DIABETIC
RETINOPATHY A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES
J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS
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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright 2004 by ICON Group International, Inc. Copyright 2004 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1
Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Diabetic Retinopathy: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-497-00355-4 1. Diabetic Retinopathy-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 diabetic retinopathy. 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 DIABETIC RETINOPATHY .......................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Diabetic Retinopathy................................................................... 12 E-Journals: PubMed Central ....................................................................................................... 70 The National Library of Medicine: PubMed ................................................................................ 70 CHAPTER 2. NUTRITION AND DIABETIC RETINOPATHY .............................................................. 115 Overview.................................................................................................................................... 115 Finding Nutrition Studies on Diabetic Retinopathy ................................................................. 115 Federal Resources on Nutrition ................................................................................................. 117 Additional Web Resources ......................................................................................................... 117 CHAPTER 3. ALTERNATIVE MEDICINE AND DIABETIC RETINOPATHY ........................................ 119 Overview.................................................................................................................................... 119 National Center for Complementary and Alternative Medicine................................................ 119 Additional Web Resources ......................................................................................................... 122 General References ..................................................................................................................... 123 CHAPTER 4. DISSERTATIONS ON DIABETIC RETINOPATHY .......................................................... 125 Overview.................................................................................................................................... 125 Dissertations on Diabetic Retinopathy ...................................................................................... 125 Keeping Current ........................................................................................................................ 125 CHAPTER 5. PATENTS ON DIABETIC RETINOPATHY ..................................................................... 127 Overview.................................................................................................................................... 127 Patents on Diabetic Retinopathy ............................................................................................... 127 Patent Applications on Diabetic Retinopathy............................................................................ 131 Keeping Current ........................................................................................................................ 141 CHAPTER 6. BOOKS ON DIABETIC RETINOPATHY ........................................................................ 143 Overview.................................................................................................................................... 143 Book Summaries: Federal Agencies............................................................................................ 143 Chapters on Diabetic Retinopathy ............................................................................................. 144 CHAPTER 7. MULTIMEDIA ON DIABETIC RETINOPATHY .............................................................. 147 Overview.................................................................................................................................... 147 Video Recordings ....................................................................................................................... 147 CHAPTER 8. PERIODICALS AND NEWS ON DIABETIC RETINOPATHY ........................................... 149 Overview.................................................................................................................................... 149 News Services and Press Releases.............................................................................................. 149 Newsletter Articles .................................................................................................................... 151 Academic Periodicals covering Diabetic Retinopathy................................................................ 152 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 155 Overview.................................................................................................................................... 155 NIH Guidelines.......................................................................................................................... 155 NIH Databases........................................................................................................................... 157 Other Commercial Databases..................................................................................................... 159 APPENDIX B. PATIENT RESOURCES ............................................................................................... 161 Overview.................................................................................................................................... 161 Patient Guideline Sources.......................................................................................................... 161 Finding Associations.................................................................................................................. 165 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 167 Overview.................................................................................................................................... 167 Preparation................................................................................................................................. 167 Finding a Local Medical Library................................................................................................ 167
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Medical Libraries in the U.S. and Canada ................................................................................. 167 ONLINE GLOSSARIES................................................................................................................ 173 Online Dictionary Directories ................................................................................................... 174 DIABETIC RETINOPATHY DICTIONARY ............................................................................ 175 INDEX .............................................................................................................................................. 241
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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 diabetic retinopathy 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 diabetic retinopathy, 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 diabetic retinopathy, 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 diabetic retinopathy. 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 diabetic retinopathy, 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 diabetic retinopathy. 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 DIABETIC RETINOPATHY Overview In this chapter, we will show you how to locate peer-reviewed references and studies on diabetic retinopathy.
The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and diabetic retinopathy, 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 “diabetic retinopathy” (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: •
Diabetic Retinopathy: A Clinical Overview Source: Diabetes Care. 15(12): 1844-1874. December 1992. Summary: After an introductory summary, this review article describes the natural course of diabetic retinopathy, then briefly considers selected pathogenetic and epidemiological concepts. A discussion of current treatment concludes the article. Specific topics include diabetic retinopathy and blood glucose control; the classification of retinopathy; and treatment modalities, including antiplatelet agents, photocoagulation, and vitrectomy. 24 figures. 7 tables. 146 references. (AA-M).
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Diabetic Retinopathy
Anemia: A Risk Factor for Diabetic Retinopathy? Source: Practical Diabetology. 20(4): 32-34. December 2001. Contact: Available from R.A. Rapaport Publishing, Inc. 150 West 22nd Street, New York, NY 10011. (212) 989-0200 or (773) 777-6801. Summary: Diabetic retinopathy (eye disease associated with diabetes) continues to be a major problem in the United States. This article reviews the risk factors for diabetic retinopathy and then presents a case report that supports the idea that anemia needs to be added to the list of risk factors. Retinal hypoxia (reduced amounts of oxygen being delivered to the retina) has long been associated with the development of diabetic retinopathy; anemia is one of the conditions that can contribute to retinal hypoxia. The authors discuss the clinical features, mechanism of injury from anemia, and relationship between retinopathy and hemoglobin level. The authors conclude by suggesting laboratory evaluation for anemia in patients with diabetes who may have an increased risk of developing anemia. This group includes pregnant women, women with menorrhagia (loss of large amounts of blood with their menstruation), postoperative patients, patients with renal (kidney) failure, patients with neoplastic processes (including cancer), patients with gastrointestinal bleeding, and patients with poor blood glucose control. Normalization of hemoglobin levels may stabilize progressive retinopathy. 9 references.
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Exercise for Patients with Diabetic Retinopathy (commentary) Source: Diabetes Care. 18(1): 130-132. January 1995. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: In this article about diabetic retinopathy and exercise, the authors stress the importance of developing exercise prescriptions for individuals who have proliferative diabetic retinopathy (PDR) and other concurrent diabetic complications to improve their participation in normal daily activities and psychosocial well being, while minimizing the risk of further visual deterioration. The authors describe a research study that investigated diabetes education, psychosocial support, and exercise for diabetes patients with visual impairment. They also discuss balancing risk factors with the potential benefits of exercise; special adaptations in exercise programs; and concerns that exercise will precipitate a vitreoretinal hemorrhage. 10 references.
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Current Therapy of Diabetic Retinopathy: Laser and Vitreoretinal Surgery Source: Journal of the National Medical Association. 85(11): 841-847. November 1993. Summary: In this article, the author reviews the pathophysiology of diabetic retinopathy, delineates the types of diabetic retinopathy, and outlines treatment and management options. Specific topics include nonproliferative diabetic retinopathy (background), preproliferative diabetic retinopathy, proliferative diabetic retinopathy (PDR), management recommendations for each type of retinopathy, the use of laser photocoagulation, vitreous surgery, the indications and patient selection for these surgeries, and the prognosis for diabetic vitrectomized eyes. The author stresses that early detection and diagnosis of diabetic retinopathy will lead to earlier treatment and prevention of loss of sight. 5 figures. 2 tables. 11 references.
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How Effective Are Treatments for Diabetic Retinopathy? (commentary) Source: JAMA. Journal of the American Medical Association. 269(10): 1290-1291. March 10, 1993. Summary: In this article, the author summarizes recent research projects that demonstrate the overall effectiveness of early identification and treatment of proliferative diabetic retinopathy (PDR) in preventing blindness. Clinical trials discussed include the Diabetic Retinopathy Study (DRS), the Diabetic Retinopathy Vitrectomy Study (DRVS), and the Early Treatment Diabetic Retinopathy Study (ETDRS). The author stresses that the data from these studies, demonstrating that use of the currently recommended treatment strategies strikingly reduces the risk of blindness for patients with PDR, make full implementation of recommended treatments for diabetic retinopathy all the more imperative. The author concludes with a brief discussion of two preventive programs now being implemented and the need for professionals to support and participate in these programs. 1 figure. 12 references. (AAM).
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C-Peptide and the Classification of Diabetes Mellitus Patients in the Early Treatment Diabetic Retinopathy Study: Report Number 6 Source: Annals of Epidemiology. 3(1): 9-17. January 1993. Summary: The Early Treatment Diabetic Retinopathy Study (ETDRS), conducted at 22 clinical centers during the period 1980 to 1989, collected baseline data on C-peptide levels after ingestion of Sustacal in 582 patients with diabetes mellitus prior to enrollment in the trial. Data on several clinical factors associated with diabetes were also collected from all 3711 enrolled patients. This article describes how the C-peptide data were used to develop sets of clinical criteria for the classification of ETDRS patients and to compare and contrast definitions of type of diabetes used in previous studies. The authors conclude that a comparison of these previous studies revealed that even in the absence of C-peptide data, clinically derived definitions provided good discrimination between insulin-dependent and noninsulin-dependent diabetes. 5 tables. 35 references.
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Diabetes and Diabetic Retinopathy in a Mexican-American Population Source: Diabetes Care. 24(7): 1204-1209. July 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 determined the prevalence rates of diabetes and diabetic retinopathy (DR) in a population based study, Proyecto VER (Vision Evaluation and Research), of Hispanics aged 40 years or older residing in Pima and Santa Cruz counties in Arizona. The study population consisted of 4,774 people who completed the examinations. Diabetes was defined as self report of a physician diagnosis or a glycosylated hemoglobin (HbA1c) value of 7 percent or more. DR was assessed on stereo fundus photographs of fields 1, 2, and 4. The study found that the prevalence of diabetes in the Hispanic community was 22 percent. The prevalence rate of DR was 48 percent, with 32 percent having moderate to severe nonproliferative and proliferative retinopathy. DR increased with increasing duration of diabetes and increasing level of HbA1c. The prevalence rate of DR like changes in the sample of individuals without diabetic retinopathy was 15 percent and was not associated with hypertension, systolic blood pressure, or diastolic blood pressure. The article concludes that the prevalence rate of diabetes in this population of Hispanics is high, almost twice
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Diabetic Retinopathy
that of Caucasians. The prevalence rate of DR is high but similar to reports in a Caucasian population. The prevalence rate of 9 percent moderate to severe retinopathy in the newly diagnosed group suggests that efforts to improve detection and treatment of diabetes in Hispanics may be warranted. 2 figures. 5 tables. 25 references. (AA-M). •
Results of 20 Years of Research on the Treatment of Diabetic Retinopathy Source: Preventive Medicine. 23(5): 740-742. September 1994. Contact: Available from Academic Press, Inc. 6277 Sea Harbor Drive, Orlando, FL 328874900. Summary: This article describes four different multicenter randomized clinical trials on the treatment of diabetic retinopathy that were supported by the National Eye Institute. The trials include the Diabetic Retinopathy Study (DRS), the Diabetic Retinopathy Vitrectomy Study (DRVS), the Sorbinil Retinopathy Trial, and the Early Treatment Diabetic Retinopathy Study (ET DRS). The author summarizes treatment recommendations based on these four trials. Scatter treatment should be deferred for eyes with mild or moderate nonproliferative diabetic retinopathy; to be considered again as the retinopathy progresses to the severe nonproliferative or early proliferative stages. Scatter photocoagulation should be performed for virtually all eyes with highrisk proliferative retinopathy. Early vitrectomy should be considered for advanced active proliferative diabetic retinopathy. Finally, and most importantly, all patients with diabetic retinopathy should receive careful follow-up. The author concludes that implementing the results from these clinical trials can markedly reduce the risk of blindness. 14 references. (AA-M).
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Management of Diabetic Retinopathy Source: American Family Physician. 51(4): 785-796. March 1995. Summary: This article for primary care physicians discusses diabetic retinopathy and its management. The author describes the two stages of retinopathy: the nonproliferative stage, which includes intraretinal microaneurysms, hemorrhages, and soft and hard exudates; and the proliferative stage, which is characterized by neovascularization and fibrovascular growth from the retina or optic nerve. Other topics covered include macular edema, complications that lead to blindness, the role of good glycemic control in reducing the development of retinopathy, the role of hypertension control, the importance of regular ophthalmologic examinations, and laser treatments. 14 figures. 2 tables. 23 references. (AA-M).
