optic nerve. [NIH]
Optic Nerve: The 2nd cranial nerve. The optic nerve conveys visual information from the
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retina to the brain. The nerve carries the axons of the retinal ganglion cells which sort at the optic chiasm and continue via the optic tracts to the brain. The largest projection is to the lateral geniculate nuclei; other important targets include the superior colliculi and the suprachiasmatic nuclei. Though known as the second cranial nerve, it is considered part of the central nervous system. [NIH] Oral Health: The optimal state of the mouth and normal functioning of the organs of the mouth without evidence of disease. [NIH] Organizational Culture: Beliefs and values shared by all members of the organization. These shared values are reflected in the day to day operations of the organization. [NIH] Orgasm: The crisis of sexual excitement in either humans or animals. [NIH] Orthostatic: Pertaining to or caused by standing erect. [EU] Osmotic: Pertaining to or of the nature of osmosis (= the passage of pure solvent from a solution of lesser to one of greater solute concentration when the two solutions are separated by a membrane which selectively prevents the passage of solute molecules, but is permeable to the solvent). [EU] Osteoarthritis: Degeneration of articular cartilage. Primary osteoarthritis is very common in older persons, especially affecting weight-bearing joints. Articular cartilage becomes soft, frayed and thinned. [NIH] Osteoporosis: Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal osteoporosis and age-related (or senile) osteoporosis. [NIH] Outpatient: A patient who is not an inmate of a hospital but receives diagnosis or treatment in a clinic or dispensary connected with the hospital. [NIH] Ovalbumin: An albumin obtained from the white of eggs. It is a member of the serpin superfamily. [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] Overdosage: 1. The administration of an excessive dose. 2. The condition resulting from an excessive dose. [EU] Overdose: An accidental or deliberate dose of a medication or street drug that is in excess of what is normally used. [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] Oxalate: A chemical that combines with calcium in urine to form the most common type of kidney stone (calcium oxalate stone). [NIH] Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]
Oxidative metabolism: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as aerobic respiration, cell respiration, or aerobic metabolism. [NIH]
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Oximetry: The determination of oxygen-hemoglobin saturation of blood either by withdrawing a sample and passing it through a classical photoelectric oximeter or by electrodes attached to some translucent part of the body like finger, earlobe, or skin fold. It includes non-invasive oxygen monitoring by pulse oximetry. [NIH] Oxygen Consumption: The oxygen consumption is determined by calculating the difference between the amount of oxygen inhaled and exhaled. [NIH] Oxygenation: The process of supplying, treating, or mixing with oxygen. No:1245 oxygenation the process of supplying, treating, or mixing with oxygen. [EU] Oxytocin: A nonapeptide posterior pituitary hormone that causes uterine contractions and stimulates lactation. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Palsy: Disease of the peripheral nervous system occurring usually after many years of increased lead absorption. [NIH] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreas Transplant: A surgical procedure that involves replacing the pancreas of a person who has diabetes with a healthy pancreas that can make insulin. The healthy pancreas comes from a donor who has just died or from a living relative. A person can donate half a pancreas and still live normally. [NIH] Pancreas Transplantation: The transference of a pancreas from one human or animal to another. [NIH] Pancreatectomy: Surgery to remove the pancreas. In a total pancreatectomy, a portion of the stomach, the duodenum, common bile duct, gallbladder, spleen, and nearby lymph nodes also are removed. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Pancreatic cancer: Cancer of the pancreas, a salivary gland of the abdomen. [NIH] Pancreatic Insufficiency: Absence of or reduced pancreatic exocrine secretion into the duodenum and resultant poor digestion of lipids, vitamins, nitrogen, and carbohydrates. [NIH]
Pancreatic Polypeptide: A 36-amino acid polypeptide with physiological regulatory functions. It is secreted by pancreatic tissue. Plasma pancreatic polypeptide increases after ingestion of food, with age, and in disease states. A lack of pancreatic polypeptide in the islets of Langerhans has been associated with the obese syndrome in rats and mice. [NIH] Papilloma: A benign epithelial neoplasm which may arise from the skin, mucous membranes or glandular ducts. [NIH] Paralysis: Loss of ability to move all or part of the body. [NIH] Parasite: An animal or a plant that lives on or in an organism of another species and gets at least some of its nutrition from that other organism. [NIH] Parasitic: Having to do with or being a parasite. A parasite is an animal or a plant that lives on or in an organism of another species and gets at least some of its nutrients from it. [NIH] Parasitism: A) The mode of life of a parasite; b) The relationship between an organism (parasite) that derives benefits from, and at the expense of, another organism (host). [NIH] Parathyroid: 1. Situated beside the thyroid gland. 2. One of the parathyroid glands. 3. A sterile preparation of the water-soluble principle(s) of the parathyroid glands, ad-ministered
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parenterally as an antihypocalcaemic, hypoparathyroidism with tetany. [EU]
especially
in
the
treatment
of
acute
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] 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] Parkinsonism: A group of neurological disorders characterized by hypokinesia, tremor, and muscular rigidity. [EU] Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Particle: A tiny mass of material. [EU] Patent ductus arteriosus: Abnormal persistence of the opening in the arterial duct that connects the pulmonary artery to the descending aorta; this opening normally closes within 24 hours of birth. [NIH] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]
Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Pathologies: The study of abnormality, especially the study of diseases. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Patient Care Team: Care of patients by a multidisciplinary team usually organized under the leadership of a physician; each member of the team has specific responsibilities and the whole team contributes to the care of the patient. [NIH] Patient Compliance: Voluntary cooperation of the patient in following a prescribed regimen. [NIH] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]
Patient Selection: Criteria and standards used for the determination of the appropriateness of the inclusion of patients with specific conditions in proposed treatment plans and the criteria used for the inclusion of subjects in various clinical trials and other research protocols. [NIH] Pelvic: Pertaining to the pelvis. [EU] 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] Peptide Chain Elongation: The process whereby an amino acid is joined through a substituted amide linkage to a chain of peptides. [NIH]
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Perception: The ability quickly and accurately to recognize similarities and differences among presented objects, whether these be pairs of words, pairs of number series, or multiple sets of these or other symbols such as geometric figures. [NIH] Perfusion: Bathing an organ or tissue with a fluid. In regional perfusion, a specific area of the body (usually an arm or a leg) receives high doses of anticancer drugs through a blood vessel. Such a procedure is performed to treat cancer that has not spread. [NIH] 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] Periodontal disease: Disease involving the supporting structures of the teeth (as the gums and periodontal membranes). [NIH] Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] Peripheral Neuropathy: Nerve damage, usually affecting the feet and legs; causing pain, numbness, or a tingling feeling. Also called "somatic neuropathy" or "distal sensory polyneuropathy." [NIH] Peripheral Vascular Disease: Disease in the large blood vessels of the arms, legs, and feet. People who have had diabetes for a long time may get this because major blood vessels in their arms, legs, and feet are blocked and these limbs do not receive enough blood. The signs of PVD are aching pains in the arms, legs, and feet (especially when walking) and foot sores that heal slowly. Although people with diabetes cannot always avoid PVD, doctors say they have a better chance of avoiding it if they take good care of their feet, do not smoke, and keep both their blood pressure and diabetes under good control. [NIH] Peritoneal: Having to do with the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Peritoneal Cavity: The space enclosed by the peritoneum. It is divided into two portions, the greater sac and the lesser sac or omental bursa, which lies behind the stomach. The two sacs are connected by the foramen of Winslow, or epiploic foramen. [NIH] Perspiration: Sweating; the functional secretion of sweat. [EU] Pesticides: Chemicals used to destroy pests of any sort. The concept includes fungicides (industrial fungicides), insecticides, rodenticides, etc. [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] Pharmacist: A person trained to prepare and distribute medicines and to give information about them. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Pharmacotherapy: A regimen of using appetite suppressant medications to manage obesity by decreasing appetite or increasing the feeling of satiety. These medications decrease appetite by increasing serotonin or catecholamine—two brain chemicals that affect mood
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and appetite. [NIH] Pharynx: The hollow tube about 5 inches long that starts behind the nose and ends at the top of the trachea (windpipe) and esophagus (the tube that goes to the stomach). [NIH] Phencyclidine: A hallucinogen formerly used as a veterinary anesthetic, and briefly as a general anesthetic for humans. Phencyclidine is similar to ketamine in structure and in many of its effects. Like ketamine, it can produce a dissociative state. It exerts its pharmacological action through inhibition of NMDA receptors (receptors, N-methyl-Daspartate). As a drug of abuse, it is known as PCP and Angel Dust. [NIH] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phobia: A persistent, irrational, intense fear of a specific object, activity, or situation (the phobic stimulus), fear that is recognized as being excessive or unreasonable by the individual himself. When a phobia is a significant source of distress or interferes with social functioning, it is considered a mental disorder; phobic disorder (or neurosis). In DSM III phobic disorders are subclassified as agoraphobia, social phobias, and simple phobias. Used as a word termination denoting irrational fear of or aversion to the subject indicated by the stem to which it is affixed. [EU] Phobic Disorders: Anxiety disorders in which the essential feature is persistent and irrational fear of a specific object, activity, or situation that the individual feels compelled to avoid. The individual recognizes the fear as excessive or unreasonable. [NIH] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Phosphorylate: Attached to a phosphate group. [NIH] Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. [NIH] Physical Examination: Systematic and thorough inspection of the patient for physical signs of disease or abnormality. [NIH] Physical Fitness: A state of well-being in which performance is optimal, often as a result of physical conditioning which may be prescribed for disease therapy. [NIH] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]
Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Pigment: A substance that gives color to tissue. Pigments are responsible for the color of skin, eyes, and hair. [NIH]
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Piloerection: Involuntary erection or bristling of hairs. [NIH] Pilot study: The initial study examining a new method or treatment. [NIH] Piperidines: A family of hexahydropyridines. Piperidine itself is found in the pepper plant as the alkaloid piperine. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [NIH] Placenta: A highly vascular fetal organ through which the fetus absorbs oxygen and other nutrients and excretes carbon dioxide and other wastes. It begins to form about the eighth day of gestation when the blastocyst adheres to the decidua. [NIH] Placental Insufficiency: Failure of the placenta to deliver an adequate supply of nutrients and oxygen to the fetus. [NIH] Placental tissue: The tissue intervening between fetal blood and maternal blood in the placenta; it acts as a selective membrane regulating the passage of substances from the maternal to the fetal blood. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plaque: A clear zone in a bacterial culture grown on an agar plate caused by localized destruction of bacterial cells by a bacteriophage. The concentration of infective virus in a fluid can be estimated by applying the fluid to a culture and counting the number of. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasma protein: One of the hundreds of different proteins present in blood plasma, including carrier proteins ( such albumin, transferrin, and haptoglobin), fibrinogen and other coagulation factors, complement components, immunoglobulins, enzyme inhibitors, precursors of substances such as angiotension and bradykinin, and many other types of proteins. [EU] Plasma Volume: Volume of plasma in the circulation. It is usually measured by indicator dilution techniques. [NIH] Plasticity: In an individual or a population, the capacity for adaptation: a) through gene changes (genetic plasticity) or b) through internal physiological modifications in response to changes of environment (physiological plasticity). [NIH] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Platinum: Platinum. A heavy, soft, whitish metal, resembling tin, atomic number 78, atomic weight 195.09, symbol Pt. (From Dorland, 28th ed) It is used in manufacturing equipment
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for laboratory and industrial use. It occurs as a black powder (platinum black) and as a spongy substance (spongy platinum) and may have been known in Pliny's time as "alutiae". [NIH]