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Diabetic Retinopathy: The Primary Care Physician's Role in Management Source: Postgraduate Medicine. 91(5): 141-144, 147, 150, 155-158. April 1992. Summary: This article presents guidelines for the primary care physician's role in the management of diabetic retinopathy. Topics include the primary care evaluation of patients with diabetes, causes of visual loss in patients with diabetes, the types of diabetic retinopathy, and treatment modalities, including photocoagulation and vitrectomy. Types of retinopathy described are background retinopathy, including retinal edema, microaneurysms, retinal hemorrhages, cotton-wool spots, and intraretinal vascular changes; and proliferative retinopathy, including neovascularization, new vessel hemorrhage, and tractional retinal detachment. The author also reports on a recent socioeconomic study that investigated the cost of screening all patients with
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diabetes for significant retinopathy and the cost for treating the expected incidence of vision-threatening retinopathy. (AA-M). •
Aspirin Effects on Mortality and Morbidity in Patients With Diabetes Mellitus: Early Treatment Diabetic Retinopathy Study Report 14 Source: JAMA. Journal of American Medical Association. 268(10): 1292-1300. September 9, 1992. Summary: This article presents information on the effects of aspirin on mortality, the occurrence of cardiovascular events, and the incidence of kidney disease in the patients enrolled in the Early Treatment Diabetic Retinopathy Study (ETDRS). Patients (n=3711) were enrolled in 22 clinical centers between April 1980 and July 1985. Men and women between the ages of 18 and 70 years with a clinical diagnosis of diabetes mellitus were eligible. Patients were randomly assigned to aspirin or placebo (two 325-mg tablets once per day). Results show that the effects of aspirin on any of the cardiovascular events considered in the ETDRS were not substantially different from the effects observed in other studies that included mainly nondiabetic persons. The ETDRS results support recommending aspirin for persons with diabetes at increased risk of cardiovascular disease. 2 figures. 7 tables. 35 references. (AA-M).
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Screening for Diabetic Retinopathy in Communities Source: Diabetes Educator. 18(2): 115-120. March-April 1992. Summary: This article reports on 12 retinopathy screening clinics, serving 489 patients with diabetes, that were conducted in 3 Michigan communities as part of an outreach effort. Screening activities were initiated by local diabetes educators who conducted a program designed to promote detection of diabetic eye disease and increase patient and health care provider awareness of accepted ophthalmic evaluation guidelines. The authors stress that three factors suggest that retinopathy screening clinics can be successfully conducted: if health care professionals in the community consider diabetic retinopathy to be a serious problem; if one individual is willing to oversee the organizational aspects of the clinic; and if an ophthalmologist with laser treatment capability is present or nearby. 4 tables. 10 references. (AA-M).
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Role of Growth Hormone in the Development of Diabetic Retinopathy Source: Diabetes Care. 17(6): 531-534. June 1994. 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 research study undertaken to determine the role of growth hormone (GH) in the development of diabetic retinopathy. In this study, the medical records of 1,423 patients who had undergone insulin tolerance tests at the Mayo Clinic were examined, and diabetic subjects) were identified as either GH deficient or GH sufficient. Prevalence of retinopathy was determined in these cases and in a cohort group of diabetic subjects selected to match the GH deficient cases. Despite comparable age, duration of diabetes, and metabolic control, the prevalence of diabetic retinopathy in the GH deficient group was less that that observed in the GH sufficient group. Prevalence in the GH deficient group also was lower than that observed in the cohort control group. The authors conclude that these data strongly suggest that GH contributes to the development of diabetic retinopathy in humans. 1 figure. 1 table. 26 references. (AA-M).
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Screening for Diabetic Retinopathy Source: Annals of Internal Medicine. 116(8): 660-671. April 15, 1992. Summary: This article reports on a review of the literature designed to determine the appropriate patients, methods, and timing for screening for diabetic retinopathy. Relevant articles were identified through prominent review articles, the authors' files, recommendations from experts, and a MEDLINE search (1986 to the present); additional references were selected from the bibliographies of identified articles. After analyzing the data in the literature, the authors conclude that screening for retinopathy is justifiable if early detection leads to less vision loss at an acceptable cost. Topics include laser therapy, notably photocoagulation therapy; duration of diabetes as the main risk factor for retinopathy; the use of standard ophthalmologic examination versus sevenfield stereo-photography; and cost-effectiveness of screening programs. 3 figures. 2 tables. 74 references. (AA-M).
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Self-Rated Health and Diabetes of Long Duration: The Wisconsin Epidemiologic Study of Diabetic Retinopathy Source: Diabetes Care. 21(2): 236-240. February 1998. 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 designed to evaluate the self reported quality of life in people with diabetes of long duration. The authors point out that many studies of self-rated health have found that individuals with diabetes score lower than individuals who do not have diabetes. Participants in the study included two cohorts of people with diabetes who had been followed in an epidemiological study periodically since 1980. Researchers assessed their responses using measures of self-rated health from the Medical Outcomes Study Short Form 36. According to the results of the study, physical function, physical role, general health scales, and a general question about health were related to diabetes characteristics in older-onset and younger-onset individuals. In both younger-onset and older-onset individuals, symptoms of sensory neuropathy were associated with these four measures. Other descriptive variables in the younger-onset group were the presence of nephropathy, cardiovascular disease, smoking, peak expiratory flow, physical activity, and glycosylated hemoglobin. Hypoglycemic reactions were of borderline significance for one scale (physical role). Cardiovascular disease, physical activity, and sex were descriptive of responses to the quality of life questions in older-onset individuals. The authors conclude that factors related to diabetes contribute to self-assessed health. Some of these factors may be modifiable and may lead to improved quality of life if altered. 5 tables. 22 references. (AA-M).
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Is There an Ethnic Difference in the Effect of Risk Factors for Diabetic Retinopathy? Source: Annals of Epidemiology. 3(1): 2-8. January 1993. Summary: This article reports on a study in which researchers compare the effect of established risk factors between Caucasians with diabetes (n=478) and MexicanAmericans with diabetes (n=231). The authors hypothesize that, in Mexican-Americans with diabetes, established risk factors may have a stronger effect on diabetic retinopathy, compared to Caucasians with diabetes. Retinopathy was classified into two categories (any or none) as assessed by seven standard stereoscopic retinal photographs. The Mexican-Americans had an increased prevalence of any retinopathy. Longer
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duration of diabetes, more severe glycemia, earlier age at diagnosis, and insulin therapy were associated with diabetic retinopathy in both Mexican-Americans and Caucasians. These findings suggest that a differential effect of risk factors in these two groups does not explain the higher prevalence of retinopathy complications in the MexicanAmerican group. 3 tables. 39 references. (AA-M). •
Opportunities for Cost Reduction in Diabetic Retinopathy Treatment: Case Study from Mexico Source: Bulletin of the Pan American Health Organization. 28(1): 50-61. March 1994. Summary: This article reports on a study performed to explore the costs of treating diabetic retinopathy at a large eye hospital in Mexico, in order to identify opportunities for improving efficiency. Clinical records of a random sample of 69 patients with diabetes were reviewed for data on each patient's background, medical history, and treatment; the costs of all resources utilized in each type of procedure provided were documented and priced. The resulting data on clinical costs was complemented by data on the private costs of treatment (medical fees, accommodation costs, transportation costs, and lost wages) that were gathered from patient interviews. Results showed that the patients, who were generally poor, shouldered a substantial economic burden associated with treatment at the hospital; however, less than half this burden was in the form of fees. The authors give suggestions for reducing of these costs without endangering treatment quality. 5 tables. 13 references. (AA-M).
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Diabetic Retinopathy in Oklahoma Indians With NIDDM: Incidence and Risk Factors Source: Diabetes Care. 15(11): 1620-1627. November 1992. Summary: This article reports on a study to determine the incidence rates and risk factors for diabetic retinopathy in Oklahoma Indians. The researchers performed a cohort followup study with baseline examination between 1972 and 1980 and followup examination between 1987 and 1991 (mean follow-up time was 12.8 years). Study participants included a quasi-random sample of 1,012 Native Americans (379 men, 633 women) who had noninsulin-dependent diabetes mellitus (NIDDM) with a duration of 6.9 years at baseline. At follow-up, 515 (55.6 percent) were alive, 408 (44 percent) were deceased, and 4 (0.4 percent) could not be traced. Results show that the incidence of retinopathy among the participants who were free of disease at baseline and who survived the followup interval was 72.3 percent. The authors investigate possible predictors of retinopathy, including systolic blood pressure, duration of diabetes, and therapeutic regimen. They conclude that, because NIDDM is reaching epidemic proportions in Oklahoma Indians and most may experience retinopathy, frequent ophthalmological examinations are indicated for this high-risk population. 2 figures. 4 tables. 32 references. (AA-M).
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Longitudinal Studies of Incidence and Progression of Diabetic Retinopathy Assessed by Retinal Photography in Pima Indians Source: Diabetes Care. 26(2): 320-326. 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 incidence and progression of retinopathy (eye disease) using retinal photographs in Pima Indians and
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to compare the results with those obtained when retinopathy is assessed by direct ophthalmoscopy. The authors analyzed data from eye examinations of 411 people with diabetes who had at least two examinations between April 1982 and December 1990. Incidence and progression of retinopathy were evaluated by retinal photography and fundoscopy, and hazard rate ratios were calculated for various potential risk factors measured at baseline. Results showed that previously diagnosed retinopathy tended to progress, except in individuals with minimal nonproliferative retinopathy, among whom follow-up examinations were more likely to show not retinopathy. Diabetes duration, hyperglycemia (high blood glucose), the type of treatment for diabetes (insulin or oral hypoglycemic agents), and macroalbuminuria (protein in the urine) were associated with the development of retinopathy. Although fundoscopy detected fewer cases of retinopathy, risk ratios for most risk factors were similar when retinopathy was assessed by fundoscopy rather than retinal photography. The authors conclude that although retinopathy tends to worsen over time, some eyes show improvement, especially in patients with minimal nonproliferative retinopathy. As in other populations, glycemic control is the major modifiable risk factor for the development and progression of retinopathy. 3 figures. 3 tables. 24 references. •
Diabetic Retinopathy: Overlooked, Undertreated Source: Patient Care. 29(3): 12. February 15, 1995. Contact: Available from Medical Economics. 5 Paragon Drive, Montvale, NJ 07645. (201) 358-7200. Summary: This brief article reminds readers of the role of early detection of diabetic retinopathy in preventing visual impairment. The author stresses that many patients with diabetes are unaware of the advances that have been made in the treatment of retinopathy in recent years. As a result, many cases of mild, potentially treatable visual impairment are allowed to progress and become debilitating. Other topics include recent refinements in laser and vitreous surgery; the role of early screening and treatment; economic factors, including differences between the costs of screening versus treatment; and American Diabetes Association screening recommendations. The author also briefly mentions the role of improved glucose control in delaying the onset of retinopathy in patients with IDDM. 5 references. (AA-M).
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Telemedicine: Opportunities and Challenges for the Remote Care of Diabetic Retinopathy (editorial) Source: Archives of Ophthalmology. 117(12): 1639-1640. December 1999. Contact: Available from American Medical Association. Subscriber Services Center, P.O. Box 10945, Chicago, IL 60610. (800) AMA-2350 or (312) 670-7827. Fax (312) 464-5831. Email:
[email protected]. Summary: This editorial comments on the use of telemedicine in the remote care of diabetic retinopathy. Although several studies have evaluated the accuracy of photographs or digital images and their appropriateness for diagnosing and monitoring diabetic retinopathy, there has been no clear organizing framework or structure for how these images or attendant remote care systems should be evaluated or used. Before telemedicine can be used to provide routine eye care for diabetes or other conditions, various issues must be addressed. The most important concern is to determine the purpose of any telemedicine system. Next, from an evaluation standpoint, the system's performance must be sufficient compared with the appropriate criterion standard. For example, any study demonstrating the value of remote care in diabetic retinopathy
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needs to establish its validity and reliability relative to established criterion. Third, the technical validity of remote care images needs to be established from a technical perspective. Lastly, there is a need for studies analyzing the implementation of remote eye care of patients who have diabetes in the community clinical setting. Any efforts to substitute telemedicine on a continuing, regular basis for the routine eye care of patients who have diabetes or any other disease before addressing these issues is to potentially risk the health and vision of patients. 14 references. •
Epidemiology of Proliferative Diabetic Retinopathy Source: Diabetes Care. 15(12): 1875-1891. December 1992. Summary: This review article examines recent epidemiological data about the prevalence and incidence of and risk factors for proliferative diabetic retinopathy. In addition, the relation of proliferative retinopathy to other systemic complications associated with diabetes is reviewed. The data come mostly from the baseline and 4-year follow-up examinations of a large population-based study, the Wisconsin Epidemiologic Study of Diabetes Retinopathy (WESDR), which involved 996 younger-onset and 1370 older-onset people with diabetes. The authors conclude that their data suggest that hyperglycemia and, possibly, high blood pressure are related to proliferative retinopathy. They reiterate the importance of routine ophthalmological examinations to detect and treat proliferative retinopathy. 5 figures. 10 tables. 159 references. (AA-M).
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What You Need to Know About Diabetic Retinopathy Source: IM. Internal Medicine. 19(6): 18-26. June 1998. Contact: Available from Medical Economics. 5 Paragon Drive, Montvale, NJ 07645. (800) 432-4570. Summary: This review article provides primary care physicians with information on the nature of diabetic retinopathy and the preventive value of appropriate specialist referrals for patients with this condition. The article describes the course of diabetic retinopathy and discusses treatments tailored to the stage of the disease. Treatment of diabetic retinopathy usually involves laser photocoagulation, except in very advanced cases that require vitrectomy surgery. The article reviews evidence of the efficacy for these treatment methods. Various studies have demonstrated the benefit of photocoagulation treatment in eyes with high-risk proliferative retinopathy or clinically significant macular edema. Another study found an advantage of early vitrectomy surgery for people with type 1 diabetes with severe vitreous hemorrhage. The article offers guidelines for providing eye care for patients with diabetes and discusses the role of the primary care physician in instructing the patient in glycemic control. These physicians should teach and encourage tight glycemic control and keep in mind considerations concerning hypertension, hyperlipidemia, renal failure, cigarette smoking, pregnancy, and hypomagnesemia with regard to their patients with diabetes. In addition, the article lists and illustrates possible features of each stage of diabetic retinopathy and presents cases of diabetic retinopathy before and after treatment. 1 table. 28 references.
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Diabetic Retinopathy, Visual Acuity, and Medical Risk Indicators: A Continuous 10year Follow-up Study in Type 1 Diabetic Patients Under Routine Care Source: Journal of Diabetes and its Complications. 15(6): 287-294. November-December 2001.
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Diabetic Retinopathy
Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: This study describes the incidence and progression of diabetic retinopathy (diabetes associated eye disease) in relation to medical risk indicators as well as visual acuity outcome after a continuous follow up period of 10 years in patients with type 1 diabetes treated under routine care. The incidence and progression of retinopathy and their association to HbA1c (glycosylated hemoglobin, a measurement of blood glucose levels over time), blood pressure, urinary albumin (protein in the urine), serum creatinine levels (a measure of kidney function), and insulin dosage were studied prospectively in 452 patients with type 1 diabetes. In patients still alive at follow up (n = 344), 61 percent (69 patients) developed any retinopathy, 45 percent (51 patients) developed background retinopathy, and 16 percent (18 patients) developed sight threatening retinopathy. Progression from background to sight threatening retinopathy occurred in 56 percent (73 patients out of 131 patients). In 2 percent (6 patients of 335), visual acuity dropped to less than 0.5 and in less than 1 percent (3 patients of 340) to less than 0.1. Patients who developed any retinopathy and patients who progressed to sight threatening retinopathy had higher mean HbA1c levels over time compared to those who remained stable. Patients who developed any retinopathy had higher levels of mean diastolic blood pressure, whereas no differences were seen in systolic blood pressure levels between the groups. Analysis showed mean HbA1c to be an independent risk indicator for both development and progression of retinopathy, whereas mean diastolic blood pressure was only a risk indicator for the incidence of retinopathy. The authors stress that metabolic control is an important risk indicator for both development and progression of retinopathy, whereas diastolic blood pressure is important for the development of retinopathy in type 1 diabetes. However, overall the number of patients who became blind during 10 years of follow up was low. 3 figures. 3 tables. 40 references.
Federally Funded Research on Diabetic Retinopathy The U.S. Government supports a variety of research studies relating to diabetic retinopathy. 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 diabetic retinopathy. 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 diabetic retinopathy. The following is typical of the type of information found when searching the CRISP database for diabetic retinopathy:
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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Project Title: A NEW THERAPY FOR DIABETIC MACULAR EDEMA Principal Investigator & Institution: Ma, Jian-Xing; Laureate Professor; Medicine; University of Oklahoma Hlth Sciences Ctr Health Sciences Center Oklahoma City, Ok 73126 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): This is a R21/R33 phase-combined proposal aiming to develop a new treatment for diabetic macular edema using peptide angiogenic inhibitors. Vascular leakage is an early feature of diabetic retinopathy and can result in diabetic macular edema. Over-expression of VEGF is a major causative factor leading to vascular leakage in diabetic retinopathy. Currently, there is no satisfactory treatment for macular edema which remains a major cause of vision loss in diabetic patients. Plasminogen kringle 5 (K5) is a potent angiogenic inhibitor. Our recent studies have shown that K5 significantly decreases vascular leakage in the retina in the experimental diabetes, laser-induced choroid neovascularization and oxygen-induced retinopathy rat models. The K5- induced reduction of vascular leakage requires only less than one-tenth of the dose needed for the inhibition of neovascularization. Furthermore, our preliminary data suggest that the K5-induced reduction of vascular leakage may be through blocking hypoxia-induced VEGF over-expression in the retina, primarily in Muller cells. We hypothesize that a sustained ocular delivery of K5 may induce a longterm reduction of vascular leakage in diabetic retina and thus, may have therapeutic effect on cyctoid macular edema (CME) secondary to cataract surgery and diabetic macular edema. In the R21 phase, we propose to first reveal the mechanisms for the K5induced down-regulation of VEGF expression and identify the receptor or binding protein on the cell surface which mediates the K.5-induced reduction of permeability. As diabetic macular edema is a chronic complication of diabetes and requires a longterm treatment, we propose to develop a KS-polymer pellet to achieve a sustained release of K5. The ocular delivery routes of the K5 pellet will be optimized and the pharmacokinetics will be studied in rats. The long-term effect of the K5 pellet on vascular leakage will be determined in a diabetic rat model. The R21 phase will achieve the following goals: 1),to reveal the mechanism and identify the receptor mediating the K5 action, 2) to develop a sustained delivery system for K5 and 3) to prove the concept that a sustained delivery of K5 can induce a prolonged reduction of vascular leakage, The R21 phase will provide essential tools and information for starting the R33 phase. In the R33 phase, we will study the pharmacokinetics of K5 in ocular tissues and optimize the delivery route in normal dogs, With the optimized delivery route, the efficacy of K5 on reduction of vascular leakage will be confirmed in a dog model of vascular leakage induced by intravitreal injection of IGF-1. The possible toxicity of K5 to the retinal vasculature and retinal structure will be examined in both rats and dogs by histochemistry. The retinal function will be examined by ERG recoding. Although this project does not reach clinical trials, the proposed studies will obtain pre-clinical data such as pharmacokinetics, delivery route, efficacy and toxicity from more than one species, which are essential and useful for starting clinical trials. These studies will contribute to the development of a new treatment for CME and for diabetic macular edema. This new treatment will use natural human peptides and will be less invasive. This new therapy, if successful, can prevent vision loss from macular edema in diabetic patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Diabetic Retinopathy
Project Title: ALDOSE REDUCTASE AND DIABETIC EYE DISEASE Principal Investigator & Institution: Petrash, J Mark.; Professor; Ophthalmology and Visual Sci; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2002; Project Start 16-JUL-1988; Project End 31-MAR-2005 Summary: (Adapted from applicant's abstract): Diabetes mellitus is a major cause of blindness due to irreversible structural and functional changes to the lens and retinal vasculature. Mounting evidence from work with experimental animals suggests that aldose reductase, the first enzyme of the polyol pathway of glucose metabolism, plays a key role in the pathogenesis of diabetic eye disease. Inhibition of aldose reductase provides a therapeutically attractive means to delay the onset and/or progression of diabetic complications in the eye. However, effective drug therapy will depend on inhibitors with a high degree of binding specificity - a criterion not met by the currently available inhibitors. The aldo-keto reductase superfamily contains enzymes with structural and kinetic properties similar to aldose reductase. Many of these aldo-keto reductases are high affinity receptors for the same aldose reductase inhibitors previously evaluated but withdrawn from clinical trials. The long-range objective or our application is to identify structural features of aldose reductase and related enzymes that explain their functional differences and perhaps provide distinguishing features that can be exploited in drug design. A corollary goal is to establish the physiological role of aldose reductase, as long-term inhibitor therapy is likely to be required for effective prevention of diabetic eye disease. Three specific aims are proposed to address these goals: (1) We will characterize the functional properties and expression pattern in the normal and diabetic eye of a newly discovered human enzyme that appears to have functional properties strikingly similar to aldose reductase; (2) Using a combination of mutagenesis and x-ray crystallography, we will test the hypothesis that the C-terminal domain is a structural feature that distinguishes the function of aldose reductase from other closely-related enzymes; (3) We will test the hypothesis that the physiological role of aldose reductase has been conserved in the budding yeast S. cerevisiae and that strains containing deletions of yeast aldose reductase can be marker rescued by the human aldose reductase gene. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: INTERACTIONS
ANGIOSTATIN--MOLECULAR
MECHANISMS
AND
Principal Investigator & Institution: Sane, David C.; Associate Professor; Internal Medicine; Wake Forest University Health Sciences Winston-Salem, Nc 27157 Timing: Fiscal Year 2002; Project Start 30-SEP-1998; Project End 31-OCT-2003 Summary: (Adapted from Investigator's Abstract): Abnormalities in angiogenesis contribute to the pathogenesis of a variety of diseases including tumor growth and metastases, diabetic retinopathy, arthritis, psoriasis, and atherosclerosis. Angiostatin is a recently-discovered inhibitor of angiogenesis that has been shown to prevent the growth and metastasis of experimental tumors. The goal of this proposal is to understand the molecular mechanisms by which angiostatin inhibits cellular growth and migration. Based on its striking homology with hepatocyte growth factor (HGF), a known inducer of angiogenesis, it is hypothesized that angiostatin may act as a competitive inhibitor of HGF, perhaps by binding, but not activating the c-met receptor. This hypothesis will be tested in cell proliferation and migration assays and with competitive cellular binding studies. Another potential mechanism of action of angiostatin involves its ability to displace plasminogen and thereby inhibit plasmin-
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mediated pericellular proteolytic activities, including the activation of procollagenases and the conversion of latent TGF-B to the active form. A final mechanism that to be examined is the potential ability of angiostatin to inhibit vitronectin-mediated haptotaxis, by disrupting urokinase receptor (UPAR) or integrin-mediated adherence of cells to this extracellular matrix protein. Recombinant vitronectin (wild and mutant forms) will be used to evaluate angiostatin's effect on VN-supported haptotaxis. Preliminary studies demonstrate that HGF (like angiostatin) binds to vitronectin. Domain deletion mutants of VN will be used to determine the VN binding site of HGF. The ability of angiostatin and HGF to compete for the same binding site on VN will also be examined using ELISA-based assays. By virtue of its ability to mediate haptotaxis and also approximate either pro or anti-angiogenic factors close to the cell, VN may modulate angiogenesis. These studies will lead to a better understanding of the mechanisms of angiogenesis inhibition by angiostatin. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ANTI-ANGIOGENIC SIGNALING MOLECULES IN RETINAL CELLS Principal Investigator & Institution: Rahimi, Nader; Ophthalmology; Boston University Medical Campus 715 Albany St, 560 Boston, Ma 02118 Timing: Fiscal Year 2002; Project Start 01-FEB-2002; Project End 31-JAN-2005 Summary: Angiogenesis, formation of new blood vessels from pre-existing vessels is a hallmark of many eye diseases such as age-related macular degeneration, proliferative diabetic retinopathy, retinopathy of prematurity and vascular glaucoma, which are among leading cause of visual loss in the USA and throughout the world. Vascular endothelial growth factor (VEGF), the major stimulator of angiogenesis, elicits its effect by binding to and activating two endothelial receptors namely VEGFR-1/FLK-1 and VEGFR-2/FLT-1. Although activation of VEGFR-2 has been demonstrated to be an essential requirement for induction of angiogenesis, the role of VEGFR-1 in angiogenesis is largely unknown. We will investigate the molecular mechanisms responsible for action of VEGFR-1, such as activation of signaling molecules or induction of immediate early genes (IEG) that might drive its anti-angiogenesis effects in endothelial cells. The significance of the results obtained from the proposed study lies in their potential to provide fundamental information on how VEGFR-1 communicates to control/restrain angiogenesis in endothelial cells. The importance of angiogenesis in ocular diseases is well recognized. our long-term goal is to begin to apply the information obtained from this project to the design of strategies to regulate angiogenesis in clinical settings. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CELL COMMUNICATION IN THE VERTEBRATE RETINA Principal Investigator & Institution: Miller, Robert F.; Professor; Neuroscience; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2002; Project Start 30-SEP-1978; Project End 31-MAR-2004 Summary: (Verbatim from applicant's abstract): This research application represents a broad investigation into the mechanisms of cell communication in the vertebrate retina. Our objectives are centered on three main issues. These include (1) the mechanisms in the inner retina which are subserved by the release of glutamate and the different types of glutamate receptors, both ionotropic and metabotropic, which interact to regulate the excitability of ganglion cells; (2) the identification and biophysical characterization of voltage-gated Ca2+ channels in ganglion cells with special emphasis on T-type Ca2+ channels, their pharmacological properties and cellular distribution in the dendrites and