Pleura: The thin serous membrane enveloping the lungs and lining the thoracic cavity. [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Polycystic: An inherited disorder characterized by many grape-like clusters of fluid-filled cysts that make both kidneys larger over time. These cysts take over and destroy working kidney tissue. PKD may cause chronic renal failure and end-stage renal disease. [NIH] Polyethylene: A vinyl polymer made from ethylene. It can be branched or linear. Branched or low-density polyethylene is tough and pliable but not to the same degree as linear polyethylene. Linear or high-density polyethylene has a greater hardness and tensile strength. Polyethylene is used in a variety of products, including implants and prostheses. [NIH]
Polymerase: An enzyme which catalyses the synthesis of DNA using a single DNA strand as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH] Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships. [NIH] Polymers: Compounds formed by the joining of smaller, usually repeating, units linked by covalent bonds. These compounds often form large macromolecules (e.g., polypeptides, proteins, plastics). [NIH] 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] Pontine: A brain region involved in the detection and processing of taste. [NIH] Portal Vein: A short thick vein formed by union of the superior mesenteric vein and the splenic vein. [NIH] Portosystemic Shunt: An operation to create an opening between the portal vein and other veins around the liver. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postmenopausal: Refers to the time after menopause. Menopause is the time in a woman's life when menstrual periods stop permanently; also called "change of life." [NIH] Postnatal: Occurring after birth, with reference to the newborn. [EU] Postoperative: After surgery. [NIH] Postprandial: Occurring after dinner, or after a meal; postcibal. [EU] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Post-translational: The cleavage of signal sequence that directs the passage of the protein
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through a cell or organelle membrane. [NIH] Post-traumatic: Occurring as a result of or after injury. [EU] Post-traumatic stress disorder: A psychological disorder that develops in some individuals after a major traumatic experience such as war, rape, domestic violence, or accident. [NIH] Postural: Pertaining to posture or position. [EU] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Potassium Channels: Cell membrane glycoproteins selective for potassium ions. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Praseodymium: Praseodymium. An element of the rare earth family of metals. It has the atomic symbol Pr, atomic number 59, and atomic weight 140.91. [NIH] Preclinical: Before a disease becomes clinically recognizable. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Predisposition: A latent susceptibility to disease which may be activated under certain conditions, as by stress. [EU] Pregnancy in Diabetics: Previously diagnosed diabetics that become pregnant. This does not include either symptomatic diabetes or impaired glucose tolerance induced by pregnancy but resolved at the end of pregnancy (diabetes, gestational). [NIH] Pregnancy Outcome: Results of conception and ensuing pregnancy, including live birth, stillbirth, spontaneous abortion, induced abortion. The outcome may follow natural or artificial insemination or any of the various reproduction techniques, such as embryo transfer or fertilization in vitro. [NIH] Pregnancy Tests: Tests to determine whether or not an individual is pregnant. [NIH] Pressoreceptors: Receptors in the vascular system, particularly the aorta and carotid sinus, which are sensitive to stretch of the vessel walls. [NIH] Presynaptic: Situated proximal to a synapse, or occurring before the synapse is crossed. [EU] Presynaptic Terminals: The distal terminations of axons which are specialized for the release of neurotransmitters. Also included are varicosities along the course of axons which have similar specializations and also release transmitters. Presynaptic terminals in both the central and peripheral nervous systems are included. [NIH] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] 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
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exploring or sounding body cavities. [NIH] Problem Solving: A learning situation involving more than one alternative from which a selection is made in order to attain a specific goal. [NIH] Procaine: A local anesthetic of the ester type that has a slow onset and a short duration of action. It is mainly used for infiltration anesthesia, peripheral nerve block, and spinal block. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1016). [NIH] 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 antiovulatory agent when administered on days 5-25 of the menstrual cycle. [NIH] Prognostic factor: A situation or condition, or a characteristic of a patient, that can be used to estimate the chance of recovery from a disease, or the chance of the disease recurring (coming back). [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] 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] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH] Proline: A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Promotor: In an operon, a nucleotide sequence located at the operator end which contains all the signals for the correct initiation of genetic transcription by the RNA polymerase holoenzyme and determines the maximal rate of RNA synthesis. [NIH] 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 study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] Prostaglandin: Any of a group of components derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway that are extremely potent mediators of a diverse group of physiologic processes. The abbreviation for prostaglandin is PG; specific compounds are designated by adding one of the letters A through I to indicate the type of substituents found on the hydrocarbon skeleton and a subscript (1, 2 or 3) to indicate the number of double bonds in the hydrocarbon skeleton e.g., PGE2. The
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predominant naturally occurring prostaglandins all have two double bonds and are synthesized from arachidonic acid (5,8,11,14-eicosatetraenoic acid) by the pathway shown in the illustration. The 1 series and 3 series are produced by the same pathway with fatty acids having one fewer double bond (8,11,14-eicosatrienoic acid or one more double bond (5,8,11,14,17-eicosapentaenoic acid) than arachidonic acid. The subscript a or ß indicates the configuration at C-9 (a denotes a substituent below the plane of the ring, ß, above the plane). The naturally occurring PGF's have the a configuration, e.g., PGF2a. All of the prostaglandins act by binding to specific cell-surface receptors causing an increase in the level of the intracellular second messenger cyclic AMP (and in some cases cyclic GMP also). The effect produced by the cyclic AMP increase depends on the specific cell type. In some cases there is also a positive feedback effect. Increased cyclic AMP increases prostaglandin synthesis leading to further increases in cyclic AMP. [EU] Prostaglandins A: (13E,15S)-15-Hydroxy-9-oxoprosta-10,13-dien-1-oic acid (PGA(1)); (5Z,13E,15S)-15-hydroxy-9-oxoprosta-5,10,13-trien-1-oic acid (PGA(2)); (5Z,13E,15S,17Z)-15hydroxy-9-oxoprosta-5,10,13,17-tetraen-1-oic acid (PGA(3)). A group of naturally occurring secondary prostaglandins derived from PGE. PGA(1) and PGA(2) as well as their 19hydroxy derivatives are found in many organs and tissues. [NIH] Prostaglandins F: (9 alpha,11 alpha,13E,15S)-9,11,15-Trihydroxyprost-13-en-1-oic acid (PGF(1 alpha)); (5Z,9 alpha,11,alpha,13E,15S)-9,11,15-trihydroxyprosta-5,13-dien-1-oic acid (PGF(2 alpha)); (5Z,9 alpha,11 alpha,13E,15S,17Z)-9,11,15-trihydroxyprosta-5,13,17-trien-1oic acid (PGF(3 alpha)). A family of prostaglandins that includes three of the six naturally occurring prostaglandins. All naturally occurring PGF have an alpha configuration at the 9carbon position. They stimulate uterine and bronchial smooth muscle and are often used as oxytocics. [NIH] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protective Agents: Synthetic or natural substances which are given to prevent a disease or disorder or are used in the process of treating a disease or injury due to a poisonous agent. [NIH]
Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein 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] Protein Transport: The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Proteinuria: The presence of protein in the urine, indicating that the kidneys are not working properly. [NIH] Proteoglycans: Glycoproteins which have a very high polysaccharide content. [NIH] Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that
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promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Protozoa: A subkingdom consisting of unicellular organisms that are the simplest in the animal kingdom. Most are free living. They range in size from submicroscopic to macroscopic. Protozoa are divided into seven phyla: Sarcomastigophora, Labyrinthomorpha, Apicomplexa, Microspora, Ascetospora, Myxozoa, and Ciliophora. [NIH] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Psychiatric: Pertaining to or within the purview of psychiatry. [EU] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Psychology: The science dealing with the study of mental processes and behavior in man and animals. [NIH] Psychomotor: Pertaining to motor effects of cerebral or psychic activity. [EU] Psychosis: A mental disorder characterized by gross impairment in reality testing as evidenced by delusions, hallucinations, markedly incoherent speech, or disorganized and agitated behaviour without apparent awareness on the part of the patient of the incomprehensibility of his behaviour; the term is also used in a more general sense to refer to mental disorders in which mental functioning is sufficiently impaired as to interfere grossly with the patient's capacity to meet the ordinary demands of life. Historically, the term has been applied to many conditions, e.g. manic-depressive psychosis, that were first described in psychotic patients, although many patients with the disorder are not judged psychotic. [EU] Psychotherapy: A generic term for the treatment of mental illness or emotional disturbances primarily by verbal or nonverbal communication. [NIH] 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]
Pulmonary: Relating to the lungs. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] Pulmonary Edema: An accumulation of an excessive amount of watery fluid in the lungs,
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may be caused by acute exposure to dangerous concentrations of irritant gasses. [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] Purulent: Consisting of or containing pus; associated with the formation of or caused by pus. [EU] Putrefaction: The process of decomposition of animal and vegetable matter by living organisms. [NIH] Pylorus: The opening in a vertebrate from the stomach into the intestine. [EU] Pyridoxal: 3-Hydroxy-5-(hydroxymethyl)-2-methyl-4- pyridinecarboxaldehyde. [NIH] Pyridoxal Phosphate: 3-Hydroxy-2-methyl-5-((phosphonooxy)methyl)-4pyridinecarboxaldehyde. An enzyme co-factor vitamin. [NIH] Pyruvate Kinase: ATP:pyruvate 2-O-phosphotransferase. A phosphotransferase that catalyzes reversibly the phosphorylation of pyruvate to phosphoenolpyruvate in the presence of ATP. It has four isozymes (L, R, M1, and M2). Deficiency of the enzyme results in hemolytic anemia. EC 2.7.1.40. [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] Quinolinic: It is produced by immune cells and slowly infiltrates the brain tissues after an injury. [NIH] Quinolinic Acid: 2,3-Pyridinedicarboxylic acid. A metabolite of tryptophan with a possible role in neurodegenerative disorders. Elevated CSF levels of quinolinic acid are significantly correlated with the severity of neuropsychological deficits in patients who have AIDS. [NIH] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH] Radioactive: Giving off radiation. [NIH] 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] Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH] Radiotherapy: The use of ionizing radiation to treat malignant neoplasms and other benign conditions. The most common forms of ionizing radiation used as therapy are x-rays, gamma rays, and electrons. A special form of radiotherapy, targeted radiotherapy, links a
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cytotoxic radionuclide to a molecule that targets the tumor. When this molecule is an antibody or other immunologic molecule, the technique is called radioimmunotherapy. [NIH] 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] Rape: Unlawful sexual intercourse without consent of the victim. [NIH] Reaction Time: The time from the onset of a stimulus until the organism responds. [NIH] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] Reality Testing: The individual's objective evaluation of the external world and the ability to differentiate adequately between it and the internal world; considered to be a primary ego function. [NIH] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Receptors, Serotonin: Cell-surface proteins that bind serotonin and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Red Nucleus: A pinkish-yellow portion of the midbrain situated in the rostral mesencephalic tegmentum. It receives a large projection from the contralateral half of the cerebellum via the superior cerebellar peduncle and a projection from the ipsilateral motor cortex. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Reflux: The term used when liquid backs up into the esophagus from the stomach. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Regurgitation: A backward flowing, as the casting up of undigested food, or the backward flowing of blood into the heart, or between the chambers of the heart when a valve is incompetent. [EU] Rehydration: The restoration of water or of fluid content to a body or to substance which has become dehydrated. [EU] Reliability: Used technically, in a statistical sense, of consistency of a test with itself, i. e. the extent to which we can assume that it will yield the same result if repeated a second time. [NIH]
Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Renal failure: Progressive renal insufficiency and uremia, due to irreversible and progressive renal glomerular tubular or interstitial disease. [NIH] Reperfusion: Restoration of blood supply to tissue which is ischemic due to decrease in normal blood supply. The decrease may result from any source including atherosclerotic
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obstruction, narrowing of the artery, or surgical clamping. It is primarily a procedure for treating infarction or other ischemia, by enabling viable ischemic tissue to recover, thus limiting further necrosis. However, it is thought that reperfusion can itself further damage the ischemic tissue, causing reperfusion injury. [NIH] Reperfusion Injury: Functional, metabolic, or structural changes, including necrosis, in ischemic tissues thought to result from reperfusion to ischemic areas of the tissue. The most common instance is myocardial reperfusion injury. [NIH] Reproduction Techniques: Methods pertaining to the generation of new individuals. [NIH] Research Design: A plan for collecting and utilizing data so that desired information can be obtained with sufficient precision or so that an hypothesis can be tested properly. [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] Respiratory Therapy: Care of patients with deficiencies and abnormalities associated with the cardiopulmonary system. It includes the therapeutic use of medical gases and their administrative apparatus, environmental control systems, humidification, aerosols, ventilatory support, bronchopulmonary drainage and exercise, respiratory rehabilitation, assistance with cardiopulmonary resuscitation, and maintenance of natural, artificial, and mechanical airways. [NIH] Response Elements: Nucleotide sequences, usually upstream, which are recognized by specific regulatory transcription factors, thereby causing gene response to various regulatory agents. These elements may be found in both promotor and enhancer regions. [NIH]
Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [NIH] Resuscitation: The restoration to life or consciousness of one apparently dead; it includes such measures as artificial respiration and cardiac massage. [EU] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] Retinal: 1. Pertaining to the retina. 2. The aldehyde of retinol, derived by the oxidative enzymatic splitting of absorbed dietary carotene, and having vitamin A activity. In the retina, retinal combines with opsins to form visual pigments. One isomer, 11-cis retinal combines with opsin in the rods (scotopsin) to form rhodopsin, or visual purple. Another, all-trans retinal (trans-r.); visual yellow; xanthopsin) results from the bleaching of rhodopsin by light, in which the 11-cis form is converted to the all-trans form. Retinal also combines with opsins in the cones (photopsins) to form the three pigments responsible for colour vision. Called also retinal, and retinene1. [EU] Retinitis: Inflammation of the retina. It is rarely limited to the retina, but is commonly associated with diseases of the choroid (chorioretinitis) and of the optic nerve (neuroretinitis). The disease may be confined to one eye, but since it is generally dependent on a constitutional factor, it is almost always bilateral. It may be acute in course, but as a rule
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it lasts many weeks or even several months. [NIH] Retinitis Pigmentosa: Hereditary, progressive degeneration of the neuroepithelium of the retina characterized by night blindness and progressive contraction of the visual field. [NIH] Retinoblastoma: An eye cancer that most often occurs in children younger than 5 years. It occurs in hereditary and nonhereditary (sporadic) forms. [NIH] Retinoblastoma Protein: Product of the retinoblastoma tumor suppressor gene. It is a nuclear phosphoprotein hypothesized to normally act as an inhibitor of cell proliferation. Rb protein is absent in retinoblastoma cell lines. It also has been shown to form complexes with the adenovirus E1A protein, the SV40 T antigen, and the human papilloma virus E7 protein. [NIH]
Retinoid: Vitamin A or a vitamin A-like compound. [NIH] Retinol: Vitamin A. It is essential for proper vision and healthy skin and mucous membranes. Retinol is being studied for cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Retinopathy: 1. Retinitis (= inflammation of the retina). 2. Retinosis (= degenerative, noninflammatory condition of the retina). [EU] Retrograde: 1. Moving backward or against the usual direction of flow. 2. Degenerating, deteriorating, or catabolic. [EU] Retrospective: Looking back at events that have already taken place. [NIH] Retrospective study: A study that looks backward in time, usually using medical records and interviews with patients who already have or had a disease. [NIH] Retroviral vector: RNA from a virus that is used to insert genetic material into cells. [NIH] Retrovirus: A member of a group of RNA viruses, the RNA of which is copied during viral replication into DNA by reverse transcriptase. The viral DNA is then able to be integrated into the host chromosomal DNA. [NIH] Rhabdomyolysis: Necrosis or disintegration of skeletal muscle often followed by myoglobinuria. [NIH] Rheumatism: A group of disorders marked by inflammation or pain in the connective tissue structures of the body. These structures include bone, cartilage, and fat. [NIH] Rheumatoid: Resembling rheumatism. [EU] Rheumatoid arthritis: A form of arthritis, the cause of which is unknown, although infection, hypersensitivity, hormone imbalance and psychologic stress have been suggested as possible causes. [NIH] Rhythm Method: A contraceptive method whereby abstinence is practiced a few days before and after the estimated day of ovulation. [NIH] Ribose: A pentose active in biological systems usually in its D-form. [NIH] Ribosome: A granule of protein and RNA, synthesized in the nucleolus and found in the cytoplasm of cells. Ribosomes are the main sites of protein synthesis. Messenger RNA attaches to them and there receives molecules of transfer RNA bearing amino acids. [NIH] Rigidity: Stiffness or inflexibility, chiefly that which is abnormal or morbid; rigor. [EU] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Rod: A reception for vision, located in the retina. [NIH] Rodenticides: Substances used to destroy or inhibit the action of rats, mice, or other rodents. [NIH]
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Rosiglitazone: A drug taken to help reduce the amount of sugar in the blood. Rosiglitazone helps make insulin more effective and improves regulation of blood sugar. It belongs to the family of drugs called thiazolidinediones. [NIH] Salicylate: Non-steroidal anti-inflammatory drugs. [NIH] Salicylic: A tuberculosis drug. [NIH] Salicylic Acids: Derivatives and salts of salicylic acid. [NIH] Saline: A solution of salt and water. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] 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] Satellite: Applied to a vein which closely accompanies an artery for some distance; in cytogenetics, a chromosomal agent separated by a secondary constriction from the main body of the chromosome. [NIH] Satiation: Full gratification of a need or desire followed by a state of relative insensitivity to that particular need or desire. [NIH] Schizoid: Having qualities resembling those found in greater degree in schizophrenics; a person of schizoid personality. [NIH] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [NIH] Schizotypal Personality Disorder: A personality disorder in which there are oddities of thought (magical thinking, paranoid ideation, suspiciousness), perception (illusions, depersonalization), speech (digressive, vague, overelaborate), and behavior (inappropriate affect in social interactions, frequently social isolation) that are not severe enough to characterize schizophrenia. [NIH] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Second Messenger Systems: Systems in which an intracellular signal is generated in response to an intercellular primary messenger such as a hormone or neurotransmitter. They are intermediate signals in cellular processes such as metabolism, secretion, contraction, phototransduction, and cell growth. Examples of second messenger systems are the adenyl cyclase-cyclic AMP system, the phosphatidylinositol diphosphate-inositol triphosphate system, and the cyclic GMP system. [NIH] Secondary tumor: Cancer that has spread from the organ in which it first appeared to another organ. For example, breast cancer cells may spread (metastasize) to the lungs and cause the growth of a new tumor. When this happens, the disease is called metastatic breast cancer, and the tumor in the lungs is called a secondary tumor. Also called secondary cancer. [NIH] 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]
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Secretory: Secreting; relating to or influencing secretion or the secretions. [NIH] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH] Self Administration: Administration of a drug or chemical by the individual under the direction of a physician. It includes administration clinically or experimentally, by human or animal. [NIH] Self Care: Performance of activities or tasks traditionally performed by professional health care providers. The concept includes care of oneself or one's family and friends. [NIH] Sella: A deep depression in the shape of a Turkish saddle in the upper surface of the body of the sphenoid bone in the deepest part of which is lodged the hypophysis cerebri. [NIH] Semen: The thick, yellowish-white, viscid fluid secretion of male reproductive organs discharged upon ejaculation. In addition to reproductive organ secretions, it contains spermatozoa and their nutrient plasma. [NIH] Semicircular canal: Three long canals of the bony labyrinth of the ear, forming loops and opening into the vestibule by five openings. [NIH] Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [NIH] Sensor: A device designed to respond to physical stimuli such as temperature, light, magnetism or movement and transmit resulting impulses for interpretation, recording, movement, or operating control. [NIH] Sepsis: The presence of bacteria in the bloodstream. [NIH] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (receptors, serotonin) explain the broad physiological actions and distribution of this biochemical mediator. [NIH] Serous: Having to do with serum, the clear liquid part of blood. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Sex Characteristics: Those characteristics that distinguish one sex from the other. The primary sex characteristics are the ovaries and testes and their related hormones. Secondary sex characteristics are those which are masculine or feminine but not directly related to reproduction. [NIH] Sex Determination: The biological characteristics which distinguish human beings as female or male. [NIH] Sexually Transmitted Diseases: Diseases due to or propagated by sexual contact. [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
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the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Skin Care: Maintenance of the hygienic state of the skin under optimal conditions of cleanliness and comfort. Effective in skin care are proper washing, bathing, cleansing, and the use of soaps, detergents, oils, etc. In various disease states, therapeutic and protective solutions and ointments are useful. The care of the skin is particularly important in various occupations, in exposure to sunlight, in neonates, and in decubitus ulcer. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Sleep apnea: A serious, potentially life-threatening breathing disorder characterized by repeated cessation of breathing due to either collapse of the upper airway during sleep or absence of respiratory effort. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]
Soaps: Sodium or potassium salts of long chain fatty acids. These detergent substances are obtained by boiling natural oils or fats with caustic alkali. Sodium soaps are harder and are used as topical anti-infectives and vehicles in pills and liniments; potassium soaps are soft, used as vehicles for ointments and also as topical antimicrobials. [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] Sodium Channels: Cell membrane glycoproteins selective for sodium ions. Fast sodium
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current is associated with the action potential in neural membranes. [NIH] Sodium salicylate: A drug that belongs to the family of drugs called nonsteroidal antiinflammatory drugs. Sodium salicylate may be tolerated by people who are sensitive to aspirin. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solid tumor: Cancer of body tissues other than blood, bone marrow, or the lymphatic system. [NIH] Solitary Nucleus: Gray matter located in the dorsomedial part of the medulla oblongata associated with the solitary tract. The solitary nucleus receives inputs from most organ systems including the terminations of the facial, glossopharyngeal, and vagus nerves. It is a major coordinator of autonomic nervous system regulation of cardiovascular, respiratory, gustatory, gastrointestinal, and chemoreceptive aspects of homeostasis. The solitary nucleus is also notable for the large number of neurotransmitters which are found therein. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] 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] Somatotropin: A small peptide hormone released by the anterior pituitary under hypothalamic control. Somatotropin, or growth hormone, stimulates mitosis, cell growth, and, for some cell types, differentiation in many tissues of the body. It has profound effects on many aspects of gene expression and metabolism. [NIH] Sorbitol: A polyhydric alcohol with about half the sweetness of sucrose. Sorbitol occurs naturally and is also produced synthetically from glucose. It was formerly used as a diuretic and may still be used as a laxative and in irrigating solutions for some surgical procedures. It is also used in many manufacturing processes, as a pharmaceutical aid, and in several research applications. [NIH] Spasm: An involuntary contraction of a muscle or group of muscles. Spasms may involve skeletal muscle or smooth muscle. [NIH] Spastic: 1. Of the nature of or characterized by spasms. 2. Hypertonic, so that the muscles are stiff and the movements awkward. 3. A person exhibiting spasticity, such as occurs in spastic paralysis or in cerebral palsy. [EU] Spasticity: A state of hypertonicity, or increase over the normal tone of a muscle, with heightened deep tendon reflexes. [EU] Spatial disorientation: Loss of orientation in space where person does not know which way is up. [NIH] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU]