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Diabetic Retinopathy
soma. We plan to evaluate how T-type Ca2+ channels contribute to nerve impulse generation and whether these ion channels play a role in amplifying synaptic currents which are generated on the dendrites. The third broad mission of this application is dedicated to a better understanding of dendritic physiology by recording from dendrites and isolated dendrosomes to further define the physiological properties of AMPA, NMDA and KA receptors. The methods used in this study will include electrophysiology, Ca2+ imaging and the use of photolysis to introduce chemical agents quickly and apply them locally at visually targeted dendritic regions. These experiments will be carried out in the amphibian retina and are designed to enhance our understanding about the mechanisms by which cells interact with one another and contribute to the excitability of retinal ganglion cells. The health-related implications of this research are extensive and relate to the mechanisms which control cellular functions of ganglion cells and how these mechanisms may help or hinder the stability of these cells when confronted with the stress of several different disease states, including glaucoma and diabetic retinopathy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: COHORT REGISTRY OF TYPE 1 DIABETES Principal Investigator & Institution: D'alessio, Donn J.; Preventive Medicine; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2001; Project Start 01-MAY-1987; Project End 31-AUG-2005 Summary: (Adapted from Investigator's Abstract) The decade between 1987 and 1997, spanning the Diabetes Control and Complications Trial (DCCT) and other clinical trials, saw confirmation of the importance of intensive therapy to control glycemic levels in Type 1 diabetes. Accompanying this advance in diabetes treatment, molecular studies emerged and provided clues to possible pathways for long term vascular complications perhaps most notably in the area of advanced glycation end products. The investigators' point out that their geographically based cohort presents an excellent opportunity to examine how these recent advances in clinical diabetes and basic science apply to prevention of complications in the community. Detailed information from this cohort followed from diabetes diagnosis during 1987-1992 includes a valuable longitudinal plasma bank. The cohort provides a unique baseline to compare diabetes management, glycemic control and outcomes in the post-DCCT era. As the investigators enrolled incident cases, they have information from diagnosis on children and adolescents. They propose to expand their existing data base, to use their existing resources including the plasma bank, and to incorporate promising new pathogenic testing by: (a) recruiting over 5 years a new post-DCCT cohort, (b) completing a 9 year follow-up for microvascular outcomes on the existing cohort, and performing antibody studies for methylglyoxal modified protein (an advanced glycation end product, or AGE) and sex hormone testing on our stored plasma. These proposed activities will allow the investigators to pursue the following specific aims: (1) compare trends in diabetes management and outcomes for individuals diagnosed before and after the announcements and dissemination of the DCCT results; (2) firmly establish retinopathy incidence and change in urinary albumin excretion rates through the first 9 years of Type 1 diabetes and their relationship to early risk factors; and (3) validate the role of a new plasma marker for intracellular AGE in glycemic control, retinopathy and change in urinary albumin excretion rates. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: COLOR DOPPLER IMAGING OF THE RETINA AND CHOROID Principal Investigator & Institution: Glucksberg, Matthew R.; Professor and Chairman; Biomedical Engineering; Northwestern University 633 Clark Street Evanston, Il 60208 Timing: Fiscal Year 2002; Project Start 01-JUN-2000; Project End 31-MAY-2004 Summary: Defects in the regulation of retinal and choroidal flow are part of the etiology of diabetic retinopathy, glaucoma, and other vision-threatening disorders, yet the physics and physiology controlling of blood flow to the retina is poorly understood, at least in part because of the limitations of current methods of measuring blood flow. The goal of this research is to quantitatively study the control of flow and the hemodynamics in the choroidal and retinal circulations and their relationships to retinal disease. The hypothesis is that blood flow in the retinal and choroidal circulations is not homogeneous and that increased heterogeneity in blood flow may be an early indicator of dysfunction of the retinal and choroidal circulations. As part of this work simultaneous, continuous and quantitative measurements of tissue perfusion in the choroidal and retinal circulations will be made to allow study of how the retina and choroidal circulations interact in response to physiological conditions. Previous investigations of the role of the vasculature in health and disease have been hampered by the limits of technology. In this project Color Doppler Optical Coherence Tomography (CDOCT), a novel non-invasive imaging technology, will be adapted to measure hemodynamic parameters in the circulations that serve the retina. The specific aims will first address the instrumentation and quantification of blood flow and then validate the results using in-vivo comparison to Laser Doppler Flowmetery, the most commonly used current method of assessing perfusion. The method will then be used in animal experiments to determine the effects of perfusion pressure and blood gasses on the regional distribution of blood flow and local hematocrit in the retinal and choroidal circulations, with and without ganglionic blockade and other maneuvers which act differently on the two circulations. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DIABETES AND INCONTINENCE Principal Investigator & Institution: Brown, Jeanette S.; Professor and Director; Obstetrics, Gynecology & Reproductive Scis; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2006 Summary: Jeanette S. Brown, M.D. is Professor of Obstetrics Gynecology and of Epidemiology & Biostatistics at the University of California, San Francisco (UCSF). She is Co-Director of the newly established UCSF Women?s Health Clinical Research Center and Director of the UCSF Women?s Urologic Research Group. Dr. Brown also developed and now is Director of UCSF Women?s Health Research Center Fellowship in Clinical Research and Associate Director of the UCSF/ San Francisco VAMC (SFVAMC) Women?s Health Clinical Research Fellowship. Additionally, Dr. Brown is Director of the UCSF Women?s Continence Center. Formal training in clinical research methods and support from a 4-year Mentored Clinical Scientist Award provided the experience and skills to become an independent investigator and build a multidisciplinary research team in patient-oriented research. The proposed research is designed to determine among women with diabetes: prevalence and incidence of urinary incontinence by type (urge, stress, and mixed) and severity, both overall and by race; risk factors associated with incontinence, especially aspects of diabetes severity (duration, treatment, glycemic control, presence of microvascular complications
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Diabetic Retinopathy
including retinopathy, nephropathy and neuropathy) that are associated with greater risk or severity of urinary incontinence; and whether interventions including glycemic control or weight reduction prevent or reduce severity of urinary incontinence among women with diabetes. Questionnaires, laboratory, and outcome data from a triad of diabetes studies including women with impaired glucose tolerance, type 2 and type 1 diabetes and 2 population-based cohort studies that include women with and without diabetes will be analyzed. Dr. Brown has the enthusiastic support of her department UCSF investigators and other internationally recognized clinical researchers to pursue her research goals. She is a senior mentor to young clinical investigators and will develop a unique joint Urogynecology and Urology 3-year clinical research fellowship. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DIABETIC MACULAR EDEMA CLINICAL RESEARCH NETWORK Principal Investigator & Institution: Beck, Roy W.; Director; Jaeb Center for Health Research, Inc. Suite 350 Tampa, Fl 33647 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-JAN-2009 Summary: (provided by applicant): This application is submitted in response to the RFA for a Coordinating Center (CC) to serve the needs of the Diabetic Macular Edema Clinical Research Network. The network is expected to include 25 clinics, a Fundus Photograph Reading Center (FPRC), Study Chairman's Office, and a CC. The main objective of this network is to evaluate promising new treatment approaches for diabetic macular edema (DME). The role of the CC is critical for the success of a multi-center study. The importance to the network of having an experienced CC, particularly one with experience in eye disease trials, is sufficiently self-evident in the RFA that it needs no justification statements here. While the core principles followed by a CC in study protocol design, quality control, study conduct, and statistical analyses have changed little in the last 20 years, through technologic advances the approach to carrying out many CC functions has changed considerably. Advances in computing and in access to the Internet have provided new opportunities for a CC to enhance quality control measures and at the same time increase efficiency. This evolution in CC trial management will continue as technology continues to advance. For essentially all aspects of the project, we will draw upon our experience in our past and current studies. We have coordinated numerous multi-center eye disease investigator groups and have experience with all of the CC functions and responsibilities that will be part of this project. We have considerable experience with study groups conducting multiple, concurrent and consecutive protocols, a likely aspect of this project. We have been innovative in our 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 we have worked to develop a data management system that is as generic as possible so a new study can be readily added to an existing data management structure. This extends to website development in which the web-based applications we have developed for our prior and current studies will serve as a template for this project. This proposal will detail the capabilities of the Jaeb Center to serve as the CC for the network and our plans to carry out the objectives of the project. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DIABETIC MACULAR EDEMA CLINICAL RESEARCH NETWORK FUND* Principal Investigator & Institution: Davis, Matthew D.; Professor; Ophthalmology and Visual Sci; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-JAN-2009 Summary: (provided by applicant): The University of Wisconsin Fundus Photograph Reading Center (UW FPRC) proposes to serve as photograph reading center for the DME Clinical Research Network. To accomplish this, we propose to: (I) Collaborate with other network investigators to develop ideas for clinical trials of promising new DME treatments, construct study protocols, carry out approved studies, analyze the resultant data, and prepare manuscripts. (2) Adapt or develop procedures for documenting and grading DME. We can provide protocols for DME imaging (color stereoscopic fundus photographs, fluorescein angiograms, and optical coherence tomograms), and are experienced at orienting, certifying, and giving feedback to clinic photographers. By extending the Early Treatment Diabetic Retinopathy Study classification, we have protocols for evaluation/grading of DME from color photographs and angiograms. We are developing a protocol for assessment of OCT scans. We are prepared to modify these protocols further, if necessary, to define the eligibility and outcome criteria appropriate to network goals. The UW FPRC principal investigator and staff are experienced at participation in collaborative multi-center clinical trials (e.g., Diabetic Retinopathy Study, Early Treatment of Diabetic Retinopathy Study, Diabetes Control and Complications Trial, and several drug trials) and in networks to conduct them (e.g., the Study of the Ocular Complications of AIDS), and are strongly committed to the study of DME and its potential treatments as a major public health priority. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DIABETIC RETINOPATHY: AR1 AS A NOVEL THERAPEUTIC TARGET Principal Investigator & Institution: Smith, Sylvia B.; Professor; Cellular Biology and Anatomy; Medical College of Georgia 1120 15Th St Augusta, Ga 30912 Timing: Fiscal Year 2004; Project Start 01-JAN-2004; Project End 31-DEC-2007 Summary: (provided by applicant): The goal of this project is to determine the pathogenesis of and neuroprotection against retinal ganglion cell (RGC) death in diabetic retinopathy. Many RGCs die within the first 2 years of disease onset. The RGC death is thought to be due to overstimulation of the N-methyl-D-aspartate (NMDA) receptor that leads to excessive levels of intracellular calcium, which triggers the cell death cascade. Glutamate, which is elevated in the vitreous body and retina of diabetic patients, is the primary excitotoxin that activates the NMDA receptor. Homocysteine, which accumulates in the plasma of diabetic patients, induces RGC death when injected intravitreally. NMDA receptor activation requires co-activation of its glycine binding site and D-serine is the endogenous physiologic ligand for this site. Serine racemase is the enzyme responsible for the endogenous generation of D-serine. One of the goals of the project is to elucidate the molecular events involved in the extracellular accumulation of the MDA receptor agonists, glutamate and homocysteine, and the coagonist D-serine. D-serine and serine racemase are expressed in retina, but their involvement in diabetes has not been investigated. AIM 1 will test the hypothesis that diabetes is associated with increased levels of D-serine and serine racemase leading to enhanced activation of the NMDA receptor by glutamate and homocysteine. AIM 2 will test the hypothesis that diabetes is associated with altered function of transport systems
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for glutamate (EAATs, x[c-]), homocysteine and D-serine (ATB0,+) and that their altered function may provide the molecular basis for the diabetes-associated increase in extracellular levels of glutamate, homocysteine and D-serine. Therapeutic intervention strategies targeted at blocking NMDA receptor stimulation could prevent RGC death and may delay other manifestations of diabetic retinopathy. Type 1 sigma receptor (sigmaR1) is a nonopiate, nonphencyclidine binding site that demonstrates robust neuroprotective properties including inhibition of ischemia-induced glutamate release and depressed neuronal responsivity to NMDA receptor stimulation. SigmaR1 is expressed abundantly in RGCs and continues to be expressed under hyperglycemic conditions. Agonists specific for sigmaR1 may have potential as therapeutic agents in providing neuroprotection in the early stages of diabetic retinopathy. Our preliminary data show that (+)-pentazocine, a sigmaR1 agonist, prevents RGC death in vitro induced by glutamate and homocysteine and in vivo induced by diabetes. AIM 3 will test the hypothesis that sigmaR1 agonists will be protective against RGC death characteristic of diabetic retinopathy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DYSLIPIDEMIA DYSFUNCTION