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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] Spermidine: A polyamine formed from putrescine. It is found in almost all tissues in association with nucleic acids. It is found as a cation at all pH values, and is thought to help stabilize some membranes and nucleic acid structures. It is a precursor of spermine. [NIH] Spermine: A biogenic polyamine formed from spermidine. It is found in a wide variety of organisms and tissues and is an essential growth factor in some bacteria. It is found as a polycation at all pH values. Spermine is associated with nucleic acids, particularly in viruses, and is thought to stabilize the helical structure. [NIH] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spinal Cord Ischemia: Reduced blood flow to the spinal cord which is supplied by the anterior spinal artery and the paired posterior spinal arteries. This condition may be associated with arteriosclerosis, trauma, emboli, diseases of the aorta, and other disorders. Prolonged ischemia may lead to infarction of spinal cord tissue. [NIH] Spinal Nerves: The 31 paired peripheral nerves formed by the union of the dorsal and ventral spinal roots from each spinal cord segment. The spinal nerve plexuses and the spinal roots are also included. [NIH] Spleen: An organ that is part of the lymphatic system. The spleen produces lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side of the abdomen near the stomach. [NIH] Splenectomy: An operation to remove the spleen. [NIH] Spontaneous Abortion: The non-induced birth of an embryo or of fetus prior to the stage of viability at about 20 weeks of gestation. [NIH] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Sprains and Strains: A collective term for muscle and ligament injuries without dislocation or fracture. A sprain is a joint injury in which some of the fibers of a supporting ligament are ruptured but the continuity of the ligament remains intact. A strain is an overstretching or overexertion of some part of the musculature. [NIH] Standard therapy: A currently accepted and widely used treatment for a certain type of cancer, based on the results of past research. [NIH] Status Epilepticus: Repeated and prolonged epileptic seizures without recovery of consciousness between attacks. [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] 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]
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Sterilization: The destroying of all forms of life, especially microorganisms, by heat, chemical, or other means. [NIH] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Stillbirth: The birth of a dead fetus or baby. [NIH] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]
Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stomatitis: Inflammation of the oral mucosa, due to local or systemic factors which may involve the buccal and labial mucosa, palate, tongue, floor of the mouth, and the gingivae. [EU]
Stool: The waste matter discharged in a bowel movement; feces. [NIH] Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Structure-Activity Relationship: The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Other factors contributing to structure-activity relationship include chemical reactivity, electronic effects, resonance, and inductive effects. [NIH] Strychnine: An alkaloid found in the seeds of nux vomica. It is a competitive antagonist at glycine receptors and thus a convulsant. It has been used as an analeptic, in the treatment of nonketotic hyperglycinemia and sleep apnea, and as a rat poison. [NIH] Stupor: Partial or nearly complete unconsciousness, manifested by the subject's responding only to vigorous stimulation. Also, in psychiatry, a disorder marked by reduced responsiveness. [EU] Subacute: Somewhat acute; between acute and chronic. [EU] Subarachnoid: Situated or occurring between the arachnoid and the pia mater. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subcutaneous: Beneath the skin. [NIH] Subiculum: A region of the hippocampus that projects to other areas of the brain. [NIH] Subspecies: A category intermediate in rank between species and variety, based on a
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smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]
Substrate: A substance upon which an enzyme acts. [EU] Sudden death: Cardiac arrest caused by an irregular heartbeat. The term "death" is somewhat misleading, because some patients survive. [NIH] Sulfur: An element that is a member of the chalcogen family. It has an atomic symbol S, atomic number 16, and atomic weight 32.066. It is found in the amino acids cysteine and methionine. [NIH] Supplementation: Adding nutrients to the diet. [NIH] Support group: A group of people with similar disease who meet to discuss how better to cope with their cancer and treatment. [NIH] Suppositories: A small cone-shaped medicament having cocoa butter or gelatin at its basis and usually intended for the treatment of local conditions in the rectum. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Survival Analysis: A class of statistical procedures for estimating the survival function (function of time, starting with a population 100% well at a given time and providing the percentage of the population still well at later times). The survival analysis is then used for making inferences about the effects of treatments, prognostic factors, exposures, and other covariates on the function. [NIH] Sweat: The fluid excreted by the sweat glands. It consists of water containing sodium 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] Symphysis: A secondary cartilaginous joint. [NIH] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Symptomatology: 1. That branch of medicine with treats of symptoms; the systematic discussion of symptoms. 2. The combined symptoms of a disease. [EU] Synapses: Specialized junctions at which a neuron communicates with a target cell. At classical synapses, a neuron's presynaptic terminal releases a chemical transmitter stored in synaptic vesicles which diffuses across a narrow synaptic cleft and activates receptors on the postsynaptic membrane of the target cell. The target may be a dendrite, cell body, or axon of another neuron, or a specialized region of a muscle or secretory cell. Neurons may also communicate through direct electrical connections which are sometimes called electrical synapses; these are not included here but rather in gap junctions. [NIH]
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Synapsis: The pairing between homologous chromosomes of maternal and paternal origin during the prophase of meiosis, leading to the formation of gametes. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Synaptic Transmission: The communication from a neuron to a target (neuron, muscle, or secretory cell) across a synapse. In chemical synaptic transmission, the presynaptic neuron releases a neurotransmitter that diffuses across the synaptic cleft and binds to specific synaptic receptors. These activated receptors modulate ion channels and/or secondmessenger systems to influence the postsynaptic cell. Electrical transmission is less common in the nervous system, and, as in other tissues, is mediated by gap junctions. [NIH] Synaptic Vesicles: Membrane-bound compartments which contain transmitter molecules. Synaptic vesicles are concentrated at presynaptic terminals. They actively sequester transmitter molecules from the cytoplasm. In at least some synapses, transmitter release occurs by fusion of these vesicles with the presynaptic membrane, followed by exocytosis of their contents. [NIH] Synchrony: The normal physiologic sequencing of atrial and ventricular activation and contraction. [NIH] Syncope: A temporary suspension of consciousness due to generalized cerebral schemia, a faint or swoon. [EU] Systemic: Affecting the entire body. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Tachycardia: Excessive rapidity in the action of the heart, usually with a heart rate above 100 beats per minute. [NIH] Tardive: Marked by lateness, late; said of a disease in which the characteristic lesion is late in appearing. [EU] Telangiectasia: The permanent enlargement of blood vessels, causing redness in the skin or mucous membranes. [NIH] Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the skull, and containing the organs of hearing. [NIH] Temporal Lobe: Lower lateral part of the cerebral hemisphere. [NIH] Teratoma: A type of germ cell tumor that may contain several different types of tissue, such as hair, muscle, and bone. Teratomas occur most often in the ovaries in women, the testicles in men, and the tailbone in children. Not all teratomas are malignant. [NIH] Testicles: The two egg-shaped glands found inside the scrotum. They produce sperm and male hormones. Also called testes. [NIH] Tetani: Causal agent of tetanus. [NIH] Tetanic: Having the characteristics of, or relating to tetanus. [NIH] Tetanus: A disease caused by tetanospasmin, a powerful protein toxin produced by Clostridium tetani. Tetanus usually occurs after an acute injury, such as a puncture wound or laceration. Generalized tetanus, the most common form, is characterized by tetanic muscular contractions and hyperreflexia. Localized tetanus presents itself as a mild condition with manifestations restricted to muscles near the wound. It may progress to the
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generalized form. [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] Thalamic: Cell that reaches the lateral nucleus of amygdala. [NIH] Thalamic Diseases: Disorders of the centrally located thalamus, which integrates a wide range of cortical and subcortical information. Manifestations include sensory loss, movement disorders; ataxia, pain syndromes, visual disorders, a variety of neuropsychological conditions, and coma. Relatively common etiologies include cerebrovascular disorders; craniocerebral trauma; brain neoplasms; brain hypoxia; intracranial hemorrhages; and infectious processes. [NIH] Thalamus: Paired bodies containing mostly gray substance and forming part of the lateral wall of the third ventricle of the brain. The thalamus represents the major portion of the diencephalon and is commonly divided into cellular aggregates known as nuclear groups. [NIH]
Theophylline: Alkaloid obtained from Thea sinensis (tea) and others. It stimulates the heart and central nervous system, dilates bronchi and blood vessels, and causes diuresis. The drug is used mainly in bronchial asthma and for myocardial stimulation. Among its more prominent cellular effects are inhibition of cyclic nucleotide phosphodiesterases and antagonism of adenosine receptors. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thermal: Pertaining to or characterized by heat. [EU] Third Ventricle: A narrow cleft inferior to the corpus callosum, within the diencephalon, between the paired thalami. Its floor is formed by the hypothalamus, its anterior wall by the lamina terminalis, and its roof by ependyma. It communicates with the fourth ventricle by the cerebral aqueduct, and with the lateral ventricles by the interventricular foramina. [NIH] Thoracic: Having to do with the chest. [NIH] Thorax: A part of the trunk between the neck and the abdomen; the chest. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thromboembolism: Obstruction of a vessel by a blood clot that has been transported from a distant site by the blood stream. [NIH] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]
Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thrombus: An aggregation of blood factors, primarily platelets and fibrin with entrapment of cellular elements, frequently causing vascular obstruction at the point of its formation. Some authorities thus differentiate thrombus formation from simple coagulation or clot formation. [EU] Thymus: An organ that is part of the lymphatic system, in which T lymphocytes grow and
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multiply. The thymus is in the chest behind the breastbone. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Thyroid Gland: A highly vascular endocrine gland consisting of two lobes, one on either side of the trachea, joined by a narrow isthmus; it produces the thyroid hormones which are concerned in regulating the metabolic rate of the body. [NIH] Thyroid Hormones: Hormones secreted by the thyroid gland. [NIH] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH] Tin: A trace element that is required in bone formation. It has the atomic symbol Sn, atomic number 50, and atomic weight 118.71. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tolazamide: A sulphonylurea hypoglycemic agent with actions and uses similar to those of chlorpropamide. [NIH] Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU] 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] Total pancreatectomy: Surgery to remove the entire pancreas. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [NIH] Toxoid: The material resulting from the treatment of toxin in such a way that the toxic properties are inactivated whilst the antigenic potency remains intact. [NIH] Trace element: Substance or element essential to plant or animal life, but present in extremely small amounts. [NIH] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Traction: The act of pulling. [NIH] 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
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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] Transient Ischemic Attacks: Focal neurologic abnormalities of sudden onset and brief duration that reflect dysfunction in the distribution of the internal carotid-middle cerebral or the vertebrobasilar arterial system. [NIH] Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Translocation: The movement of material in solution inside the body of the plant. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Tremor: Cyclical movement of a body part that can represent either a physiologic process or a manifestation of disease. Intention or action tremor, a common manifestation of cerebellar diseases, is aggravated by movement. In contrast, resting tremor is maximal when there is no attempt at voluntary movement, and occurs as a relatively frequent manifestation of Parkinson disease. [NIH] Tricyclic: Containing three fused rings or closed chains in the molecular structure. [EU] Trigger zone: Dolorogenic zone (= producing or causing pain). [EU] Triglyceride: A lipid carried through the blood stream to tissues. Most of the body's fat tissue is in the form of triglycerides, stored for use as energy. Triglycerides are obtained primarily from fat in foods. [NIH] 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] Trypanosome: The trypanosomes are small single-celled parasites (protozoa of the genus Trypanosoma) that are found in the blood-stream in certain diseases that are classed together as the "trypanosomiases". [NIH] Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Tuberculosis: Any of the infectious diseases of man and other animals caused by species of Mycobacterium. [NIH] Tuberous Sclerosis: A rare congenital disease in which the essential pathology is the appearance of multiple tumors in the cerebrum and in other organs, such as the heart or kidneys. [NIH] Tumor Lysis Syndrome: A syndrome resulting from cytotoxic therapy, occurring generally in aggressive, rapidly proliferating lymphoproliferative disorders. It is characterized by combinations of hyperuricemia, lactic acidosis, hyperkalemia, hyperphosphatemia and hypocalcemia. [NIH] Tumor model: A type of animal model which can be used to study the development and