AND
RETINAL
ENDOTHELIAL
CELL
Principal Investigator & Institution: Busik, Julia V.; Physiology; Michigan State University 301 Administration Bldg East Lansing, Mi 48824 Timing: Fiscal Year 2003; Project Start 15-JUN-2003; Project End 31-MAY-2005 Summary: (provided by applicant): Diabetic retinopathy represents the leading cause of blindness in adults. Diabetic retinopathy is a disease of the retinal microvessels characterized by capillary occlusions, microaneurysms, selective loss of pericytes, acellular capillaries, hypertrophy of the basement membrane, angiogenesis and neovascularization. While the initial determinants of retinal microvascular damage are not well understood, recent studies suggest that diabetic retinopathy is a low-grade chronic inflammatory disease. As such, recent studies document increased leukocyte attachment and transmigration into the vascular intima. The increased adherence of leukocytes to endothelial cells likely involves induction of specific adhesion molecules, such as ICAM-1. The factors elevating cellular adhesion molecules are not well defined, but likely involve hyperglycemia and dyslipidemia associated with diabetes mellitus. Our preliminary studies show that treating human retinal vascular endothelial (hRVE) cells with specific fatty acids leads to the induction of ICAM-1, as well as alterations in several signaling pathways. We hypothesize that exposure of hRVE cells to specific fatty acids leads to the formation of specific bioactive lipids that cause alterations in cell signaling and gene expression and lead to increased expression of adhesion molecules and leukocyte attachment. To test this hypothesis, the following aims are proposed: 1) To evaluate the effects of fatty acids and glucose on adhesion molecule expression and cell signaling in hRVE cells. 2) To correlate changes in adhesion molecule expression and cell signaling to the production of specific bioactive lipids. The outcome of this work will lead to a better understanding of how diabetic dyslipidemia contributes to altered hRVE cell phenotype and the onset and progression of diabetic retinopathy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EFFECT OF ISOPROSTANES ON RETINAL TRANSMITTER RELEASE Principal Investigator & Institution: Opere, Catherine A.; Pharmacy Sciences; Creighton University 2500 California Plaza Omaha, Ne 68178
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Timing: Fiscal Year 2003; Project Start 15-APR-2003; Project End 31-MAR-2005 Summary: (provided by applicant): Isoprostanes (IsoP's) are a series of prostaglandinlike compounds that are formed in abundance in vivo by a non-enzymatic, free radical catalyzed peroxidation of arachidonic acid independent of cyclooxygenase. In addition to providing a reliable measure of in vivo and in vitro oxidative stress, IsoP's can exert pharmacological effects in some tissues. A review of literature revealed that very few studies have addressed the effects of IsoP's on neurotransmitter release from central or peripheral tissues. Although IsoP's have been reported to modulate sympathetic neurotransmission from anterior uveal tissues, no studies have investigated the potential regulatory effects of these compounds on neurotransmission in the retina. In the present study, we will test the hypothesis that IsoP's can modulate glutamate, gamma-aminobutyric acid (GABA) and dopaminergic transmission in the retina both in vitro and in vivo. The overall objective of the present study is to examine the effect of different series of IsoP's (A1, E1, E2, F1, F2 and F3) on glutamate, GABA and dopamine release from retinae both in vitro and in vivo. Experiments in this project have, therefore, been designed to answer the following questions: (i) do different IsoP's alter the release and/or availability of glutamate, GABA and dopamine in vitro and in vivo? (ii) are the effects produced by IsoP's comparable to those of other arachidonic acid metabolites (prostaglandins and thromboxanes)? (iii) what is the role of presynaptic IsoP heteroreceptors in the effects caused by these compounds on glutamate, GABA and dopamine in vitro and in vivo? We anticipate that the results of the present study will improve our understanding of the basic mechanisms involved in the effects of IsoP's on retinal glutaminergic, GABAergic and dopaminergic transmission. Furthermore, these studies may reveal pharmacologically/toxicologically accessible sites for the action of IsoP's in the retina. We hope that observations made in this project will be applicable to diseases of the retina associated with the generation of free radicals and oxidative damage such as ischemia, glaucoma, diabetic retinopathy and age-related macular degeneration. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EPIDEMIOLOGY OF AGE-RELATED OCULAR DISEASE Principal Investigator & Institution: Klein, Ronald; Professor; Ophthalmology and Visual Sci; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2002; Project Start 16-JUN-1987; Project End 31-MAY-2007 Summary: (Applicant's Abstract) This proposal describes the follow-up of a populationbased cohort study aimed at determining the long-term (15-year) impairments of aging. In addition we will determine the incidence and associated risk factors for other agerelated ocular conditions such as branch retinal vein occlusion, retinal arteriolar ernboli, and epiretinal membranes. We will examine age-related hyperopic shift in refraction. The population was 43-86 years of age at the census prior to the first survey in 1987-88. Standardized protocols for interviews, examinations, ocular photography, and grading have been employed during the baseline (n--4,926), the 5-year (n7-3,816) and 10-year (n7-2764) examinations. Refusal rates have been low. Because this cohort initially included a substantial number of middle-aged adults, the study provides a unique opportunity to follow the course of these eye conditions and document their natural history as this population enters the age of marked increase in disease incidence. The study in its initial prevalence survey and at the 5 and I 0-year follow-ups obtained information about cardiovascular disease, hypertension, diabetes and other medical conditions, cigarette smoking, nutritional supplements, light exposure, drug use history, and blood factors (e.g. glycosylated hemoglobin, total and HDL cholesterol). The 15-year
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Diabetic Retinopathy
follow-up is essential because the cohort is maturing and the number of cases of disease will be great enough to test many of the hypotheses that could not be precisely tested when the population was younger. In addition, at the 5-year examination, additional questions were added regarding subjective assessment of visual ability and history of falls and fractures, while continuing to monitor other risk factors and ocular variables that were measured at baseline. We will examine the relationship of impaired vision from specific age related eye conditions to self-reported visual function, falls, and fractures and nursing home placement. Findings regarding age-related maculopathy, cataract other retinal diseases will be of great public health importance in helping to predict the requirement for visual care and rehabilitative services as the population ages, and in directing further efforts at preventing these conditions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EVALUATING INTERVENTIONS
ALTERNATE
RETINOPATHY
SCREENING
Principal Investigator & Institution: Walker, Elizabeth A.; Associate Professor; Epidemiology & Population Health; Yeshiva University 500 W 185Th St New York, Ny 10033 Timing: Fiscal Year 2002; Project Start 07-SEP-2000; Project End 31-AUG-2005 Summary: Diabetic retinopathy is serious, costly and prevalent, especially among minority populations. Annual ophthalmic examinations and appropriate follow-up care would result in substantial savings in preventable vision loss, health care costs, and lost productivity. However, most people do not receive these services. In our previous study, we doubled the rate of ophthalmic examinations in a low-income AfricanAmerican population using a multi-component intervention. We now propose to evaluate the incremental effects and costs of components of that intervention in a broader diabetes population, including Spanish-speaking patients The specific aims of the proposed study are to: 1) test the hypothesis that a tailored telephone intervention will result in a higher rate of ophthalmic examinations than a standard print intervention; 2) improve understanding about reasons why people obtain an ophthalmic examination and assess differences in subgroups (gender and Spanish language preference); 3) improve understanding about reasons why people who are diagnosed with diabetic eye disease do or do not receive recommended follow-up treatment; and 4) conduct cost-effectiveness analyses. The study design is a randomized, controlled intervention trial with masking; the individual is the unit of sampling, assignment, and analyses. A total of 800 patients with type 1 or type 2 diabetes mellitus who have not had a dilated eye examination in the last year will be sampled from the databases of two large urban health systems. After eligibility is ascertained and written informed consent is obtained, patients will be randomized within site by gender and preferred language (Spanish or English) to either the tailored telephone group or the standard print group. Sample size determinations are based on having sufficient power to detect differences between groups at the p<0.05 level of significance. The main study outcome will be receipt of a dilated eye exam at 6 months post-randomization as ascertained by medical record abstraction, with a second outcome assessment conducted at 18 months post randomization. Receipt of follow-up care for diagnosed eye disease will also be assessed. Pre- and post-intervention telephone interviews will provide data on changes in knowledge, beliefs, risk perceptions and behavior regarding ophthalmic exams. Cost data will be collected using standardized methods. Study results will inform implementation and dissemination of practical, low-cost interventions to increase
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ophthalmic examinations and follow-up care, and thereby contribute to a decrease in vision loss and health care costs in diabetes populations. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EXPRESSION AND REGULATION OF RETINAL ANGIOTENSIN II Principal Investigator & Institution: Senanayake, Preenie E.; Cleveland Clinic Foundation 9500 Euclid Ave Cleveland, Oh 44195 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2006 Summary: (provided by applicant): The long-term goal of my research is to understand the role of hypertension in the pathogenesis of diabetic retinopathy. In humans and other species with vascularized retinas, the rates of glucose and oxygen utilization by the retina are 3-fold higher than in any other tissue. The retinal circulation is highly sensitive to local tissue metabolic needs and susceptible to damage from circulatory dysfunction. In diabetic patients, capillary non-perfusion has been shown to precede neovascularization. Capillary ischemia could be due at least in part to obstruction caused by abnormal or accelerated growth of vascular smooth muscle cells. The increases in angiotensin (Ang) II and insulin levels that occur in hypertension and noninsulin dependent diabetes (type 2) may contribute to this process within the small ophthalmic arteries. Thus, insulin and Ang II could act in a synergistic manner. Inhibiting the renin-angiotensin system (RAS) confers a therapeutic benefit in the treatment of diabetic retinopathy. Although the pathogenesis of diabetic retinal complications is not fully understood, emerging evidence implicates the RAS, with its mitogenic and trophic actions and its influence on angiogenesis. Ang II may be produced locally in the retina, and could play a role in the development and/or maintenance of proliferative diabetic retinopathy. Our hypothesis is that the retina is a target tissue for Ang II in rats with hypertension and/or diabetes. We will test this hypothesis in the stroke-prone spontaneously hypertensive rat (SHRSP) with streptozocin-induced diabetes, now shown to develop signs of diabetic retinopathy that are reversed by an Ang receptor antagonist. Specific aims are: 1) To determine the tissue-specific expression of Ang receptor subtype transcripts and proteins, 2) To examine tissue-specific expression of angiotensinogen, renin, angiotensin converting enzyme and Ang II in the retina. Molecular, biochemical and immunohistochemical approaches will be combined. 3) To assess the mechanism of regulation of Ang II in the retina under physiological and genetic perturbations of the RAS. Electroretinography will be used to evaluate retinal function, which will be correlated with blood pressure measured by tail cuff. These studies will not only expand our understanding of the function of the RAS in a novel tissue, but may also have important therapeutic implications. Ultimately retinal Ang receptors could be specifically targeted with selective therapeutic agents to prevent the development of proliferative diabetic retinopathy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: FEMTOSECOND LASER VITREOUS PHOTODISRUPTION Principal Investigator & Institution: Mcdonnell, Peter J.; Director; Ophthalmology; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2006 Summary: (provided by applicant): The National Eye Institute has reported that Diabetic Retinopathy is a major cause of blindness. Due to the prevalence of this disease, NEI's program objective for the next 5 years includes the development of better
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Diabetic Retinopathy
methods of prevention and therapy of diabetic retinopathy. It is this project's long term objective to develop a non-invasive, trans-pupillary photodisruption laser system to perform safe and effective vitreolysis for the prevention and treatment of diabetic retinopathy. The specific objectives include: 1. Develop and optimize a trans-pupillary femtosecond laser delivery system to perform vitreolysis in rabbit eyes. 2. Measure development, growth and complications in rabbit eyes after core vitreolysis and lysis of cortical vitreous adjacent to the retina. 3. Determine the efficacy of laser vitreolysisinduced PVD in inhibiting hemorrhage and tractional retinal detachment in a VEGFBFGF growth factor-induced model of vitreoretinal angiogenesis. The laser delivery system and laser parameter optimization will be tested on animal cadaver eyes. Paired sample live-animal experiments will be performed to assess the safety and efficacy of the developed procedure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENE NEOVASCULARIZATION
EXPRESSION
CHANGES
IN
RETINAL