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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] Tumor suppressor gene: Genes in the body that can suppress or block the development of cancer. [NIH] Tympanic membrane: A thin, tense membrane forming the greater part of the outer wall of the tympanic cavity and separating it from the external auditory meatus; it constitutes the boundary between the external and middle ear. [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] Tyramine: An indirect sympathomimetic. Tyramine does not directly activate adrenergic receptors, but it can serve as a substrate for adrenergic uptake systems and monoamine oxidase so it prolongs the actions of adrenergic transmitters. It also provokes transmitter release from adrenergic terminals. Tyramine may be a neurotransmitter in some invertebrate nervous systems. [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] Tyrothricin: A polypeptide antibiotic mixture obtained from Bacillus brevis. It consists of a mixture of three tyrocidines (60%) and several gramicidins (20%) and is very toxic to blood, liver, kidneys, meninges, and the olfactory apparatus. It is used topically. [NIH] Ulcerative colitis: Chronic inflammation of the colon that produces ulcers in its lining. This condition is marked by abdominal pain, cramps, and loose discharges of pus, blood, and mucus from the bowel. [NIH] 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] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Urea: A compound (CO(NH2)2), formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids. [NIH] Uremia: The illness associated with the buildup of urea in the blood because the kidneys are not working effectively. Symptoms include nausea, vomiting, loss of appetite, weakness, and mental confusion. [NIH] Ureters: Tubes that carry urine from the kidneys to the bladder. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]
Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urinary tract: The organs of the body that produce and discharge urine. These include the kidneys, ureters, bladder, and urethra. [NIH] Urinary tract infection: An illness caused by harmful bacteria growing in the urinary tract. [NIH]
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]
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Urine Testing: Checking urine to see if it contains glucose (sugar) and ketones. Special strips of paper or tablets (called reagents) are put into a small amount of urine or urine plus water. Changes in the color of the strip show the amount of glucose or ketones in the urine. Urine testing is the only way to check for the presence of ketones, a sign of serious illness. However, urine testing is less desirable then blood testing for monitoring the level of glucose in the body. [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] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vagal: Pertaining to the vagus nerve. [EU] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Vaginitis: Inflammation of the vagina characterized by pain and a purulent discharge. [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] Valproic Acid: A fatty acid with anticonvulsant properties used in the treatment of epilepsy. The mechanisms of its therapeutic actions are not well understood. It may act by increasing GABA levels in the brain or by altering the properties of voltage dependent sodium channels. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vascular endothelial growth factor: VEGF. A substance made by cells that stimulates new blood vessel formation. [NIH] Vascular Resistance: An expression of the resistance offered by the systemic arterioles, and to a lesser extent by the capillaries, to the flow of blood. [NIH] Vasculitis: Inflammation of a blood vessel. [NIH] Vasoconstriction: Narrowing of the blood vessels without anatomic change, for which constriction, pathologic is used. [NIH] Vasodilator: An agent that widens blood vessels. [NIH] Vasogenic: Acute peripheral circulatory failure due to loss of capillary tone associated with a reduced circulating blood volume. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vegetarianism: Dietary practice of consuming only vegetables, grains, and nuts. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venous: Of or pertaining to the veins. [EU] Venous blood: Blood that has given up its oxygen to the tissues and carries carbon dioxide back for gas exchange. [NIH] 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
372 Hypoglycemia
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] Ventromedial Hypothalamic Nucleus: A nucleus of the middle hypothalamus, the largest cell group of the tuberal region with small-to-medium size cells. [NIH] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Vertebrae: A bony unit of the segmented spinal column. [NIH] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] Vestibule: A small, oval, bony chamber of the labyrinth. The vestibule contains the utricle and saccule, organs which are part of the balancing apparatus of the ear. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Villi: The tiny, fingerlike projections on the surface of the small intestine. Villi help absorb nutrients. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Virilism: Development of masculine traits in the female. [NIH] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the 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] Visceral Afferents: The sensory fibers innervating the viscera. [NIH] Vitamin A: A substance used in cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Vitreous Body: The transparent, semigelatinous substance that fills the cavity behind the crystalline lens of the eye and in front of the retina. It is contained in a thin hyoid membrane and forms about four fifths of the optic globe. [NIH] Vitreous Hemorrhage: Hemorrhage into the vitreous body. [NIH] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] Voltage-gated: It is opened by the altered charge distribution across the cell membrane. [NIH]
Vomica: The profuse and sudden expectoration of pus and putrescent matter. An abnormal cavity in an organ especially in the lung, caused by suppuration and the breaking down of tissue. [NIH] War: Hostile conflict between organized groups of people. [NIH] Weight Gain: Increase in body weight over existing weight. [NIH] Weight-Bearing: The physical state of supporting an applied load. This often refers to the
Dictionary 373
weight-bearing bones or joints that support the body's weight, especially those in the spine, hip, knee, and foot. [NIH] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]
Windpipe: A rigid tube, 10 cm long, extending from the cricoid cartilage to the upper border of the fifth thoracic vertebra. [NIH] Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) A substance-specific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU] Womb: A hollow, thick-walled, muscular organ in which the impregnated ovum is developed into a child. [NIH] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] 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] X-ray therapy: The use of high-energy radiation from x-rays to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. X-ray therapy is also called radiation therapy, radiotherapy, and irradiation. [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] Zygote: The fertilized ovum. [NIH] Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]
375
INDEX 1 1-Propanol, 176, 281 A Abdominal, 95, 281, 282, 294, 329, 330, 334, 345, 347, 370 Abdominal Pain, 281, 330, 334, 370 Ablation, 47, 281 Acceptor, 281, 344 Acetohexamide, 81, 150, 281 Acetylcholine, 281, 298, 342 Acidosis, 125, 191, 200, 207, 213, 218, 281, 306, 324, 369 Acquired Immunodeficiency Syndrome, 87, 281 Acuity, 53, 159, 281 Acute lymphoblastic leukemia, 84, 90, 107, 127, 281 Acute lymphocytic leukemia, 281 Acute renal, 105, 281, 321 Adamantane, 164, 281 Adaptability, 281, 297 Adaptation, 19, 26, 71, 203, 219, 281, 338, 349 Adenine, 59, 282 Adenocarcinoma, 111, 282 Adenosine, 58, 67, 282, 294, 348, 367 Adenosine Kinase, 58, 282 Adenovirus, 282, 358 Adipocytes, 282, 302, 332 Adipose Tissue, 80, 282 Adjustment, 36, 196, 203, 207, 209, 213, 281, 282 Adjuvant, 24, 39, 282, 316 Adjuvant Therapy, 24, 282 Adolescence, 186, 208, 282, 298 Adolescent Nutrition, 186, 208, 214, 282 Adrenal Cortex, 282, 303, 324, 352 Adrenal Glands, 282 Adrenal insufficiency, 175, 188, 282 Adrenal Medulla, 40, 282, 296, 311, 342 Adrenaline, 123, 282 Adrenergic, 15, 27, 76, 108, 159, 174, 224, 240, 282, 288, 308, 311, 365, 370 Adrenergic beta-Antagonists, 282, 288 Adsorption, 61, 283 Adsorptive, 283 Adverse Effect, 64, 67, 74, 283, 361 Aerobic, 50, 283, 313, 337, 344
Aerobic Metabolism, 50, 283, 344 Aerobic Respiration, 283, 344 Aerosols, 283, 357 Afferent, 17, 283, 332 Affinity, 144, 156, 160, 283, 290, 336, 340, 361 Agar, 283, 300, 349 Age Groups, 36, 200, 283 Age of Onset, 283, 293, 370 Aged, 80 and Over, 283 Aggressiveness, 69, 283 Agonist, 144, 145, 155, 176, 177, 181, 283, 308, 325, 330, 338, 341 Agoraphobia, 283, 348 Airways, 283, 357 Akathisia, 284, 288 Alanine, 35, 284, 285 Albumin, 61, 284, 344, 349 Alertness, 284, 294 Algorithms, 56, 152, 284, 292 Alimentary, 9, 116, 224, 284, 307, 311, 346 Alkaline, 281, 284, 285, 294, 367 Alkaloid, 284, 295, 300, 338, 341, 349, 364, 367 Alleles, 25, 284 Allergens, 284, 315 Allograft, 78, 284 Alpha Cell, 59, 284, 317 Alpha-fetoprotein, 284, 314 Alternative medicine, 241, 284 Ameliorating, 154, 155, 173, 180, 181, 284 Amenorrhea, 284, 287 Amine, 284, 322 Amino Acid Sequence, 285, 287, 317 Amino Acid Substitution, 285, 321 Amino Acids, 35, 63, 184, 285, 289, 292, 312, 317, 336, 346, 350, 353, 358, 365, 369, 370 Aminoethyl, 164, 285 Aminopropionitrile, 285, 332 Ammonia, 55, 284, 285, 318, 323, 365, 370 Amniocentesis, 203, 285 Amniotic Fluid, 285, 317 Amphetamine, 285, 286, 292 Amputation, 197, 285 Amygdala, 24, 285, 291, 332, 367 Amylase, 173, 285 Amyloid, 195, 285
376 Hypoglycemia
Anaerobic, 20, 285 Anaesthesia, 102, 285, 326 Anal, 286, 333 Analeptic, 286, 364 Analgesic, 286, 338, 343 Analog, 26, 85, 93, 169, 241, 286, 343 Analogous, 154, 286, 369 Analytes, 32, 151, 152, 262, 286 Anatomical, 286, 325, 340, 359 Androgens, 282, 286, 303, 324 Anemia, 85, 183, 258, 286, 317, 334, 355 Anesthesia, 93, 144, 146, 154, 180, 182, 183, 208, 286, 330, 352 Anesthetics, 286, 311 Angina, 208, 282, 286 Anginal, 286, 342 Angiogenesis, 15, 56, 286 Angiotensin converting enzyme inhibitor, 191, 286 Angiotensin-Converting Enzyme Inhibitors, 286, 288 Animal model, 16, 51, 52, 56, 286, 369 Anionic, 176, 286 Anions, 284, 286, 329 Annealing, 286, 350 Anomalies, 53, 154, 287 Anorexia, 99, 162, 165, 218, 287 Anorexia Nervosa, 99, 162, 165, 218, 287 Anoxia, 66, 142, 143, 147, 155, 163, 181, 182, 184, 287 Antagonism, 22, 142, 180, 287, 294, 367 Antecedent, 16, 24, 43, 44, 81, 82, 102, 106, 287 Anterior Cerebral Artery, 287, 298 Anterograde, 68, 287 Antiallergic, 287, 303 Antibacterial, 287, 363 Antibiotic, 287, 299, 312, 319, 346, 363, 370 Antibodies, 51, 61, 71, 75, 94, 233, 287, 290, 320, 323, 334, 349 Antibody, 61, 68, 149, 153, 178, 179, 283, 287, 301, 320, 322, 325, 326, 330, 335, 338, 355, 356, 363, 373 Anticoagulant, 287, 353 Anticonvulsant, 18, 287, 295, 371 Antidiabetic, 161, 166, 167, 168, 200, 246, 287, 318 Antidiabetic Agent, 166, 167, 200, 246, 287 Antidote, 99, 287 Antiemetic, 287, 288 Antigen, 51, 283, 284, 287, 288, 301, 322, 324, 325, 326, 328, 335, 358
Antigen-presenting cell, 51, 288 Antihypertensive, 163, 208, 288 Antihypertensive Agents, 163, 288 Anti-infective, 288, 315, 361 Anti-Infective Agents, 288, 315 Anti-inflammatory, 122, 288, 289, 303, 317, 326, 359, 362 Anti-Inflammatory Agents, 288, 289, 303 Antineoplastic, 288, 303, 327 Antineoplastic Agents, 288, 327 Antioxidant, 175, 288 Antipsychotic, 163, 288, 340 Antipyretic, 288 Anuria, 288, 331 Anxiolytic, 176, 288 Aorta, 150, 288, 308, 346, 351, 363, 372 Apolipoproteins, 288, 333 Apoptosis, 21, 56, 58, 59, 170, 183, 288, 296 Appendicitis, 210, 289 Approximate, 30, 289, 315 Aqueous, 289, 291, 304 Arcuate Nucleus, 45, 289 Arginine, 59, 79, 114, 289, 342 Aromatic, 289, 292, 336, 348 Arrhythmia, 53, 147, 289 Arterial, 150, 289, 293, 298, 324, 329, 346, 353, 366, 369 Arteries, 150, 288, 289, 293, 297, 298, 303, 330, 333, 336, 338, 363 Arterioles, 289, 293, 295, 371 Arteriolosclerosis, 289 Arteriosclerosis, 153, 289, 324, 363 Arteriovenous, 289, 298 Articular, 289, 344 Aspartate, 48, 142, 143, 144, 147, 155, 160, 163, 179, 180, 181, 182, 184, 289, 330, 348 Aspartic, 176, 289, 312 Aspartic Acid, 176, 289 Asphyxia, 142, 143, 147, 163, 182, 184, 289 Aspiration, 289, 314 Aspirin, 147, 191, 289, 362 Assay, 24, 34, 108, 149, 178, 290 Astrocytes, 33, 45, 46, 290, 317, 340 Asymptomatic, 7, 9, 70, 114, 174, 290 Ataxia, 53, 78, 258, 290, 295, 297, 323, 325, 367 Atrial, 290, 366 Atrophy, 81, 155, 181, 258, 290, 340 Attenuated, 21, 290 Auditory, 5, 290, 335, 370, 371 Autacoids, 290, 326 Autoantibodies, 75, 105, 290
Index 377
Autoantigens, 290 Autoimmune disease, 59, 290 Autoimmunity, 51, 290 Automobile Driving, 266, 290 Autonomic Nervous System, 16, 17, 35, 43, 44, 204, 290, 347, 362, 365 Autonomic Neuropathy, 16, 190, 290 Autosuggestion, 291, 325 Axonal, 52, 291 B Back Pain, 193, 210, 291 Bacteria, 54, 283, 287, 291, 299, 310, 314, 319, 337, 360, 363, 369, 370, 371 Bacterial Physiology, 282, 291 Bactericidal, 291, 312 Bacteriophage, 291, 349, 369 Baroreflex, 17, 291 Basal Ganglia, 288, 290, 291, 293, 298, 332 Basal Ganglia Diseases, 290, 291, 298 Base, 147, 282, 291, 295, 305, 312, 317, 320, 330, 331, 366 Basement Membrane, 291, 313, 331 Basophils, 291, 319, 332 Behavior Therapy, 291 Benign, 55, 195, 289, 291, 293, 296, 320, 339, 345, 355 Beta-pleated, 285, 291 Bewilderment, 292, 302 Bilateral, 292, 357 Bile, 292, 316, 333, 364 Bilirubin, 284, 292 Binding Sites, 49, 156, 292 Bioavailability, 168, 292 Biochemical, 17, 31, 55, 64, 94, 200, 284, 292, 295, 314, 331, 360 Biogenesis, 54, 292 Biogenic Amines, 48, 292 Biological response modifier, 292, 328 Biological therapy, 292, 320 Biological Transport, 292, 307 Biosynthesis, 153, 292 Biotechnology, 71, 72, 223, 241, 253, 257, 258, 259, 292 Bivalent, 292, 336 Bladder, 208, 291, 292, 304, 326, 340, 353, 370 Blastocyst, 292, 302, 310, 349 Bloating, 292, 316, 326, 330, 334 Blood Coagulation, 292, 293, 294, 295, 314, 367 Blood Coagulation Factors, 292, 295
Blood Glucose, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 24, 27, 29, 30, 34, 35, 36, 37, 39, 42, 50, 51, 54, 55, 60, 61, 70, 73, 83, 95, 110, 115, 125, 145, 148, 150, 151, 152, 156, 158, 159, 160, 166, 167, 168, 169, 170, 171, 172, 174, 175, 177, 179, 187, 188, 189, 190, 191, 192, 193, 194, 196, 197, 198, 199, 200, 201, 202, 203, 205, 206, 207, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 225, 226, 228, 229, 230, 232, 233, 235, 236, 237, 242, 254, 255, 264, 265, 266, 293, 318, 321, 324, 328 Blood Platelets, 293, 360 Blood Volume, 293, 371 Body Fluids, 293, 308, 314, 342, 361 Bolus, 94, 198, 214, 293 Bolus infusion, 293 Bone Marrow, 281, 293, 300, 325, 334, 362 Bowel, 145, 286, 293, 307, 311, 327, 328, 332, 340, 343, 364, 370 Bowel Movement, 293, 307, 364 Brachytherapy, 293, 328, 329, 355, 373 Bradykinin, 293, 342, 349 Brain Hypoxia, 293, 367 Brain Infarction, 293 Brain Ischemia, 33, 49, 293, 298 Brain Neoplasms, 293, 323, 367 Brain Stem, 293, 294, 297, 298 Branch, 114, 237, 275, 294, 304, 309, 310, 317, 334, 335, 341, 346, 354, 362, 365, 367 Breakdown, 45, 63, 294, 297, 306, 307, 316 Bronchi, 294, 311, 367, 368 Bronchial, 123, 294, 322, 353, 367 Bronchitis, 192, 210, 294 Bronchopulmonary, 294, 357 Buffers, 291, 294 Bupivacaine, 294, 332 Burns, 210, 294 Burns, Electric, 294 C Caesarean section, 38, 294 Caffeine, 7, 108, 147, 203, 213, 241, 267, 286, 294 Calcification, 289, 294 Calcium, 15, 46, 122, 156, 180, 186, 191, 208, 288, 294, 295, 301, 324, 342, 344, 346, 361, 367 Calcium channel blocker, 191, 288, 294 Calcium Channel Blockers, 191, 288, 294 Calcium Channels, 156, 295 Calcium Oxalate, 295, 344 Callus, 295, 310