Principal Investigator & Institution: Duh, Elia J.; Professor; Ophthalmology; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 01-AUG-1999; Project End 31-JUL-2004 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENE THERAPY FOR RETINAL DETACHMENT Principal Investigator & Institution: Tomasek, James J.; Professor & Vice Chair for Research; Cell Biology; University of Oklahoma Hlth Sciences Ctr Health Sciences Center Oklahoma City, Ok 73126 Timing: Fiscal Year 2003; Project Start 16-JAN-2003; Project End 31-DEC-2005 Summary: (provided by applicant): Retinal detachment with subsequent loss of vision is a major clinical problem associated with a number of ocular diseases, including proliferative vitreoretinopathy (PVR) and proliferative diabetic retinopathy (PDR). Surgery, the only treatment currently available, has a high rate of recurrence of fibrous epiretinal membrane formation and retinal detachment. Smooth muscle (SM) alphaactin containing myofibroblasts are a major cell type present in the epiretinal membranes that form in PVR and PDR and it is these cells that are responsible for generation of force leading to retinal detachment. The long-term goal of this research is to develop a gene therapy-based approach that targets and blocks the contraction of the myofibroblast. The first objective of this project is to develop a myofibroblast-specific promoter. Recent studies have suggested that the regulation of SM alpha-actin expression is different in myofibroblasts and smooth muscle cells and these studies have begun to identify regulatory elements in the promoter bf SM alpha-actin that might be responsible for these differences. Therefore, the first specific aim is to identify regulatory elements within the SM alpha-actin promoter that are specific to myofibroblasts in epiretinal membranes. To address this aim we will use transgenic mice containing a SM alpha-actin promoter/LacZ transgene in which specific regulatory elements have been deleted or mutated. These mice will be mated with a transgenic mouse model in which an epiretinal membrane containing myofibroblasts forms and contracts, with subsequent retinal detachment. The second part of our long-term goal is to be able to block the contraction of myofibroblasts in the epiretinal membranes. The expression of SM alpha-actin in myofibroblasts is functionally related to the ability of these cells to
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generate large amounts of contractile force. Therefore, the second specific aim is to determine whether knocking out the SM alpha-actin gene will decrease or inhibit retinal detachment. Specifically we will determine the length of time it takes for retinal detachment to occur in control and SM alpha-actin-null mice. These studies will provide the basis for developing a gene therapy-based approach that can specifically target myofibroblasts in epiretinal membranes and block their generation of contractile force thereby blocking epiretinal membrane contraction and retinal detachment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENETIC CONTROL OF VASCULAR REMODELING Principal Investigator & Institution: Dumont, Daniel J.; Associate Professor; Sunnybrook & Women's Coll Hlth Scis Ctr S132 Toronto, on M4n 3M5 Timing: Fiscal Year 2002; Project Start 14-AUG-2001; Project End 31-JUL-2005 Summary: Angiogenesis, the growth of blood vessels from pre- existing vessels, which is known to play a pivotal role in the progression of several different diseases, including diabetic retinopathy, arteriosclerosis and cancer. To-date, virtually all genes that have been shown to play a role in early vascular development of the embryo, are also expressed in the endothelium of these diseased tissues. Thus, implies that the disregulation of gene expression in the endothelium in these diseased tissues recapitulates the genes expressed in the activated endothelium of the developing embryo. The genetic control of this vessel growth is currently poorly understood, however several studies using gene-targeting in mice have revealed that numerous diverse signaling pathways produce overlapping defects in vascular remodeling. The working hypothesis for this proposal is that the defects observed in these different mouse mutants are the consequence of misregulation of a common subset of genes whose expression control vascular remodeling. This research will use gene expression profiling by gene chip and SAGE analysis to examine the genes expressed in four different mouse mutants that affect very different signaling pathways and result in overlapping vascular remodeling defects. The differential expression of genes in the heart and yolk sacs of the Tek/Tie2, Endoglin, VEGFR3, and Notch1 mouse mutants will be compared. This work will provide considerable insight into the role of these disparate signaling modalities in the angiogenic response. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GENETICS OF DIABETIC RETINOPATHY Principal Investigator & Institution: Hanis, Craig L.; Professor; Human Genetics Center; University of Texas Hlth Sci Ctr Houston Box 20036 Houston, Tx 77225 Timing: Fiscal Year 2002; Project Start 01-JAN-1999; Project End 31-DEC-2003 Summary: (Applicant's Abstract) Diabetic retinopathy substantially contributes to the morbidity of type 2 diabetes mellitus and is a strong predictor of subsequent, often early, mortality in those with diabetes. Susceptibility to type 2 diabetes has long been known to have a substantial genetic component. Not only does diabetes aggregate in families, but so do its complications. Preliminary results demonstrate an 8.3 fold increased risk for retinopathy in diabetic siblings of a diabetic with no retinopathy. It is likely that diabetes susceptibility alleles impact the clinical courses of the disease and development of retinopathy. It is also plausible that other genes influence susceptibility to retinopathy, but exert their influence only after the development of diabetes. To determine the contribution of genetic factors to diabetic retinopathy, 1,000 Mexican Americans with type 2 diabetes distributed in 750 sibling pairs will undergo detailed
26
Diabetic Retinopathy
eye examinations on 2 occasions (2.5 years apart). Examinations will include stereoscopic fundus photography and scoring according to standard protocols. Except for the retinal examinations, these individuals have been and are being characterized in ongoing studies in Starr County, Texas. These characterization includes genotypes at markers spanning the entire genome at an average distance of 8 to 10 centi-Morgans. All marker data will be available prior to the completion of the first round of retinal examinations. Documentation of the presence and severity of diabetic retinopathy in this sibling pair genotype resource and an additional confirmatory set of 200 individuals with diabetes will permit: 1) Determining the sibling pair concordance for retinopathy, 2) Localizing retinopathy susceptibility loci based on two-point and multi- point sibling pair linkage analysis, and 3) Identification of variation by DNA sequence scanning of genes in linked regions impacting on the presence and development of retinopathy. The end result will be improved understanding of mechanisms and exploitable pathways for moving retinopathy treatment from palliative to preventive. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GLIAL-NEURONAL INTERACTIONS IN THE RETINA Principal Investigator & Institution: Newman, Eric A.; Professor; Neuroscience; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2002; Project Start 01-JUL-1990; Project End 31-MAR-2005 Summary: (Verbatim from applicant's abstract): The long-term objective of this project is to determine the functions of glial cells (Muller cells and astrocytes) in the mammalian retina. It is widely recognized that glial cells have important support functions in the retina, including uptake of neurotransmitters and regulation of extracellular potassium and pH. The role of glial cells in direct modulation of neuronal activity is not yet understood, however. In the preceding project period, we demonstrated that intercellular Ca2+ waves can be propagated through glial cells in the rat retina and that these glial Ca2+ waves modulate spike activity in neighboring neurons. In the proposed project period, we will extend our studies of glial modulation of neuronal activity and explore additional aspects of glial Ca2+ signaling with the goal of determining the significance of these interactions in vivo. The specific aims for the project period are: (1) to identify natural stimuli that elicit Ca2+ signals in retinal glial cells; the hypotheses to be tested are that: (a) chemicals released under normal or pathological conditions evoke glial Ca2+ increases, and (b) light stimulation evokes glial Ca2+ increases; (2) to test the hypothesis that spontaneous Ca2+ oscillations in glial cells modulate the activity of neighboring neurons, using regression analysis to correlate neuronal spike activity and membrane potential with Ca2+ levels in adjacent glial cells displaying spontaneous Ca2+ oscillations; (3) to characterize mechanisms of glial cell modulation of neuronal activity; the hypotheses to be tested are that: (a) excitatory neuronal modulation is mediated by release of glutamate from glial cells onto neurons, and (b) inhibitory modulation is mediated indirectly by glial activation of inhibitory amacrine cells; (4) to elucidate the mechanism by which Ca2+ waves are propagated in retinal glial cells; the hypothesis to be tested is that wave propagation is mediated by the release of ATP, which functions as an extracellular messenger; and (5) to characterize physiological changes in retinal glial cells elicited by propagation of Ca2+ waves; the hypotheses to be tested are that: (a) Ca2+ increases modulate inward rectifier potassium and Ca2+dependent potassium conductances, and (b) Ca2+ increases generate intracellular pH variations in retinal glial cells. Glial cells have been implicated in many types of retinal pathology, including diabetic retinopathy, glaucoma, and macular degeneration. Knowledge of the basic physiological properties of retinal glial cells and their
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interactions with retinal neurons will add to our understanding of how these cells contribute to retinal pathology. The research outlined in this application will provide significant progress towards this goal. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HIF-1 AS A THERAPEUTIC TARGET IN DIABETIC RETINOPATHY Principal Investigator & Institution: Ihnat, Michael A.; University of Oklahoma Hlth Sciences Ctr Health Sciences Center Oklahoma City, Ok 73126 Timing: Fiscal Year 2002; Project Start 16-SEP-2002; Project End 31-AUG-2007 Summary: Diabetic retinopathy is a major complication of diabetes and a leading cause of blindness. In its later stages this disease is characterized by a hyperproliferation of retinal blood vessels, or angiogenesis. Hypoxia inducible factor -1 (HIF-1) is a transcription factor that is rapidly induced in response to hypoxia and regulates the expression of several genes critical to angiogenesis and glucose regulation. HIF-1 has been shown to be significantly increased in the retina in response to hypoxia and to advanced glycation products (AGEs), altered macromolecules associated with diabetes. The overall hypothesis driving these studies is that inhibition of angiogenesis through the specific disruption of HIF-1 is a novel, early target for potentially controlling proliferative retinopathy. The goal of specific aim one is to target HIF-lalpha, a critical subunit of HIF-1, at the messenger RNA level through the use of ribozymes, or catalytic pieces of RNA. The goal of specific aim two is to find specific peptide inhibitors of the interaction between the HIF-1alpha and the HIF-1beta (ARNT) subunit using phage peptide display. Both the ribozymes and the peptides will be introduced locally into the retina using adenovirus. The effect of these agents on angiogenesis and on downstream targets of HIF-1 (VEGF, PAl-l) will be examined using an oxygen-induced mouse ischemia model. Using these molecular approaches we seek to define a role for HIF-1 in proliferative diabetic retinopathy and to determine whether this transcription factor represents a valid target for therapy in this disease state. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: HIGHER ORDER VISUAL PERCEPTION: LOW VISION IN ELDERLY Principal Investigator & Institution: Odom, James V.; Medicine; West Virginia University P. O. Box 6845 Morgantown, Wv 265066845 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2006 Summary: (provided by applicant): Low vision is a major health problem, especially among the elderly; reduced vision impairs their ability to navigate in their environment, impairs their ability to perform activities of daily living independently, and places them at greater risk for accidents and death. Relatively little research has been directed to understanding the visual control of mobility and daily behavior in older Americans with reduced vision. Almost none of the research that has been performed has examined higher order perceptual functions in the performance of tasks of daily living including mobility. Our long-range objective is to examine the impact of reduced vision on higher order perceptual abilities and the relationship of differences in higher order perception on the performance of simulated and real tasks of everyday living. In order to accomplish this long-range goal we have brought together a team of vision researchers, clinicians, and computer scientists. For the purposes of this small, pilot study grant application, our aims are more specific and restricted. One set of higher order variables that have been identified in the literature as particularly important in mobility are those related to the detection of optic flow and its components. However, we have been
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Diabetic Retinopathy
unable to find research related to low vision patients' abilities use optic flow for detecting heading or navigating in their environment. Our specific aim for this grant is to conduct a series of six experiments to provide data on the ability of patients with low vision to detect optic flow information. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HIGH-RESOLUTION IMAGING OF OCULAR MELANOMA AND RETINA Principal Investigator & Institution: Bartsch, Dirk-Uwe G.; Associate Professor; Ophthalmology; University of California San Diego La Jolla, Ca 920930934 Timing: Fiscal Year 2002; Project Start 01-FEB-2001; Project End 31-JAN-2004 Summary: (Applicant's Description): High-resolution imaging allows improved understanding of retinal disease and pathological conditions, particularly in prognosis of malignant choroidal melanoma, age-related macular degeneration, diabetic retinopathy, ocular complications of AIDS and glaucoma. The eye can only be regarded as a diffraction-limited optical system up to a pupil diameter of 3 mm. Standard retinal imaging technology uses a 3 mm imaging aperture to avoid the higher order aberrations of the outer cornea. However, if these higher order aberrations can be compensated, diffraction-limited imaging at 7 or 8 mm pupil diameter can be achieved. The numerical aperture of the diffraction-limited eye at 7 or 8 mm pupil will allow to visualize retinal detail that was previously not achievable in ophthalmology. To achieve this goal we plan to develop a wavefront sensor that will allow us to measure the existing aberrations of the measured eye. We will test it in an eye model, in animal eyes and in human eyes. The wavefront sensor will be attached to a fundus camera and scanning laser ophthalmoscopes. The second aim is to use an adaptive wavefront compensator to correct the aberrations in a feed-back loop setup. We will test the complete system of wavefront sensor and wavefront compensator in an eye model, in animal eyes and in human eyes. The wavefront compensator will be attached to a fundus camera and scanning laser ophthalmoscopes. The third aim is to used digital image processing to correct for the portion of the residual aberrations that could not be compensated with the adaptive wavefront compensator due to mechanical considerations. Our group has previous developed a wavefront sensor and wavefront compensator based on a micromachined membrane deformable mirror. Due to the limited number of electrodes, slow speed of our computer system and the mechanical stiffness of the membrane we were not able to completely correct all measured aberrations. Our preliminary work shows that the system is capable of allowing wavefront correction. In this study we plan to improve the acquisition speed of our wavefront sensor and wavefront compensator to allow rapid wavefront compensation. Our preliminary results have shown that even the best aberration compensation still suffers from residual wave aberrations. Since we can measure and characterize these aberrations, we can develop digital inverse filter based on our experience in image reconstruction to correct the acquired images. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: HUMAN ANGIOGENESIS