378 Hypoglycemia
Calmodulin, 122, 295 Canonical, 25, 295 Capillary, 7, 10, 15, 61, 108, 293, 295, 371, 372 Capsaicin, 191, 295 Capsules, 7, 114, 295, 316 Carbamazepine, 18, 295 Carbohydrate-Deficient Glycoprotein Syndrome, 127, 295 Carbon Dioxide, 295, 304, 322, 349, 357, 371 Carcinogenic, 295, 327, 343, 352, 364 Carcinogens, 295, 299, 343 Carcinoid, 77, 104, 116, 295, 340 Carcinoma, 89, 295, 296, 340 Cardiac arrest, 142, 143, 147, 155, 163, 164, 180, 181, 182, 184, 296, 365 Cardiac Output, 291, 296 Cardiopulmonary, 296, 357 Cardiotonic, 296, 307 Cardiovascular disease, 17, 42, 172, 173, 174, 175, 216, 217, 296 Cardiovascular System, 17, 176, 291, 296 Carotene, 296, 357 Case report, 77, 97, 103, 105, 111, 127, 194, 296, 299 Case series, 296, 299 Caspase, 45, 296 Catecholamine, 15, 22, 86, 296, 308, 347 Catheters, 35, 209, 296, 326, 328 Cations, 296, 329 Caudal, 296, 306, 324, 350 Causal, 42, 147, 151, 182, 296, 366 Cause of Death, 24, 46, 47, 150, 151, 157, 173, 296 Cell Adhesion, 183, 297, 328 Cell Cycle, 58, 68, 297, 304 Cell Death, 33, 45, 48, 52, 58, 122, 180, 288, 297, 339 Cell Differentiation, 297, 361 Cell Division, 258, 291, 297, 304, 320, 335, 337, 349, 352 Cell membrane, 52, 82, 155, 181, 292, 294, 295, 297, 306, 316, 329, 348, 351, 361, 372 Cell proliferation, 15, 289, 297, 358, 361 Cell Respiration, 283, 297, 337, 344, 357 Cell Survival, 297, 320 Cell Transplantation, 39, 197, 200, 262, 297 Cellular metabolism, 58, 297 Cellulose, 297, 349 Central Nervous System, 21, 35, 48, 55, 142, 143, 146, 148, 162, 163, 165, 177,
179, 180, 182, 183, 281, 284, 285, 290, 291, 293, 294, 295, 297, 298, 300, 316, 318, 320, 323, 338, 339, 341, 344, 360, 367 Central Nervous System Infections, 297, 320, 323 Cerebellar, 49, 78, 290, 295, 297, 356, 369 Cerebellar Diseases, 290, 297, 369 Cerebellum, 293, 297, 298, 356 Cerebral Arteries, 150, 297, 337 Cerebral Infarction, 142, 143, 147, 163, 182, 184, 293, 297, 298, 323 Cerebrospinal, 99, 126, 298, 323 Cerebrospinal fluid, 99, 126, 298, 323 Cerebrovascular, 46, 142, 143, 147, 151, 163, 182, 184, 191, 201, 291, 294, 296, 298, 367 Cerebrovascular Disorders, 142, 143, 147, 163, 182, 184, 298, 367 Cerebrum, 297, 298, 369 Character, 186, 189, 230, 298, 305 Chemoreceptor, 288, 298 Chemotherapy, 56, 105, 282, 298 Chest Pain, 193, 210, 298 Child Development, 200, 298 Chlorides, 162, 298 Cholesterol, 150, 175, 187, 204, 205, 212, 214, 292, 298, 299, 303, 309, 324, 333, 364 Cholesterol Esters, 298, 333 Cholinergic, 48, 174, 288, 298, 341 Chorea, 288, 298 Chorioretinitis, 298, 357 Choroid, 298, 357 Chromatin, 289, 299, 311, 341 Chromium, 24, 116, 118, 175, 299 Chromosomal, 299, 358, 359 Chromosome, 299, 320, 330, 332, 359 Chronic Disease, 32, 69, 157, 192, 299 Chronic renal, 90, 111, 299, 350 Chylomicrons, 299, 333 Circadian, 65, 299 Circulatory system, 179, 299, 310 CIS, 299, 357 Clamp, 15, 22, 299 Clarithromycin, 105, 299 Clinical Medicine, 299, 351 Clinical study, 224, 299, 302 Clinical trial, 8, 14, 28, 29, 31, 48, 71, 137, 138, 253, 299, 302, 346, 354, 356 Clone, 54, 299 Cloning, 46, 292, 299 Coagulation, 292, 300, 321, 349, 367 Coca, 300
Index 379
Cocaine, 90, 300 Cochlea, 300, 327 Coenzymes, 300, 341 Cofactor, 300, 353, 367 Cognition, 28, 146, 155, 164, 180, 182, 300, 340 Cognitive behavior therapy, 63, 300 Colitis, 300, 330 Collagen, 150, 291, 300, 313, 314, 316, 349, 352 Collapse, 49, 294, 300, 361 Colloidal, 284, 300, 309 Colonic Neoplasms, 56, 300 Colony-Stimulating Factors, 300, 319 Colorectal, 111, 300 Colostrum, 176, 301 Comatose, 9, 301 Combination Therapy, 166, 198, 208, 301 Common Bile Duct, 301, 345 Comorbidity, 200, 301 Complement, 301, 317, 328, 330, 349 Complementary and alternative medicine, 121, 134, 301 Complementary medicine, 121, 301 Compress, 301, 321 Computational Biology, 253, 257, 301 Conception, 225, 302, 314, 335, 351, 363 Concomitant, 6, 26, 34, 302 Cone, 302, 365 Confusion, 9, 159, 167, 175, 193, 266, 278, 302, 307, 324, 340, 370 Congestion, 288, 302 Congestive heart failure, 208, 302 Conjunctiva, 302, 327 Connective Tissue, 200, 293, 300, 302, 314, 316, 333, 336, 358 Connective Tissue Cells, 302 Connexins, 302, 316 Consciousness, 4, 159, 175, 193, 266, 267, 278, 286, 302, 305, 307, 311, 321, 357, 363, 366 Constipation, 210, 288, 302, 330 Constitutional, 302, 338, 357 Constriction, 302, 330, 359, 371 Consumption, 8, 206, 209, 227, 241, 302, 306, 342, 345 Contamination, 24, 302, 321 Contraceptive, 203, 302, 358 Contraindications, ii, 302 Control group, 29, 302 Controlled clinical trial, 60, 302 Conventional therapy, 302, 303
Conventional treatment, 186, 302, 303 Convulsion, 164, 303 Convulsive, 147, 182, 303 Coordination, 8, 28, 297, 303 Coronary, 150, 296, 303, 336, 338 Coronary heart disease, 296, 303 Coronary Thrombosis, 303, 336, 338 Cortex, 15, 45, 52, 290, 297, 303, 311, 312, 337, 356 Cortical, 20, 49, 111, 122, 123, 127, 164, 303, 312, 360, 367 Corticosteroid, 89, 303 Cortisol, 20, 43, 44, 65, 79, 83, 86, 98, 106, 227, 284, 303 Cranial, 110, 297, 303, 320, 329, 340, 343, 347, 371 Craniocerebral Trauma, 291, 303, 320, 323, 367 Creatinine, 198, 303, 331 Critical Care, 47, 73, 303 Cross-Sectional Studies, 71, 303 Cryostat, 304, 315 Cues, 231, 304 Curative, 304, 341, 367 Cutaneous, 190, 200, 208, 304 Cyanide, 155, 181, 304 Cyanosis, 304, 321 Cyclic, 47, 184, 294, 295, 304, 319, 320, 342, 353, 359, 367 Cyclin, 68, 304 Cysteine, 175, 304, 365 Cystine, 304 Cystitis, 155, 181, 304 Cytogenetics, 304, 359 Cytokine, 43, 71, 170, 304 Cytoplasm, 289, 291, 297, 304, 310, 311, 319, 336, 341, 358, 366 Cytoskeleton, 304, 328 Cytotoxic, 51, 175, 295, 304, 356, 361, 369 D Data Collection, 36, 38, 41, 304 Databases, Bibliographic, 253, 304 Day Care, 200, 212, 304 Deamination, 304, 370 Decarboxylation, 292, 304, 322, 338 Decidua, 304, 337, 349 Decision Making, 210, 305 Decompensation, 38, 41, 305 Decubitus, 305, 361 Decubitus Ulcer, 305, 361 Defense Mechanisms, 305, 328
380 Hypoglycemia
Degenerative, 142, 143, 147, 155, 163, 176, 181, 305, 317, 321, 334, 338, 358 Dehydration, 31, 305, 324 Deletion, 40, 51, 55, 110, 289, 305, 316 Delirium, 288, 305 Delusions, 305, 354 Dementia, 142, 155, 164, 176, 181, 281, 288, 305 Denaturation, 305, 350 Dendrites, 305, 306, 341 Dendritic, 52, 305, 335 Density, 175, 305, 308, 333, 343, 350 Dental Care, 198, 199, 305 Dentate Gyrus, 305, 322 Depolarization, 49, 65, 156, 306, 361 Depressive Disorder, 28, 306, 333 Deprivation, 33, 59, 306 Detergents, 306, 361 Detoxification, 55, 130, 306 Developed Countries, 306, 315 Diabetes, Gestational, 207, 306, 351 Diabetic Foot, 190, 195, 201, 207, 213, 218, 306 Diabetic Retinopathy, 16, 146, 147, 183, 187, 190, 191, 197, 216, 217, 306 Diagnostic procedure, 141, 221, 242, 306 Dialyzer, 306, 321 Diaphoresis, 174, 306 Diarrhea, 129, 208, 210, 306, 330, 334 Diastolic, 306, 324 Diencephalon, 298, 306, 324, 367 Dietary Fiber, 122, 186, 189, 208, 307 Dietetics, 225, 226, 307 Dietitian, 199, 307 Diffusion, 77, 292, 307, 327, 329 Digestion, 173, 284, 292, 293, 307, 309, 316, 326, 328, 333, 345, 364 Digestive system, 139, 209, 307 Digestive tract, 173, 291, 307, 361 Digitalis, 147, 307 Dilatation, 307, 351 Dilation, 293, 307, 323 Diploid, 307, 349 Direct, iii, 21, 25, 33, 50, 63, 151, 157, 215, 245, 299, 307, 308, 356, 365 Discrimination, 4, 12, 193, 202, 307 Disinfectant, 307, 312 Dislocation, 307, 363 Disorientation, 302, 305, 307 Dissociation, 283, 307 Distal, 291, 307, 331, 347, 351, 354 Diuresis, 148, 294, 307, 367
Diuretic, 307, 362 Diuretics, Thiazide, 288, 307 Diurnal, 65, 308 Dizziness, 9, 159, 193, 210, 263, 267, 278, 308 Dopamine, 48, 285, 288, 300, 308, 348 Dorsal, 308, 350, 363 Dosage schedule, 229, 308 Drug Interactions, 191, 229, 246, 308 Drug Monitoring, 82, 308 Drug Resistance, 58, 308 Drug Tolerance, 308, 368 Duct, 301, 308, 313, 346, 359 Ductus Arteriosus, 308 Dumping Syndrome, 101, 308 Duodenum, 292, 308, 316, 345, 364 Dyes, 285, 291, 308, 315, 341, 347 Dyskinesia, 164, 288, 308 Dyslipidemia, 200, 208, 213, 219, 308 Dyspepsia, 309, 326 Dysphoric, 306, 309 Dysplasia, 258, 309 Dyspnea, 305, 309 Dystonia, 288, 309 Dystrophy, 145, 258, 309 E Eating Disorders, 99, 129, 193, 209, 309 Edema, 46, 164, 305, 306, 309, 321, 329 Effector, 17, 20, 54, 281, 301, 309, 340, 341 Effector cell, 309, 340, 341 Efficacy, 18, 60, 61, 82, 85, 166, 309 Elasticity, 289, 309 Elastin, 150, 300, 309, 313 Elective, 309 Electrolyte, 303, 305, 309, 314, 331, 337, 342, 351, 361 Electrons, 288, 291, 309, 329, 334, 344, 355 Electrophoresis, 46, 309 Electrophysiological, 33, 66, 162, 165, 309 Elementary Particles, 309, 334, 341, 354 Emaciation, 281, 309 Emboli, 309, 329, 363 Embryo, 292, 297, 310, 326, 351, 363 Embryo Transfer, 310, 351 Embryogenesis, 52, 310 Emergency Medicine, 34, 90, 99, 195, 310 Emergency Treatment, 85, 232, 310 Emesis, 164, 310 Emollient, 310, 318, 343 Emphysema, 192, 310 Empirical, 60, 310 Encephalopathy, 75, 310
Index 381
Endemic, 310, 334, 363 Endocrine System, 310, 340 Endometrium, 304, 310, 336, 337 Endothelial cell, 15, 19, 46, 310, 367 Endothelium, 310, 342 Endothelium-derived, 310, 342 Endotoxic, 310, 333 Endotoxins, 301, 310, 330 End-stage renal, 241, 299, 311, 350 Energy balance, 311, 332 Enhancer, 68, 311, 357 Enteral Nutrition, 186, 311 Enteritis, 80, 186, 208, 311 Enterocolitis, 311 Entorhinal Cortex, 311, 322 Environmental Exposure, 311, 343 Environmental Health, 252, 254, 311 Enzymatic, 18, 227, 292, 294, 296, 301, 311, 322, 350, 357 Eosinophils, 311, 319, 332 Ependyma, 289, 311, 367 Epidemic, 40, 222, 311, 363 Epigastric, 311, 345 Epilepticus, 58, 311 Epinephrine, 9, 13, 22, 27, 44, 47, 48, 59, 65, 138, 159, 227, 282, 292, 308, 311, 342, 370 Epithelial, 47, 282, 292, 304, 311, 331, 345 Epithelial Cells, 47, 311, 331 Equipment and Supplies, 214, 216, 237, 311 Erectile, 194, 197, 208, 219, 311, 312 Erection, 225, 311, 312, 349 Erythrocytes, 286, 293, 312 Erythromycin, 299, 312 Esophagus, 307, 312, 320, 348, 356, 364 Essential Tremor, 258, 312 Estrogen, 44, 83, 312 Ethanol, 55, 312 Ether, 93, 114, 116, 312 Eukaryotic Cells, 312, 326 Evacuation, 302, 312, 316, 332 Evoke, 312, 364 Excipients, 154, 312, 315, 347 Excitability, 52, 66, 312, 340 Excitation, 48, 65, 142, 143, 147, 160, 163, 180, 182, 184, 298, 312 Excitatory Amino Acid Agonists, 312, 330 Excitatory Amino Acid Antagonists, 159, 160, 312
Excitatory Amino Acids, 142, 143, 144, 146, 147, 154, 155, 163, 180, 181, 182, 183, 312, 341 Excitotoxicity, 45, 49, 147, 155, 181, 182, 312 Excrete, 288, 313, 331 Exercise Test, 43, 313 Exhaustion, 287, 313, 334 Exocrine, 313, 345 Exogenous, 17, 35, 39, 283, 313, 370 Expert Systems, 313, 315 Expiration, 313, 357 External-beam radiation, 313, 329, 355, 373 Extracellular, 35, 37, 49, 65, 107, 150, 183, 285, 290, 302, 313, 314, 328, 337, 340, 353, 361, 367 Extracellular Matrix, 183, 302, 313, 314, 328 Extracellular Matrix Proteins, 183, 313 Extracellular Space, 313, 337 Extrapyramidal, 284, 288, 308, 313 Extremity, 208, 313 F Failure to Thrive, 186, 208, 313 Family Planning, 253, 313 Fatigue, 9, 128, 135, 175, 278, 290, 313, 320 Fatty acids, 186, 208, 284, 306, 313, 352, 361 Fatty Liver, 295, 314 Feces, 302, 314, 364 Fertilization in Vitro, 314, 351 Fetal Blood, 308, 314, 349 Fetal Death, 12, 314 Fetal Monitoring, 203, 314 Fetoprotein, 203, 314 Fetus, 32, 38, 41, 284, 314, 349, 363, 364, 371 Fibrin, 292, 314, 367 Fibrinogen, 61, 314, 349, 367 Fibroblasts, 302, 314, 328 Fibronectins, 313, 314 Fibrosis, 258, 314, 321, 359 Fistula, 314, 343 Flatus, 314, 316 Flavoring Agents, 314, 315, 347 Fluid Therapy, 208, 314, 342 Fluorescence, 126, 314 Fold, 16, 44, 58, 62, 148, 151, 314, 345 Food Additives, 208, 314 Food Coloring Agents, 315 Food Exchange, 215, 315
382 Hypoglycemia
Food Habits, 237, 315 Food Hypersensitivity, 186, 208, 315 Food Labeling, 186, 315 Food Preferences, 315 Food Preservatives, 315 Foot Care, 189, 191, 198, 206, 207, 215, 216, 218, 315 Foot Ulcer, 194, 208, 306, 315 Forearm, 10, 293, 315 Fractionation, 19, 315 Frontal Lobe, 287, 298, 315 Frozen Sections, 84, 315 Fructosamine, 215, 315 Fructose, 34, 85, 149, 159, 178, 315, 319 Functional magnetic resonance imaging, 109, 315 Fuzzy Logic, 158, 315 G Galactosemia, 97, 316 Gallbladder, 281, 307, 316, 345 Ganglia, 17, 281, 291, 316, 340, 347, 365 Ganglionic Blockers, 288, 316 Gangrene, 167, 316 Gap Junctions, 33, 302, 316, 365, 366 Gas, 61, 285, 295, 307, 314, 316, 323, 326, 330, 334, 342, 371 Gastric, 122, 147, 224, 316, 320, 322, 323 Gastric Emptying, 224, 316 Gastrin, 316, 322 Gastrointestinal tract, 218, 312, 316, 360, 362 Gastroparesis, 8, 197, 236, 316 Gastrostomy, 311, 316 Gavage, 314, 316 Gelatin, 316, 318, 365 Gels, 264, 316 Gene Deletion, 55, 316 Gene Expression, 18, 22, 25, 29, 34, 39, 54, 57, 183, 259, 316, 362 General practitioner, 206, 317 Genetic Code, 317, 342 Genetic Counseling, 207, 215, 317 Genetic Engineering, 292, 299, 317 Genetic testing, 203, 317, 350 Genetics, 84, 87, 190, 195, 304, 317 Genital, 291, 317 Genomics, 47, 317 Genotype, 13, 317, 348 Geriatric, 208, 317 Gestation, 33, 38, 41, 64, 203, 317, 347, 349, 363
Gestational, 12, 38, 41, 62, 88, 103, 193, 197, 198, 202, 213, 215, 216, 228, 255, 317 Gestational Age, 88, 317 Ginseng, 124, 130, 131, 133, 317 Gland, 162, 165, 218, 282, 317, 324, 333, 345, 349, 353, 359, 364, 368 Gliosis, 45, 317 Glipizide, 157, 317 Glomerular, 317, 331, 356 Glossitis, 317 Glucagonoma, 103, 317 Glucocorticoid, 40, 43, 65, 317, 337 Glucokinase, 79, 94, 149, 178, 318 Gluconeogenesis, 34, 35, 175, 318 Glucose Clamp Technique, 44, 318 Glucose Intolerance, 38, 41, 191, 231, 306, 318 Glucose Tolerance Test, 47, 213, 264, 318 Glutamate Dehydrogenase, 54, 318 Glutamic Acid, 180, 318, 352 Glutamine, 35, 149, 178, 318 Glyburide, 12, 110, 132, 157, 166, 318 Glycerol, 35, 44, 55, 102, 318, 348 Glycine, 144, 180, 184, 318, 364 Glycogen, 40, 45, 77, 80, 81, 88, 114, 124, 146, 148, 178, 179, 318, 319 Glycogen Storage Disease, 80, 318 Glycogen Synthase, 40, 77, 81, 114, 319 Glycolysis, 20, 50, 319 Glycoprotein, 183, 314, 319, 331, 367 Glycosaminoglycans, 313, 319 Glycoside, 168, 319, 359 Gonadal, 319, 364 Gonads, 319, 324 Governing Board, 319, 351 Gp120, 164, 319 Grade, 125, 187, 205, 266, 319 Graft, 319, 323, 325 Graft Rejection, 319, 325 Grafting, 319, 326 Gramicidin, 49, 319 Gram-positive, 319 Granulocyte Colony-Stimulating Factor, 80, 300, 319 Granulocytes, 300, 319, 361, 373 Growth factors, 43, 62, 190, 320 Guanidine, 160, 320 Guanylate Cyclase, 320, 342 H Habitual, 298, 320 Haematemesis, 310, 320 Hallucinogen, 320, 348
Index 383
Haploid, 320, 349 Haptens, 283, 320 Headache Disorders, 320 Health Status, 53, 320 Heart attack, 296, 320 Heart failure, 286, 320 Heartbeat, 4, 8, 266, 267, 278, 320, 365 Heartburn, 210, 214, 320, 326 Hemangiopericytoma, 86, 95, 99, 320 Hematoma, 320, 321 Heme, 15, 292, 320, 321 Hemiparesis, 79, 320 Hemochromatosis, 218, 321 Hemodialysis, 107, 219, 306, 321, 331 Hemoglobin, 6, 7, 11, 13, 61, 166, 171, 194, 196, 197, 203, 215, 217, 233, 286, 304, 312, 320, 321, 332, 345 Hemoglobin A, 215, 321 Hemoglobin M, 203, 304, 321 Hemoglobinuria, 258, 321 Hemolytic, 321, 355 Hemorrhage, 150, 151, 303, 320, 321, 364, 372 Hemorrhagic stroke, 57, 142, 143, 147, 163, 182, 184, 321 Hemostasis, 321, 328, 360 Hepatic, 9, 29, 39, 63, 81, 99, 103, 114, 124, 155, 166, 181, 227, 284, 301, 305, 318, 321 Hepatic Encephalopathy, 155, 181, 321 Hepatitis, 218, 321 Hepatitis A, 321, 322 Hepatitis, Alcoholic, 218, 321 Hepatoblastoma, 92, 322 Hepatocyte, 68, 322 Hepatotoxic, 127, 322 Hereditary, 169, 322, 338, 340, 358 Heredity, 198, 316, 317, 322 Heterodimers, 322, 328 Heterogeneity, 283, 322 Hippocampus, 33, 45, 52, 57, 306, 322, 332, 364 Hirsutism, 322, 324 Histamine, 22, 288, 292, 322 Histamine Agonists, 322 Histamine Antagonists, 22, 322 Histidine, 22, 322 Histidine Decarboxylase, 22, 322 Holidays, 196, 202, 219, 322 Homeopathic remedies, 195, 322 Homeostasis, 20, 28, 37, 39, 43, 49, 65, 66, 87, 146, 178, 195, 227, 231, 322, 362 Homologous, 284, 292, 302, 322, 366
Hormonal, 11, 30, 32, 34, 43, 59, 62, 80, 85, 96, 97, 98, 106, 215, 227, 231, 240, 290, 303, 322 Hormone Replacement Therapy, 198, 323 Hormone therapy, 86, 282, 323 Host, 51, 54, 153, 179, 291, 323, 325, 345, 358, 372 Hybrid, 299, 323 Hybridization, 20, 323 Hybridomas, 323, 328 Hydrocephalus, 126, 323, 329 Hydrochloric Acid, 298, 323 Hydrogen, 281, 284, 291, 294, 295, 305, 313, 323, 338, 341, 342, 344, 354 Hydrolysis, 34, 66, 155, 181, 289, 323, 329, 333, 348, 350, 354 Hydrophilic, 168, 306, 323 Hydrophobic, 306, 323, 333 Hydroxylysine, 300, 323 Hydroxyproline, 300, 323 Hydroxysteroids, 123, 323 Hygienic, 323, 361 Hyperammonemia, 54, 102, 323 Hyperandrogenism, 219, 324 Hypercalcemia, 219, 324 Hypercholesterolemia, 308, 324 Hyperglycemic Hyperosmolar Nonketotic Coma, 215, 324 Hyperlipidemia, 186, 207, 208, 308, 324 Hypersensitivity, 165, 284, 324, 358 Hypertriglyceridemia, 308, 324 Hyperuricemia, 324, 369 Hypoglycaemia, 152, 154, 305, 324 Hypoglycemic Agents, 13, 94, 105, 146, 150, 158, 161, 175, 194, 201, 203, 207, 212, 218, 232, 324 Hypogonadism, 219, 324 Hypolipidemic, 152, 175, 324 Hypotension, 208, 288, 316, 324 Hypothalamic, 17, 22, 26, 38, 45, 65, 87, 324, 362 Hypothalamus, 22, 24, 31, 35, 45, 136, 289, 290, 293, 306, 324, 332, 349, 362, 367, 372 Hypothermia, 324 Hypothyroidism, 295, 324 I Iatrogenic, 43, 325 Ibotenic Acid, 325, 338 Ice Cream, 209, 325 Id, 48, 117, 128, 262, 263, 268, 274, 276, 325 Idiopathic, 9, 174, 325
384 Hypoglycemia
Immune response, 282, 287, 288, 290, 303, 319, 320, 325, 365, 372 Immune system, 51, 162, 165, 214, 288, 290, 292, 309, 322, 325, 334, 339, 347, 371, 373 Immunity, 186, 281, 284, 325 Immunization, 325 Immunodeficiency, 79, 147, 162, 165, 182, 258, 281, 325 Immunogenic, 325, 333 Immunoglobulin, 287, 325, 338 Immunologic, 317, 325, 356 Immunology, 51, 218, 282, 283, 325 Immunosuppressive, 59, 317, 325 Immunosuppressive therapy, 325 Immunotherapy, 51, 292, 325 Impairment, 11, 12, 14, 16, 40, 45, 52, 93, 110, 242, 290, 292, 298, 305, 308, 325, 336, 354 Implant radiation, 326, 328, 329, 355, 373 Implantable pump, 50, 326 Implantation, 39, 302, 326 Impotence, 197, 198, 214, 312, 326 In situ, 19, 20, 22, 46, 326 In Situ Hybridization, 20, 22, 326 In vitro, 25, 33, 46, 49, 50, 51, 61, 94, 164, 310, 326, 350 In vivo, 23, 24, 25, 30, 32, 33, 46, 47, 51, 61, 94, 99, 126, 164, 170, 180, 326, 337 Incision, 294, 326, 329 Incontinence, 142, 143, 146, 147, 154, 155, 163, 164, 176, 180, 181, 182, 323, 326 Incubated, 34, 326 Indicative, 6, 220, 326, 346, 371 Indigestion, 214, 326 Indomethacin, 101, 115, 326 Induction, 14, 15, 48, 58, 68, 80, 153, 179, 286, 288, 316, 326, 330 Infant Nutrition, 186, 208, 326 Infant, Newborn, 283, 326 Infarction, 298, 321, 326, 357, 363 Infertility, 162, 165, 214, 327 Infiltration, 322, 327, 352 Inflammatory bowel disease, 145, 327 Influenza, 164, 213, 327 Infuse, 327 Infusion, 9, 27, 39, 79, 83, 85, 103, 214, 254, 318, 327, 328 Infusion Pumps, 39, 254, 327 Ingestion, 7, 30, 101, 115, 226, 280, 318, 327, 328, 332, 345, 350, 367 Inhalation, 283, 327, 350
Initiation, 18, 37, 45, 327, 352, 368 Inlay, 327, 357 Inner ear, 66, 327 Innervation, 63, 327 Inorganic, 176, 298, 327, 338 Inositol, 327, 336, 359 Inotropic, 308, 327 Insecticides, 327, 347 Insight, 26, 28, 33, 52, 54, 66, 327 Insomnia, 147, 327 Insulin Infusion Systems, 327, 328 Insulin-dependent diabetes mellitus, 31, 39, 45, 146, 149, 158, 169, 178, 215, 254, 328 Insulin-like, 75, 89, 90, 93, 95, 96, 328 Insulin-Like Growth Factor I, 72, 96, 328 Integrins, 183, 328 Interferon, 71, 328, 334 Interferon-alpha, 328 Interindividual, 10, 328 Interleukin-6, 71, 127, 328 Intermittent, 43, 314, 328 Internal radiation, 328, 329, 355, 373 Interstitial, 6, 7, 35, 293, 313, 328, 329, 356, 373 Intestinal, 47, 193, 296, 311, 318, 328, 334 Intestine, 64, 168, 218, 293, 311, 328, 331, 355 Intoxication, 305, 329, 373 Intracellular, 19, 21, 45, 58, 67, 92, 157, 294, 326, 328, 329, 336, 342, 351, 353, 356, 359, 361 Intracranial Embolism, 298, 329 Intracranial Embolism and Thrombosis, 298, 329 Intracranial Hemorrhages, 323, 329, 367 Intracranial Hypertension, 320, 323, 329 Intrahepatic, 59, 87, 329 Intraindividual, 10, 329 Intramuscular, 329, 346 Intraperitoneal, 50, 329 Intravenous, 35, 84, 103, 116, 150, 231, 327, 329, 346 Intrinsic, 35, 64, 283, 291, 329 Invasive, 21, 25, 32, 39, 56, 151, 197, 200, 325, 329, 334, 345 Invertebrates, 318, 329 Involuntary, 291, 298, 303, 312, 329, 338, 339, 349, 362 Ion Channels, 47, 52, 290, 329, 340, 341, 366 Ion Transport, 329, 337
Index 385
Ionizing, 311, 329, 335, 355 Ions, 65, 291, 294, 295, 307, 308, 309, 320, 323, 329, 338, 351, 361 Irradiation, 213, 329, 373 Irritable Bowel Syndrome, 162, 165, 330 Ischemic stroke, 15, 57, 330 Isozymes, 330, 355 J Jejunostomy, 311, 330 Jet lag, 230, 330 Joint, 219, 289, 330, 363, 365 K Kainate, 144, 184, 330 Kainic Acid, 155, 181, 330 Karyotype, 285, 330 Kb, 252, 330 Ketamine, 330, 348 Keto, 143, 330 Ketone Bodies, 306, 330, 331 Ketonuria, 187, 330 Ketosis, 306, 324, 331 Kidney Cortex, 331, 336 Kidney Failure, 167, 216, 219, 237, 311, 331 Kidney Failure, Acute, 331 Kidney Failure, Chronic, 331 Kidney stone, 331, 344 Kidney Transplantation, 219, 331 Kinetic, 20, 329, 331 L Labyrinth, 300, 327, 331, 360, 372 Laceration, 331, 366 Lactation, 301, 331, 345 Lag, 61, 331 Laminin, 291, 313, 331 Large Intestine, 307, 328, 331, 356, 361 Larynx, 331, 368, 371 Latent, 331, 351 Lathyrism, 142, 143, 147, 163, 182, 332 Laxative, 283, 332, 362 Leprosy, 315, 332 Leptin, 21, 35, 332 Lesion, 40, 150, 315, 317, 321, 332, 333, 366 Lethal, 51, 291, 304, 332 Lethargy, 323, 324, 332 Leucine, 121, 257, 332 Leukemia, 258, 332 Leukocytes, 18, 107, 291, 293, 311, 319, 322, 326, 328, 332, 341 Library Services, 274, 332 Lice, 50, 332 Lidocaine, 26, 332 Life cycle, 54, 199, 332
Life Expectancy, 160, 332 Ligament, 332, 353, 363 Ligands, 160, 162, 165, 182, 328, 332 Ligation, 34, 332 Limbic, 285, 332 Limbic System, 285, 332 Linkage, 25, 29, 84, 332, 346 Lipid, 7, 43, 148, 150, 175, 198, 211, 218, 288, 289, 318, 327, 330, 333, 369 Lipid A, 148, 150, 333 Lipolysis, 80, 148, 333 Lipopolysaccharides, 333 Lipoprotein, 175, 188, 308, 333 Lithium, 288, 333 Liver Transplantation, 68, 333 Lobe, 96, 115, 287, 298, 333 Localization, 58, 162, 165, 333 Localized, 293, 320, 322, 326, 331, 333, 349, 366 Locomotion, 333, 349 Longitudinal Studies, 59, 303, 333 Longitudinal study, 53, 333 Loop, 50, 56, 328, 333 Low-density lipoprotein, 309, 333 Lumbar, 291, 333 Luteal Phase, 333, 337 Lymph, 56, 299, 310, 333, 334, 345 Lymph node, 56, 333, 334, 345 Lymphadenitis, 79, 334 Lymphatic, 56, 310, 326, 333, 334, 336, 362, 363, 367 Lymphatic system, 333, 334, 362, 363, 367 Lymphoblastic, 334 Lymphoblasts, 281, 334 Lymphocyte, 51, 281, 287, 334, 335 Lymphocyte Count, 281, 334 Lymphoid, 287, 334 Lymphoma, 86, 125, 258, 334 Lymphoproliferative, 334, 369 M Macrophage, 61, 300, 334 Macula, 334 Macula Lutea, 334 Macular Degeneration, 183, 334 Magnetic Resonance Imaging, 24, 29, 57, 334 Magnetic Resonance Spectroscopy, 99, 126, 334 Maintenance therapy, 84, 334 Malabsorption, 64, 186, 208, 258, 334 Malabsorption syndrome, 64, 334 Malaria, 85, 334, 335
386 Hypoglycemia
Malaria, Falciparum, 334, 335 Malaria, Vivax, 334, 335 Malignant, 59, 90, 96, 101, 105, 258, 281, 282, 288, 289, 293, 335, 339, 355, 366 Malnutrition, 155, 176, 180, 214, 284, 290, 335, 338 Mammary, 301, 335 Manic, 288, 333, 335, 354 Manic-depressive psychosis, 335, 354 Manifest, 64, 291, 335 Maternal Exposure, 33, 335 Meat, 267, 335 Meatus, 335, 370, 371 Medial, 53, 289, 335, 343 Mediate, 30, 33, 40, 52, 66, 68, 155, 181, 183, 308, 335 Mediator, 335, 360 Medical Records, 335, 358 Medicament, 335, 365 MEDLINE, 253, 257, 258, 335 Medullary, 40, 335, 340 Meiosis, 292, 335, 366 Melanin, 335, 348, 370 Melanocytes, 335, 336 Melanoma, 258, 336 Memantine, 164, 336 Membrane Glycoproteins, 336 Memory, 10, 29, 53, 57, 97, 105, 106, 278, 287, 305, 336 Meninges, 297, 303, 319, 336, 370 Menopause, 198, 214, 336, 350 Menstrual Cycle, 8, 198, 333, 336, 352 Menstruation, 284, 305, 333, 336 Mental Disorders, 139, 336, 354 Mental Health, iv, 14, 139, 252, 256, 336, 343, 354 Mental Processes, 307, 336, 354 Mesenchymal, 105, 336 Mesolimbic, 288, 336 Metabolic disorder, 318, 323, 336 Metabolite, 43, 336, 355 Metabotropic, 155, 181, 336 Metallothionein, 47, 336 Metastasis, 183, 336 Metastatic, 111, 293, 336, 359 Methionine, 336, 365 MI, 123, 142, 143, 146, 163, 179, 182, 197, 280, 336 Microbe, 337, 368 Microbiology, 53, 282, 337 Microdialysis, 7, 20, 35, 337 Microorganism, 300, 337, 372
Microscopy, 70, 291, 337 Middle Cerebral Artery, 7, 16, 337 Mifepristone, 44, 337 Migration, 183, 337, 340 Milligram, 9, 204, 337 Mineralocorticoids, 218, 282, 303, 337 Mitochondria, 54, 337 Mitochondrial Swelling, 337, 339 Mitosis, 289, 337, 362 Mobilization, 15, 63, 337 Modeling, 20, 27, 30, 31, 337 Modification, 121, 189, 317, 337, 355 Modulator, 34, 337 Molecular Structure, 195, 338, 369 Monitor, 4, 6, 32, 35, 75, 148, 151, 203, 254, 303, 338, 342 Monoclonal, 61, 323, 330, 338, 355, 373 Monocyte, 61, 338 Monotherapy, 18, 166, 338 Morphine, 147, 338, 339, 343 Morphological, 109, 310, 335, 338 Motility, 197, 326, 338, 360 Motion Sickness, 338, 339 Movement Disorders, 288, 338, 367 Mucus, 338, 370 Multidrug resistance, 58, 338 Muscimol, 26, 338 Muscle Fibers, 338 Muscular Atrophy, 258, 338 Muscular Dystrophies, 309, 338 Musculature, 338, 363 Myalgia, 327, 338 Myasthenia, 320, 338 Myocardial infarction, 17, 78, 208, 303, 336, 338 Myocardium, 336, 338 Myoclonus, 155, 180, 181, 339 Myopathy, 218, 339 Myotonic Dystrophy, 258, 339 N Naive, 166, 339 Narcotic, 338, 339 Nasal Mucosa, 327, 339 Nasogastric, 311, 339 Natural selection, 292, 339 Nausea, 8, 193, 210, 287, 288, 316, 326, 331, 339, 370 NCI, 1, 139, 251, 299, 339 Necrosis, 111, 289, 293, 297, 322, 326, 336, 338, 339, 357, 358 Neoplasia, 258, 339 Neoplasm, 104, 116, 339, 345
Index 387
Neoplastic, 323, 334, 339 Nerve, 44, 72, 160, 180, 187, 190, 197, 200, 206, 207, 210, 225, 228, 262, 282, 286, 290, 291, 305, 315, 316, 327, 335, 339, 340, 343, 347, 350, 352, 359, 363, 364, 369, 371 Nerve Endings, 180, 339 Nervousness, 263, 267, 340 Neural Pathways, 22, 340 Neural tube defects, 314, 340 Neuralgia, 214, 340 Neuroblastoma, 75, 340 Neurodegenerative Diseases, 142, 144, 146, 154, 160, 164, 180, 182, 183, 291, 340 Neuroeffector Junction, 339, 340 Neuroendocrine, 26, 30, 35, 39, 42, 44, 77, 82, 83, 104, 116, 340 Neuroendocrine tumor, 77, 340 Neuroendocrinology, 109, 218, 340 Neurogenic, 13, 340 Neuroglia, 317, 340 Neuroleptic, 284, 288, 340 Neurologic, 9, 98, 148, 155, 181, 229, 323, 340, 369 Neuromuscular, 225, 281, 340 Neuropeptides, 20, 341 Neuropharmacology, 23, 341 Neurophysiology, 122, 306, 341 Neuroprotective Agents, 142, 143, 163, 164, 182, 184, 341 Neuropsychological Tests, 5, 29, 341 Neuroretinitis, 341, 357 Neurosis, 341, 348 Neurosurgeon, 47, 341 Neurotoxicity, 330, 341 Neurotransmitters, 20, 35, 142, 143, 147, 163, 182, 184, 312, 341, 351, 362 Neutrons, 329, 341, 355 Neutrophils, 58, 319, 332, 341 Niacin, 122, 341, 369 Nicotine, 164, 341 Nifedipine, 100, 342 Nitric Oxide, 17, 342 Nitrogen, 34, 54, 168, 284, 286, 313, 318, 331, 342, 345, 369 Norepinephrine, 9, 17, 48, 101, 282, 308, 342 Nuclear, 54, 291, 309, 312, 332, 339, 342, 358, 367 Nuclei, 285, 287, 309, 317, 332, 334, 337, 341, 342, 344, 354
Nucleic acid, 156, 282, 317, 323, 326, 342, 363 Nucleic Acid Hybridization, 323, 342 Nucleotidases, 58, 342 Nucleus, 20, 26, 287, 289, 291, 299, 304, 309, 311, 312, 335, 341, 342, 352, 354, 362, 364, 367, 372 Nutrition Assessment, 228, 342 Nutritional Status, 17, 185, 199, 208, 342 Nutritional Support, 185, 316, 342 Nutritive Value, 314, 342 O Observational study, 56, 343 Occupational Health, 123, 343 Octreotide, 99, 105, 111, 241, 246, 343 Ocular, 164, 195, 200, 208, 343 Ointments, 343, 361 Oligoelement, 343 Oliguria, 331, 343 Oncogene, 51, 258, 343 Oncogenic, 328, 343 Opacity, 305, 343 Ophthalmic, 213, 343 Opium, 338, 343 Opportunistic Infections, 281, 343 Opsin, 343, 357 Optic Chiasm, 324, 343, 344 Optic Disk, 306, 334, 343 Optic Nerve, 341, 343, 357 Oral Health, 186, 187, 208, 344 Organizational Culture, 202, 344 Orgasm, 225, 344 Orthostatic, 288, 343, 344 Osmotic, 284, 337, 344 Osteoarthritis, 155, 181, 344 Osteoporosis, 183, 213, 219, 344 Outpatient, 211, 215, 344 Ovalbumin, 51, 344 Ovaries, 324, 344, 360, 366 Ovary, 319, 324, 344 Overdosage, 93, 344 Overdose, 99, 344 Ovulation, 333, 344, 358 Ovum, 304, 317, 332, 344, 352, 373 Oxalate, 142, 344 Oxidation, 23, 35, 44, 55, 63, 73, 281, 288, 304, 306, 321, 344 Oxidative metabolism, 283, 344 Oximetry, 21, 345 Oxygen Consumption, 313, 345, 357 Oxygenation, 50, 321, 345 Oxytocin, 115, 345
388 Hypoglycemia
P Palliative, 345, 367 Palsy, 162, 165, 345, 362 Pancreas Transplant, 59, 78, 190, 216, 237, 262, 345 Pancreas Transplantation, 59, 78, 190, 216, 237, 262, 345 Pancreatectomy, 59, 96, 115, 345 Pancreatic cancer, 258, 345 Pancreatic Insufficiency, 33, 345 Pancreatic Polypeptide, 9, 44, 345 Papilloma, 345, 358 Paralysis, 320, 345, 362 Parasite, 54, 345 Parasitic, 54, 332, 345 Parasitism, 54, 345 Parathyroid, 218, 345, 346, 367 Parathyroid Glands, 345, 346 Parenteral, 34, 146, 186, 208, 346 Parenteral Nutrition, 34, 186, 208, 346 Parkinsonism, 142, 143, 147, 163, 164, 182, 288, 346 Paroxysmal, 258, 320, 346 Particle, 346, 369 Patent ductus arteriosus, 101, 115, 346 Pathogenesis, 15, 39, 44, 55, 187, 189, 211, 213, 222, 224, 231, 346 Pathologic, 281, 289, 303, 324, 346, 357, 371 Pathologic Processes, 289, 346 Pathologies, 25, 346 Pathophysiology, 16, 23, 33, 46, 88, 92, 160, 165, 189, 199, 219, 222, 226, 227, 230, 233, 346 Patient Care Team, 190, 209, 346 Patient Compliance, 39, 346 Patient Education, 4, 69, 189, 191, 213, 226, 263, 264, 272, 274, 280, 346 Patient Selection, 189, 193, 346 Pelvic, 346, 353 Penicillin, 287, 346 Peptide Chain Elongation, 299, 346 Perception, 7, 23, 99, 231, 302, 347, 359 Perfusion, 318, 325, 347 Perinatal, 33, 62, 142, 143, 147, 163, 164, 182, 184, 203, 347 Periodontal disease, 205, 347 Peripheral Nervous System, 74, 295, 340, 345, 347, 351, 362, 365 Peripheral Neuropathy, 24, 187, 216, 237, 347 Peripheral Vascular Disease, 187, 208, 347 Peritoneal, 329, 347