ALKALINE
PHYTOCERAMIDASE
CONTROL
OF
Principal Investigator & Institution: Mao, Cungui; Medical University of South Carolina P O Box 250854 Charleston, Sc 29425 Timing: Fiscal Year 2002; Project Start 26-SEP-2002; Project End 31-AUG-2007
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Summary: (provided by applicant): Angiogenesis, the process of formation of new capillaries from preexisting blood vessels, is essential for the proper organ development and tissue repair (1). However, uncontrollable angiogenesis may lead to pathologies such as chronic inflammation (2), diabetic retinopathy (3), rheumatoid arthritis (4), and growth of solid tumors (5). Our long-term goals are to define the role of human alkaline phytoceramidase (haPHC) in regulating angiogenesis and to develop this concept into a new strategy to treat angiogenesis-related diseases by targeting this enzyme, haPHC, a novel enzyme which the PI identified recently, cleaves phytoceramide to generate phytosphingosine (PHS), which is in turn phosphorylated to generate phytosphingosine-1-P (PHS-1-P) through the action of sphingoid base kinases (6). Our additional preliminary data demonstrate that 1) PHS-1-P protects human umbilical vein endothelial cells (HUVEC) from apoptosis induced by serum starvation and induces migration of HUVEC; 2) the levels of PHS-1-P are regulated by haPHC through controlling the generation of its precursor, PHS from phytoceramide; 3) haPHC mRNA is highly expressed in placenta in which angiogenesis occurs actively; and 4) downregulation of haPHC by antisense oligodeoxynucleotide (ODN) suppresses growth of HUVEC. These results suggest the hypothesis that haPHC regulates angiogenesis by regulating the levels of the potential angiogenic stimulator, PHS-1-P. Specific aim 1: to determine the role of the human alkaline phytoceramidase in growth and survival of human umbilical vein endothelial cells. Our hypothesis is that haPHC regulates growth and survival of endothelial cells by controlling the generation of PHS-1-P. To test this hypothesis, we will determine 1) whether up-regulation of haPHC, by adenovirusmediated transfection of sense cDNA, elevates the levels of PHS-1-P in HUVEC and results in cell proliferation whereas down-regulation of haPHC by antisense cDNA transfection reduces the levels of PHS-1-P and results in apoptosis and/or growth suppression of HUVEC; and 2) whether apoptosis and/or growth inhibition induced by the downregulation of haPHC is alleviated or suppressed by exogenous PHS-1-P. We expect that downregulation of haPHC will lower the level of PHS- 1-P and induce growth suppression and apoptosis of HUVEC, while exogenous PHS-1-P will suppress these effects of haPHC down-regulation. Specific aim 2: to determine mechanism of the human alkaline phytoceramidase action. In our preliminary studies, we demonstrate that haPHC 1) is highly expressed in placenta and heart and localized to the Golgi apparatus and endoplasmic reticulum; 2) hydrolyzes NBD-Clz-phytoceramide preferentially in vitro, and 3) is activated by Ca2+,but inhibited by sphingosine (6). These results support the hypothesis that haPHC has very restricted substrate specificity; its action is regulated by second messengers; and its expression is compartment and tissue specific. To test this hypothesis, we will purify haPHC and determine its substrate specificity using different phytoceramide analogs, effects of cations and lipids on its activity, its cellular localization, and tissue specific expression. We expect that the purified haPHC 1) prefers phytoceramide with a specific acyl chain as its endogenous substrate, 2) is activated by a physiologic concentration of Ca2+, but inhibited by a low concentration of sphingosine, 3) is localized to the Golgi apparatus and ER, 4) is highly expressed in tissues where angiogenesis actively occurs. Specific aim 3: to determine the role of the alkaline phytoceramidase in angiogenesis. Our hypothesis is that haPHC regulates developmental angiogenesis and vascularogenesis by regulating the generation of PHS-1-P. To test this hypothesis, we will disrupt the mouse alkaline phytoceramidase (maPHC) gene and analyze developmental angiogenesis and vascularogenesis in maPHC null versus wild type mice. We expect that the mice lacking maPHC will have insufficient angiogenesis, which may lead to abnormalities in embryonic development. These studies should validate our hypothesis that haPHC has an important role in angiogenesis in a definitive way.
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Diabetic Retinopathy
Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HYPERSPECTRAL IMAGING OF OXYGEN SATURATION IN THE ONH Principal Investigator & Institution: Khoobehi, Bahram; Professor; Ophthalmology; Louisiana State Univ Hsc New Orleans New Orleans, La 70112 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2006 Summary: (provided by applicant): The development of a non-invasive means of measuring oxygen saturation in the fundus of the human eye would be useful in the diagnosis and monitoring of numerous disorders, including diabetic retinopathy, arterial venous occlusion disease, and glaucoma. In these studies, a practical system to evaluate oxygen saturation in the retina and optic nerve head using a recent innovation, hyperspectral imaging, will be developed. The hyperspectral technique measures spectral changes within the visible and infrared spectra and provides information on the molecular state of hemoglobin. The hyperspectral imaging device will allow measurement - non-invasively and in real time - of reduction and/or elevation in tissue oxygenation. The distinct optical signature of biological materials such as oxyhemoglobin and deoxy-hemoglobin as a function of their reflectance spectra will enable determination of their relative concentrations. In recent years, reflectance oximetry has been developed for the non-invasive measurement of oxygen saturation changes in the vessels of the fundus using double, triple, and multiple wavelength reflectance imaging. The hyperspectral reflectance oximetry that will be employed in these studies will permit the first non-invasive measurement for oxygen saturation in the optic nerve head tissue, and the hyperpectral data to be collected will intrinsically include all of the multiple wavelength spectra obtained in earlier approaches. The new system will be tested in two specific aims: 1) hyperspectral imaging will be used to non-invasively evaluate the stimulus-response relationship between perturbations in intraocular pressure (lOP) (10-50 mm Hg) and oxygen saturation in optic nerve head tissues and in retinal artery/vein pairs for a graded series of hypoxic states, and 2) the same studies will be performed in eyes with early stage experimental glaucoma. With this new approach, it will be possible to determine how acute changes in lOP alone or in combination with chronic lOP elevation (glaucoma) affect the three distinct microcirculations of the optic nerve head (surface nerve fiber layer; prelaminar region; lamina cribrosa) independently and/or collectively. The proposed studies are motivated by the potential for clinical application of this innovative technology in the early diagnosis of and monitoring of therapy for ocular vascular diseases in which the associated hypoxia may eventually lead to loss of vision. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: IMAGING FOCAL HYPOXIA IN DIABETIC RETINOPATHY Principal Investigator & Institution: Maman, Anne-Marie; Oxygen Enterprises, Ltd 207 St. Mark's Sq Philadelphia, Pa 19104 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2004 Summary: (provided by applicant): Diabetic retinopathy is the leading cause of blindness in working age Americans. In these patients there is pathologic growth of new blood vessels in the inner retina. These poorly formed blood vessels burst, bleeding into the retina and obscuring vision. Current treatment for these patients is to detect the neovascular formations and ablate tissue around the vessels, intending to reduce or eliminate further angiogenic response. It is proposed that new blood vessels are formed
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in response to local tissue hypoxia, but it is not possible at this time to identify focal areas of hypoxia in the retina. Oxygen Enterprises has developed a safe, accurate and robust method that is capable of detecting focal hypoxia in tissues. Through this Phase I SBIR Grant, the company proposes to apply their technology to the understanding and measuring oxygen in the retina of the eye. Initial application will be in biomedical research. Longer term goals will be to apply this technology into clinical practice, allowing clinicians to diagnose and treat patients with diabetic retinopathy earlier and more effectively. The company proposes to develop a phosphorescence lifetime imaging system that will provide an opticalmethod for the clinician that yields a topographic map, clearly identifying focal areas of hypoxia and differentiating them from areas of normoxia. During Phase 1 the company proposes to synthesize gram quantities of a new Oxyphors (phosphor) for suitable for pre-clinical testing and to construct a minimally invasive imaging system for use in ophthalmological research. The imaging system will be assembled and adapted for measuring oxygen in the retina of two animal models, piglets and rats, and the existing imaging software will be revised into a technically competent and user-friendly operating system. Oxygen Enterprises' imaging system is expected to offer sensitive and specific detection and quantification of focal hypoxia in retinal tissue - which is anticipated to allow earlier and more accurate diagnosis of retinopathy - and a diagnostic system with high stability and reliability, providing a clear and unambiguous display of retinal pathology. Emphasis will be on making the system user friendly and on providing it at a reasonable cost. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IMPROVING THE QUALITY OF DIABETES EYE CARE Principal Investigator & Institution: Lee, Paul P.; Professor; Ophthalmology; Duke University Durham, Nc 27710 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2007 Summary: (provided by applicant): Up to 95 percent of the more than 6, 000 to 24, 000 new cases of blindness and the ten thousands of cases of visual impairment due to diabetes each year in the United States can be prevented. Most efforts to reduce the visual loss have focused upon raising the 50 percent rate of annual eye exams on the assumption that patients entering the eye care system will subsequently do well. However, new qualitative and quantitative data indicate that significant deficiencies exist in the competency (diagnostic accuracy and treatment patterns) and technical process quality of care (history taking and examination elements) of eye care providers. Community-Based optometrists and general ophthalmologists correctly staged the severity of retinopathy in our pilot study about a third of the time, while roughly 40 percent of both groups reported performing at least 60 percent of the recommended history and examination elements on patient visits. Our proposed study is a randomized controlled trial that seeks to compare to a control group the efficacy of two levels of structured interventions that directly address both competency and technical process quality. One intervention will be "low technology" with paper-based aids (posters with standard reference photos and structured visit forms). The Second "high technology" intervention uses similarly structured aids in a digital tool (PDA). The control group will be exposed to usual and customary continuing professional education and educational feedback. The proposed measures are readily implemented and are accepted by providers. Because the study encompasses both general (comprehensive) ophthalmologists and optometrists, it includes the major community providers of eye care for patients. Retina specialist will be excluded, since they provide the level of care that is the goal of improvement to be attained with these interventions. The insights
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Diabetic Retinopathy
from the study results should be applicable to other areas of diabetes care and health care in general. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: INDUCED DEGENERATION
APOPTOSIS
IN
AGE
RELATED
MACULAR
Principal Investigator & Institution: Ferguson, Thomas A.; Associate Professor; Ophthalmology and Visual Sci; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2002; Project Start 01-AUG-1999; Project End 31-JUL-2005 Summary: (Applicant's Description) Neovascularization is the major cause of vision loss in patients with age- related macular degeneration (AMD), diabetic retinopathy, and retinopathy of prematurity. AMD is the leading cause of blindness in the Western world in individuals over 60 years of age. Since a large proportion of the population is living well beyond this age, this is a significant threat to the quality of life in elderly people. In patients with AMD new vessel growth (angiogenesis) beneath the retina from the underlying choroid (choroidal neovascularization or CNV) is the major or cause of severe visual loss in these patients. We recently examined the role of apoptosis in controlling new vessel growth in the eye by examining the function of two molecules, Fas (CD95) and FasL (CD95L). Our studies revealed that FasL plays a significant role in controlling CNV, where FasL+ retinal pigment epithelial cells (RPE) prohibit the growth and development of new Fas+ subretinal vessels that damage vision. Studies described in this proposal are designed to thoroughly understand the role of Fas/FasL and apoptosis in the pathogenesis of AMD. We propose 5 aims. Aim 1 we will more completely evaluate the role of Fas/FasL in CNV in a mouse model using normal, Fas, and FasL defective mice. In Aim 2 we will study cell endothelial cells derived from the choroid and compare these to endothelial cells derived from other areas. We will examnine cell death, proliferation, and differentiation using in vitro models and characterize the role of the Fas antigen in these processes. Aim 3 will contains experiments to explore the function of FasL on RPE cells and determine how growth factors and MMP inhibitors can affect FasL function in these cells that are crucial in controlling CNV. Aim 4 will explore potential treatment modalities in CNV applying the knowledge we have gained concerning the regulation of FasL expression to the animal model. Finally, studies in Aim 5 will evaluate clinical specimens from patients AMD for Fas/FasL expression. Our studies should provide important insights into one of the leading causes of blindness in the western world. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: INTRACELLULAR GLYCATION AND DIABETIC COMPLICATIONS Principal Investigator & Institution: Brownlee, Michael A.; Anita and Jack Saltz Professor; Medicine; Yeshiva University 500 W 185Th St New York, Ny 10033 Timing: Fiscal Year 2002; Project Start 01-APR-1984; Project End 31-JUL-2006 Summary: The long-term objectives of the proposed work are to elucidate the mechanisms by which hyperglycemia-induced intracellular reactive oxygen species (ROS) produce diabetic retinopathy. The specific research proposed in this application will elucidate the role played by ROS-induced glyoxalase I substrates, which are precursors of intracellular advance glycation endproducts and mediators of hyperglycemia-induced angiopoietin-2 gene expression in retinal Muller cells. Specific Aim 1 will evaluate the effect of hyperglycemia-induced intracellular reactive oxygen