Peritoneal Cavity, 329, 347 Perspiration, 4, 306, 347 Pesticides, 213, 327, 347 Phagocyte, 61, 347 Pharmaceutic Aids, 315, 347 Pharmacist, 218, 347 Pharmacologic, 15, 16, 34, 46, 194, 199, 286, 290, 347, 368 Pharmacotherapy, 18, 99, 100, 104, 347 Pharynx, 327, 348, 371 Phencyclidine, 48, 160, 348 Phenotype, 21, 54, 55, 64, 66, 316, 348 Phenylalanine, 348, 370 Phobia, 209, 348 Phobic Disorders, 348 Phospholipases, 348, 361 Phospholipids, 313, 327, 333, 348 Phosphorus, 186, 208, 294, 346, 348 Phosphorylate, 153, 348 Phosphorylation, 40, 58, 66, 68, 153, 156, 170, 179, 195, 348, 355 Physical Examination, 198, 200, 317, 348 Physical Fitness, 43, 348 Physiologic, 20, 36, 44, 56, 68, 81, 283, 292, 314, 336, 339, 348, 352, 356, 357, 366, 369 Pigment, 292, 335, 336, 343, 348 Piloerection, 324, 349 Pilot study, 60, 349 Piperidines, 164, 179, 349 Pituitary Gland, 162, 165, 218, 303, 349 Placenta, 12, 314, 349, 352 Placental Insufficiency, 32, 349 Placental tissue, 62, 349 Plants, 284, 289, 295, 300, 307, 317, 318, 319, 332, 342, 349, 359, 368 Plaque, 150, 349 Plasma cells, 287, 349 Plasma protein, 284, 349 Plasma Volume, 293, 337, 349 Plasticity, 53, 349 Platelet Activation, 349, 361 Platelet Aggregation, 342, 349 Platelets, 342, 349, 367 Platinum, 333, 349 Pleura, 90, 96, 111, 350 Poisoning, 50, 100, 155, 181, 305, 329, 339, 350 Polycystic, 174, 258, 324, 350 Polyethylene, 61, 350 Polymerase, 20, 350, 352 Polymerase Chain Reaction, 20, 350 Polymers, 114, 168, 350, 353
Index 389
Polypeptide, 153, 156, 179, 195, 285, 300, 314, 319, 323, 345, 350, 362, 370, 373 Polysaccharide, 173, 287, 297, 350, 353 Pontine, 78, 350 Portal Vein, 135, 350 Portosystemic Shunt, 87, 350 Posterior, 26, 286, 290, 291, 297, 298, 308, 345, 350, 363 Postmenopausal, 344, 350 Postnatal, 45, 52, 350 Postoperative, 102, 350 Postprandial, 9, 74, 101, 122, 166, 174, 226, 227, 231, 350 Postsynaptic, 155, 180, 181, 340, 350, 361, 365, 366 Post-translational, 59, 350 Post-traumatic, 162, 165, 320, 338, 351 Post-traumatic stress disorder, 162, 165, 351 Postural, 208, 351 Potassium, 20, 48, 52, 65, 156, 224, 308, 337, 351, 361 Potassium Channels, 52, 351 Potentiation, 59, 351, 361 Practice Guidelines, 256, 351 Praseodymium, 127, 351 Preclinical, 29, 351 Precursor, 35, 308, 309, 311, 319, 342, 348, 351, 363, 369, 370 Predisposition, 43, 351 Pregnancy in Diabetics, 306, 351 Pregnancy Outcome, 38, 41, 351 Pregnancy Tests, 317, 351 Pressoreceptors, 291, 351 Presynaptic, 38, 339, 340, 351, 365, 366 Presynaptic Terminals, 339, 351, 366 Prevalence, 28, 90, 101, 115, 211, 218, 351 Probe, 30, 49, 320, 337, 351 Problem Solving, 197, 210, 352 Procaine, 332, 352 Progeny, 25, 352 Progesterone, 337, 352, 364 Prognostic factor, 352, 365 Progression, 4, 11, 22, 43, 44, 68, 158, 171, 199, 286, 352, 370 Proinsulin, 105, 352, 355 Projection, 211, 305, 342, 344, 352, 356 Proline, 300, 323, 352 Promoter, 25, 34, 47, 51, 59, 352 Promotor, 352, 357 Prone, 36, 352 Prophase, 292, 352, 366
Prophylaxis, 164, 352 Prospective study, 333, 352 Prostaglandin, 286, 352 Prostaglandins A, 326, 353 Prostaglandins F, 337, 353 Prostate, 258, 353 Protease, 285, 301, 353 Protective Agents, 146, 294, 353 Protein C, 52, 61, 284, 285, 288, 291, 333, 353, 370 Protein S, 25, 146, 149, 161, 178, 223, 258, 259, 292, 299, 312, 317, 353, 358 Protein Transport, 52, 353 Proteinuria, 195, 353 Proteoglycans, 150, 291, 313, 353 Proteolytic, 63, 301, 314, 353 Protocol, 28, 32, 354 Protons, 323, 329, 334, 354, 355 Protozoa, 54, 337, 354, 369 Proximal, 51, 307, 331, 351, 354 Psychiatric, 9, 29, 41, 60, 162, 165, 207, 336, 354 Psychiatry, 30, 49, 57, 63, 354, 364 Psychic, 341, 354, 360 Psychology, 13, 26, 53, 196, 231, 307, 354 Psychomotor, 29, 295, 305, 340, 354 Psychosis, 48, 142, 143, 146, 147, 154, 163, 180, 182, 183, 288, 317, 354 Psychotherapy, 300, 354 Puberty, 188, 354 Public Health, 60, 206, 256, 354 Public Policy, 253, 354 Publishing, 3, 5, 8, 71, 186, 192, 203, 204, 207, 209, 227, 264, 266, 268, 354 Pulmonary, 91, 142, 143, 147, 163, 182, 184, 293, 294, 302, 308, 313, 331, 346, 354, 371 Pulmonary Artery, 293, 308, 346, 354, 372 Pulmonary Edema, 91, 331, 354 Pulse, 21, 151, 338, 345, 355 Purified Insulins, 352, 355 Purulent, 355, 371 Putrefaction, 316, 355 Pylorus, 308, 355 Pyridoxal, 322, 355 Pyridoxal Phosphate, 322, 355 Pyruvate Kinase, 47, 355 Q Quality of Life, 6, 32, 37, 69, 188, 201, 355 Quinolinic, 164, 355 Quinolinic Acid, 164, 355
390 Hypoglycemia
R Race, 330, 337, 355 Radiation, 282, 309, 311, 313, 314, 315, 328, 329, 335, 355, 373 Radiation therapy, 282, 313, 315, 328, 329, 355, 373 Radioactive, 323, 326, 328, 329, 342, 343, 355, 373 Radiography, 317, 355 Radiolabeled, 61, 330, 355, 373 Radiotherapy, 293, 330, 355, 373 Randomized, 7, 12, 27, 37, 71, 73, 74, 93, 309, 356 Rape, 351, 356 Reaction Time, 7, 356 Reagent, 149, 178, 285, 323, 356 Reality Testing, 354, 356 Receptors, Serotonin, 356, 360 Recombinant, 39, 54, 93, 149, 178, 356, 371 Rectum, 293, 300, 307, 314, 316, 326, 327, 331, 353, 356, 365 Red Nucleus, 290, 356 Refer, 1, 137, 301, 308, 333, 334, 339, 340, 341, 354, 356 Reflux, 152, 356 Refraction, 356, 363 Regimen, 6, 11, 53, 90, 94, 148, 159, 196, 206, 213, 309, 346, 347, 356 Regurgitation, 320, 356 Rehydration, 186, 356 Reliability, 70, 158, 356 Remission, 334, 335, 356 Renal failure, 175, 305, 356 Reperfusion, 46, 49, 82, 356, 357 Reperfusion Injury, 357 Reproduction Techniques, 351, 357 Research Design, 29, 357 Resection, 101, 357 Resorption, 323, 357 Respiration, 33, 295, 298, 338, 357 Respiratory Therapy, 34, 357 Response Elements, 34, 357 Restoration, 49, 356, 357, 373 Resuscitation, 203, 310, 357 Retina, 65, 167, 298, 299, 306, 334, 340, 341, 343, 344, 357, 358, 372 Retinal, 61, 66, 164, 302, 306, 343, 344, 357 Retinitis, 142, 143, 146, 147, 154, 163, 180, 182, 295, 357, 358 Retinitis Pigmentosa, 295, 358 Retinoblastoma, 68, 258, 358 Retinoblastoma Protein, 68, 358
Retinoid, 152, 358 Retinol, 357, 358 Retinopathy, 69, 148, 164, 172, 197, 201, 207, 216, 228, 306, 358 Retrograde, 22, 358 Retrospective, 42, 57, 105, 358 Retrospective study, 105, 358 Retroviral vector, 39, 358 Retrovirus, 39, 358 Rhabdomyolysis, 73, 358 Rheumatism, 358 Rheumatoid, 106, 183, 358 Rheumatoid arthritis, 106, 183, 358 Rhythm Method, 203, 358 Ribose, 282, 358 Ribosome, 358, 369 Rigidity, 346, 349, 358 Rod, 299, 358 Rodenticides, 347, 358 Rosiglitazone, 166, 359 S Salicylate, 359, 362 Salicylic, 359 Salicylic Acids, 359 Saline, 231, 359 Salivary, 307, 345, 359 Salivary glands, 307, 359 Saponins, 359, 364 Satellite, 11, 359 Satiation, 31, 359 Schizoid, 359, 373 Schizophrenia, 155, 164, 180, 181, 183, 359, 373 Schizotypal Personality Disorder, 359, 373 Sclerosis, 144, 146, 147, 154, 155, 160, 162, 164, 165, 176, 180, 181, 182, 258, 289, 359 Screening, 56, 93, 104, 116, 149, 153, 169, 170, 178, 179, 193, 203, 299, 359 Second Messenger Systems, 341, 359 Secondary tumor, 336, 359 Secretory, 16, 30, 40, 59, 136, 340, 360, 365, 366 Seizures, 18, 20, 45, 57, 76, 77, 91, 155, 168, 181, 193, 267, 279, 295, 305, 311, 346, 360, 363 Self Administration, 9, 360 Self Care, 53, 187, 198, 202, 205, 206, 209, 228, 360 Sella, 349, 360 Semen, 353, 360 Semicircular canal, 327, 360 Semisynthetic, 299, 360
Index 391
Senile, 176, 344, 360 Sensor, 7, 20, 50, 56, 61, 70, 80, 328, 360 Sepsis, 34, 227, 360 Sequencing, 350, 360, 366 Serotonin, 21, 96, 288, 292, 347, 356, 360, 369 Serous, 301, 310, 350, 360 Sex Characteristics, 282, 286, 354, 360 Sex Determination, 258, 360 Sexually Transmitted Diseases, 210, 213, 360 Shock, 21, 34, 107, 277, 315, 339, 360, 369 Side effect, 18, 27, 144, 148, 166, 191, 209, 215, 245, 283, 284, 288, 292, 324, 360, 368 Signal Transduction, 15, 40, 64, 149, 160, 178, 327, 361 Signs and Symptoms, 24, 192, 196, 197, 232, 265, 356, 361 Skeletal, 25, 80, 286, 299, 338, 358, 361, 362 Skeleton, 323, 330, 352, 361 Skin Care, 201, 207, 214, 361 Skull, 303, 340, 361, 366 Sleep apnea, 361, 364 Small intestine, 64, 299, 308, 311, 323, 328, 339, 361, 372 Smooth muscle, 150, 290, 294, 302, 322, 338, 353, 361, 362, 365 Soaps, 361 Social Environment, 355, 361 Sodium, 48, 114, 116, 202, 203, 214, 255, 308, 337, 361, 362, 365, 371 Sodium Channels, 361, 371 Sodium salicylate, 114, 116, 362 Soft tissue, 293, 320, 361, 362 Solid tumor, 286, 362 Solitary Nucleus, 290, 362 Solvent, 281, 312, 318, 344, 362 Somatic, 282, 310, 332, 335, 337, 347, 362, 371 Somatostatin, 77, 94, 343, 362 Somatotropin, 328, 362 Sorbitol, 195, 362 Spasm, 147, 150, 154, 180, 182, 303, 362, 367 Spastic, 330, 362 Spasticity, 164, 362 Spatial disorientation, 308, 362 Specialist, 188, 206, 213, 269, 307, 362 Specificity, 21, 58, 112, 283, 295, 363 Spectrum, 5, 162, 165, 176, 206, 363 Spermidine, 363 Spermine, 66, 363
Spinal Cord Ischemia, 160, 363 Spinal Nerves, 347, 363 Spleen, 334, 345, 363 Splenectomy, 80, 363 Spontaneous Abortion, 351, 363 Sporadic, 340, 358, 363 Sprains and Strains, 210, 363 Standard therapy, 241, 363 Status Epilepticus, 57, 111, 142, 143, 147, 163, 182, 184, 363 Steatosis, 314, 321, 363 Steel, 299, 363 Sterile, 345, 363 Sterility, 327, 363 Sterilization, 203, 364 Steroid, 44, 303, 359, 364 Stillbirth, 351, 364 Stimulant, 285, 294, 322, 364 Stimulus, 65, 161, 308, 309, 312, 327, 329, 331, 348, 356, 364, 367 Stomatitis, 317, 364 Stool, 326, 330, 331, 364 Strand, 350, 364 Structure-Activity Relationship, 48, 364 Strychnine, 180, 364 Stupor, 42, 332, 339, 364 Subacute, 46, 326, 364 Subarachnoid, 320, 329, 364 Subclinical, 326, 360, 364 Subcutaneous, 7, 37, 50, 79, 99, 107, 159, 254, 282, 309, 346, 364 Subiculum, 322, 364 Subspecies, 362, 364 Substance P, 312, 336, 359, 365 Substrate, 23, 35, 44, 50, 63, 227, 365, 370 Sudden death, 17, 95, 365 Sulfur, 118, 168, 313, 336, 365 Supplementation, 7, 24, 32, 99, 116, 122, 126, 135, 203, 365 Support group, 189, 365 Suppositories, 116, 316, 365 Suppression, 15, 35, 40, 89, 162, 165, 170, 233, 303, 365 Survival Analysis, 27, 365 Sweat, 324, 347, 365 Sympathetic Nervous System, 286, 290, 365 Sympathomimetic, 285, 308, 311, 342, 365, 370 Symphysis, 353, 365 Symptomatic, 7, 19, 55, 96, 97, 98, 107, 127, 174, 306, 351, 365
392 Hypoglycemia
Symptomatology, 23, 365 Synapses, 65, 340, 341, 365, 366 Synapsis, 366 Synaptic, 33, 52, 65, 155, 181, 341, 361, 365, 366 Synaptic Transmission, 65, 155, 181, 341, 366 Synaptic Vesicles, 365, 366 Synchrony, 33, 366 Syncope, 17, 58, 129, 366 Systemic, 19, 20, 82, 108, 137, 219, 227, 231, 246, 288, 293, 305, 311, 326, 329, 355, 364, 366, 371, 373 Systolic, 324, 366 T Tachycardia, 159, 366 Tardive, 164, 288, 366 Telangiectasia, 258, 366 Temporal, 31, 53, 285, 320, 322, 334, 335, 366 Temporal Lobe, 285, 366 Teratoma, 77, 366 Testicles, 366 Tetani, 366 Tetanic, 366 Tetanus, 65, 366, 367 Tetany, 346, 367 Thalamic, 290, 367 Thalamic Diseases, 290, 367 Thalamus, 26, 293, 306, 332, 367 Theophylline, 81, 110, 240, 367 Therapeutics, 56, 69, 81, 88, 93, 95, 96, 108, 109, 110, 247, 367 Thermal, 32, 307, 341, 350, 367 Third Ventricle, 289, 324, 367 Thoracic, 291, 350, 367, 373 Thorax, 333, 367, 371 Threshold, 14, 36, 42, 112, 312, 324, 367 Thrombin, 314, 349, 353, 367 Thromboembolism, 327, 367 Thrombomodulin, 353, 367 Thrombosis, 150, 328, 329, 353, 364, 367 Thrombus, 151, 303, 326, 330, 349, 367 Thymus, 325, 334, 367 Thyroid, 74, 188, 218, 219, 324, 340, 345, 346, 368, 370 Thyroid Gland, 218, 345, 346, 368 Thyroid Hormones, 368, 370 Thyroxine, 284, 348, 368 Tin, 8, 193, 212, 347, 349, 368 Tolazamide, 150, 368
Tolerance, 24, 38, 41, 48, 50, 51, 62, 116, 142, 143, 146, 147, 152, 153, 163, 164, 168, 175, 180, 182, 183, 193, 197, 198, 224, 279, 281, 306, 318, 351, 368 Tooth Preparation, 282, 368 Topical, 193, 206, 312, 361, 368 Total pancreatectomy, 345, 368 Toxic, iv, 29, 59, 68, 107, 150, 304, 307, 311, 319, 322, 325, 335, 341, 368, 370 Toxicity, 56, 164, 308, 368 Toxicology, 114, 123, 254, 368 Toxins, 21, 287, 295, 310, 326, 368 Toxoid, 65, 368 Trace element, 114, 116, 175, 186, 208, 299, 368 Trachea, 294, 331, 348, 368 Traction, 299, 368 Transcriptase, 358, 368 Transcription Factors, 357, 368 Transduction, 37, 39, 361, 368 Transfection, 292, 369 Transient Ischemic Attacks, 58, 369 Translation, 60, 312, 369 Translational, 56, 369 Translocation, 299, 312, 353, 369 Transmitter, 52, 281, 290, 308, 312, 329, 335, 340, 342, 365, 366, 369, 370 Transplantation, 59, 138, 190, 194, 195, 215, 216, 237, 240, 299, 310, 325, 369 Tremor, 159, 174, 346, 369 Tricyclic, 191, 369 Trigger zone, 288, 369 Triglyceride, 175, 204, 324, 369 Troglitazone, 111, 166, 369 Trypanosome, 54, 369 Tryptophan, 300, 355, 360, 369 Tuberculosis, 302, 359, 369 Tuberous Sclerosis, 258, 369 Tumor Lysis Syndrome, 105, 369 Tumor model, 51, 369 Tumor suppressor gene, 358, 370 Tympanic membrane, 32, 370 Type 2 diabetes, 4, 5, 9, 14, 24, 25, 40, 85, 90, 92, 94, 95, 103, 108, 110, 146, 166, 189, 191, 193, 195, 197, 199, 201, 203, 205, 207, 211, 213, 217, 227, 228, 240, 370 Tyramine, 292, 370 Tyrosine, 153, 179, 308, 370 Tyrothricin, 319, 370 U Ulcerative colitis, 145, 327, 370 Ultrasonography, 203, 317, 370
Index 393
Unconscious, 148, 266, 286, 305, 325, 370 Urea, 166, 331, 365, 370 Uremia, 331, 356, 370 Ureters, 331, 370 Urethra, 353, 370 Urinary tract, 210, 370 Urinary tract infection, 210, 370 Urine Testing, 197, 207, 371 Uterine Contraction, 345, 371 Uterus, 33, 285, 305, 310, 336, 344, 352, 371 V Vaccine, 65, 282, 354, 371 Vagal, 66, 371 Vagina, 336, 371 Vaginitis, 210, 371 Vagus Nerve, 18, 362, 371 Valproic Acid, 18, 371 Vascular endothelial growth factor, 15, 72, 112, 371 Vascular Resistance, 291, 371 Vasculitis, 298, 371 Vasoconstriction, 311, 371 Vasodilator, 288, 293, 308, 322, 342, 371 Vasogenic, 46, 371 Vector, 39, 149, 153, 178, 179, 369, 371 Vegetarianism, 213, 371 Vein, 289, 329, 342, 350, 359, 371 Venous, 20, 37, 70, 289, 293, 298, 305, 329, 353, 371 Venous blood, 293, 298, 371 Ventral, 35, 289, 324, 363, 371 Ventricle, 285, 322, 354, 355, 366, 367, 371, 372 Ventricular, 323, 366, 372 Ventromedial Hypothalamic Nucleus, 37, 372 Venules, 293, 295, 372 Vertebrae, 363, 372
Vesicular, 353, 372 Vestibule, 300, 327, 360, 372 Veterinary Medicine, 114, 253, 372 Villi, 323, 372 Viral, 55, 314, 327, 343, 358, 368, 372 Virilism, 324, 372 Virulence, 290, 368, 372 Virus, 47, 147, 162, 165, 182, 281, 291, 297, 311, 317, 319, 328, 349, 358, 369, 372 Visceral, 290, 291, 332, 371, 372 Visceral Afferents, 290, 371, 372 Vitamin A, 185, 191, 203, 208, 327, 358, 372 Vitreous Body, 298, 357, 372 Vitreous Hemorrhage, 306, 372 Vitro, 25, 61, 372 Vivo, 25, 31, 33, 44, 47, 61, 372 Voltage-gated, 48, 372 Vomica, 364, 372 W War, 351, 372 Weight Gain, 189, 191, 203, 313, 372 Weight-Bearing, 344, 372 White blood cell, 18, 57, 281, 287, 301, 326, 332, 334, 338, 349, 373 Windpipe, 348, 368, 373 Withdrawal, 142, 143, 146, 147, 162, 163, 164, 165, 180, 182, 305, 373 Womb, 371, 373 Wound Healing, 328, 373 X Xenograft, 286, 370, 373 X-ray, 145, 314, 329, 342, 355, 373 X-ray therapy, 330, 373 Y Yeasts, 348, 373 Z Zygote, 302, 373 Zymogen, 353, 373
394 Hypoglycemia
Index 395
396 Hypoglycemia