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33
species (ROS) on glyoxalase I substrates, advanced glycation endproducts derived from these substrates, and diabetic retinopathy in uncoupling protein-2 (UCP-2) knockout and glyoxalase I transgenic mice. Streptozotocin diabetes will be induced in UCP-2 knockout, glyoxalase I transgenic, and wild type mice. Retinal concentrations of intracellular oxidative stress products, ROS-induced glyoxalase I substrates, and glyoxalase-I substrate-derived AGEs will be determined in diabetic and non-diabetic mice. Retinopathy will be assessed by semi-quantitative RT-PCR and in situ hybridization at early time-points, and by quantitative morphology at late time-points. Specific Aim 2 will evaluate the effect of inhibition of hyperglycemia- induced ROS on glyoxalase I substrates, advanced glycation endproducts derived from these substrates, and diabetic retinopathy in uncoupling protein-2 (UCP-2) knockout, glyoxalase I transgenic, and wild type mice. Streptozotocin diabetes will be induced in UCP-2 knockout, glyoxalase I transgenic, and wild type mice. In selected groups of these animals, hyperglycemia-induced intracellular ROS will be inhibited by treatment with either MnTBAP or EUK8, structurally distinct SOD/catalase mimetic compounds. Retinal endpoints will be assessed as described in Specific Aim 1. Specific Aim 3 will characterize the mechanism of Angiopoietin 2 transcriptional control by glyoxalase I substrates in cultured primary retinal Muller cells. A hyperglycemia-responsive mouse angiopoietin-2-luciferase reporter vector has been constructed which contains 2.5kb 5'flanking sequence. Progressive deletions from the 5' end of the Ang-2 promoter will be constructed using restriction endonucleases or PCR methods. The glyoxalase-I substrate responsive region will be identified, and known transcription factor binding sequences altered by site- directed mutagenesis. EMSA will be performed with indicated consensus oligonucleotides from the glyoxalase-I responsive region. Supershift experiments will use commercially available antibodies. IP-westerns of cell extracts will be immunoblotted with antibodies to glyoxalase I-substrate- derived advanced glycation endproducts. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: LIVE MICROSCOPY AND CYTOMETRY IN VASCULAR BIOLOGY Principal Investigator & Institution: Lin, Charles P.; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): This is a multidisciplinary, collaborative research program bringing together investigators from several institutions to work across technology and disciplinary boundaries. The group shares a common interest in vascular biology, particularly in the eye, and specifically in the application of modern optical technology to answer critical questions related to vascular biology. The technology platform will be based on the scanning laser ophthalmoscope and the realtime in vivo confocal microscope previously developed at Schepens Eye Research Institute and at the Wellman Laboratories of Photomedicine. The existing technology will be enhanced with new development to improve image resolution, contrast, sensitivity, methods for quantification, and flexibility of imaging in living animals. Specific questions to be addressed include: 1. What are the cellular processes governing normal vascular development and stabilization? 2. What are the factors governing angiogenesis, Iymphangiogenesis, and immune cell trafficking? 3. What are the cellular mechanisms for the development of sickle cell and diabetic retinopathy? 4. Can we visualize early changes in the retinal pigment epithelium noninvasively in vivo? 5. Can we detect circulating cells in vivo without drawing blood? Is the number of circulating tumor cells a good predictor for tumor burden and response to therapy? Imaging at the
34
Diabetic Retinopathy
cellular level will enable biologists to study problems in living animals over time, gaining physiological insights beyond what can be obtained by classic static measurement (histology, immunocytochemistry, etc.), substantially reducing the number of animals required to answer these critical questions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: LONGITUDINAL OPHTHALMOLOGY
STATISTICAL
METHODS
FOR
Principal Investigator & Institution: Davidow, Amy L.; Prev Med and Community Health; Univ of Med/Dent Nj Newark Newark, Nj 07107 Timing: Fiscal Year 2002; Project Start 01-FEB-2001; Project End 31-JAN-2005 Summary: (Applicant's Abstract) The proposed project is a two year study to develop inferential and study design aspects of a linear statistical model appropriate to the analysis of longitudinal ophthalmologic data and to apply the improved model in a reanalysis of a data set obtained from the Early Treatment Diabetic Retinopathy Study (ETDRS). The relevant statistical model is the repeated-measures random effects/AR(l) model for continuous data due to Heitjan and Sharma. This model incorporates crosscorrelation between eyes and longitudinal correlation among measurements obtained from a single eye. The re-analysis of the ETDRS data set will consider the effects of aspirin on visual acuity measured continuously. A previously published analysis (ETDRS Report Number 8) analyzed a categorical version of visual acuity, ignoring longitudinal correlation and handling cross-correlation between eyes by analyzing eyes separately. The repeated measures random effects /AR(l) model has already been utilized by Heitjan and Sharma in a published study of intraocular pressure, using the expected information to perform statistical inference. Simulation studies have shown that it performs well in the balanced data case. Our first objective is to develop better inferential methods so as to 1) handle unbalanced (i.e., missing) data such as that arising when only one eye of two has the disease of interest and/or when the number of followup visits varies with subject, 2) control for the use of a possibly mis-specified variance structure, and 3) compensate for the use of estimated variance parameters in the standard error of the fixed effects, a procedure that may result in an underestimation of the standard error. This objective will be accomplished by the following: 1) replacing the expected information with the observed information, the observed information being a more reliable method of performing statistical inference in the presence of missing data, 2) using the robust (sandwich) variance estimator, a method that can control for a possibly mis-specified variance structure, and 3) approximating the degrees of freedom so as to control for the possibility of underestimated standard errors. Methodological advances will be incorporated into a computer package to be made available on the World Wide Web. Our second objective is to carry out power and sample size calculations for several different longitudinal ophthalmologic study designs, under various assumptions about the prevalence of bi-ocular versus uni-ocular disease, differential treatment allocation, loss-to-follow-up, and expected adherence to study treatment(s). The implications of treatments applied at the eye-level (e.g., photocoagulation) as well as systemically applied treatments (e.g., aspirin) on sample size, frequency of evaluation, and power will be considered. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MATRIX METALLOPROTEINASES AND DIABETIC NEPHROPATHY Principal Investigator & Institution: Thrailkill, Kathryn M.; Arkansas Children's Hospital Res Inst Research Institute Little Rock, Ar 72202
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35
Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-JUL-2006 Summary: (provided by applicant): Matrix metalloproteinases (MMPs) are a family of zinc-dependent proteinases that are involved in the breakdown and remodeling of extracellular matrix (ECM). Dysregulation of MMP activity has been implicated in many pathologic processes characterized by degradation of connective tissue matrices, including rheumatoid arthritis, periodontal disease and metastatic cancer. Recent studies both in vitro and in animal models of diabetes suggest that hyperglycemiamediated alterations in MMP secretion, activation or action may also contribute to the development of diabetes-related complications including diabetic retinopathy and nephropathy. Based on these findings one can hypothesize that the mesangial accumulation and renal hypertrophy characteristic of diabetic nephropathy may result from reduced matrix degradation caused by a hyperglycemia-mediated suppression of renal MMP activity. In fact, preliminary clinical data from our laboratory confirm that in children with type 1 DM, serum MMP-2 concentrations are suppressed in the face of uncontrolled hyperglycemia, yet normalize with near-normalization of blood glucose levels. In the present study, we propose to investigate the hypothesis that MMPs are involved in the pathogenesis of diabetic nephropathy by measuring concentrations of specific MMPs (MMP-2, -8 and -9), concentrations of the naturally occurring inhibitors of MMPs (Tissue Inhibitor of Matrix Metalloproteinases, TIMP-1 and -2), and concentrations of the MMP-activated growth factor, insulin-like growth factor-I (IGF-I) in the serum and urine of patients with type 1 DM. We will examine levels of MMPs, TIMPs, and IGF-I in these biologic fluids among diabetic patient subgroups, ages 14-40 years, chosen to represent various time points in the natural history of d abet c nephropathy. Moreover, we will examine the correlation between observed differences in MMPFl'lMP/IGFconcentrations and differences in glycemic control at the time of study, as indicated by HbA1 c measurements and concurrent (72 hour) Continuous Subcutaneous Glucose Monitoring (CGMS). We anticipate that this study will provide preliminary evidence to establish a link between dysregulation of MMP activity and the pathogenesis of nephropathy in type 1 DM. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MECHANISM NEOVASCULARIZATION
OF
MUTANT
TIMP-3
INDUCED
Principal Investigator & Institution: Tolentino, Michael J.; Ophthalmology; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 01-APR-2001; Project End 31-MAR-2006 Summary: (Applicant's Abstract) The main objective of this proposal is to provide Dr. Tolentino a mechanism for rigorous training both technically and conceptually in gene therapy and molecular biology. Dr. Tolentino's long term goal is to become an independent investigator focusing on understanding the molecular mechanisms and developing treatments for pathologic ocular neovascularization seen in blinding conditions such as macular degeneration and diabetic retinopathy. The training plan proposed is essential for Dr. Tolentino to successfully pursue these long-term goals. The broad long-term research objective of this grant proposal is to understand the biochemical mechanisms that lead to choroidal neovascularization (CNV). The development of CNV in age related macular degeneration (AMD) is the leading cause of blindness in the United States. Patients with Sorsby's fundus dystrophy, an autosomal dominant form of macular degeneration, have similar clinical findings to AMD including CNV. These patients have been found to have a mutation in the tissue inhibitor of metalloproteinase-3 (TIMP-3) gene. The specific aims of this study are:
36
Diabetic Retinopathy
Specific aim 1: To test the hypothesis that CNV induced by mutant TIMP-3 (mTIMP-3) is caused by loss of functionality or direct stimulation of angiogenesis by mTIMP-3. To accomplish this aim, mTIMP-3 transfected endothelial cell will be assayed for their ability to proliferate, form tubes and migrate to angiogenic stimuli in vitro. Sub retinal injections into normal and transgenic mice of adenovirus expressing mTIMP-3 will be performed to determine mTIMP-3's ability to cause sub retinal neovascularization in vivo. Specific aim 2: To test the hypothesis that upregulation of vascular endothelial growth factor (VEGF) and/or down regulation of pigment epithelial derived growth factor (PEDF) is involved in mTlW-3 induced CNV. Both mTIMP-3 transfected retinal pigment epithelial (RPE) cells and a transgenic mouse model with a human TIMP-3 mutation that develops CNV will be assayed for protein and mRNA upregulation using ELISA, northern blot, immunohistochemical and in situ hybridization techniques. Specific aim 3: To develop and test gene vectors expressing inhibitors of angiogenesis (angiostatin, endostatin, PEDF) and test their ability to inhibit subretinal neovascularization in the mutant transgenic mouse. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MECHANISMS OF EPITHELIAL ALTERATIONS IN DIABETIC CORNEA Principal Investigator & Institution: Ljubimov, Alexander V.; Director; Cedars-Sinai Medical Center Box 48750, 8700 Beverly Blvd Los Angeles, Ca 900481804 Timing: Fiscal Year 2002; Project Start 01-AUG-2001; Project End 31-JUL-2005 Summary: (provided by applicant): Diabetic retinopathy has been the leading cause of blindness in the United States since 1974. It is manifest by progressive changes in the microvasculature of the diabetic eye, leading to intravitreal hemorrhages, retinal edema, neovascularization, and detachments. Along with the retina, cornea, lens and iris are also affected by diabetes. Many diabetics suffer from diabetic keratopathy that includes recurrent erosions, epithelial fragility, abnormal wound healing and increased susceptibility to injury. Altered epithelial-stromal interactions and epithelial basement membrane (BM) defects likely contribute to diabetic keratopathy. Despite clinical importance of diabetic corneal disease, the molecular mechanisms of this complication are not understood. In our preliminary studies, the expression of many BM components and proteinases has been analyzed in normal and diabetic human corneas. We show that: 1. Diabetic retinopathy (DR) corneas have severely decreased epithelial BM immunostaining for laminin-1, laminin-10, nidogen-1/entactin, and for epithelial integrin alpha3 beta1; 2. Gene expression of BM proteins and integrin alpha3 beta1 is not changed in diabetic and DR corneal epithelium; 3. Gene and protein expression of matrix metalloproteinase (MMP)-10 increases in diabetic and DR corneal epithelium and stroma, and MMP-3 expression increases in diabetic and DR corneal stroma. The data suggest that major components of corneal epithelial BM are altered in diabetes and especially DR due to elevated activity of specific proteinases, e.g., of MMP-1O that is expressed in the epithelium. Our hypothesis is that corneal epithelial BM in diabetes and DR undergoes degradation by elevated proteinases, notably by MMP-10. Proteinase expression and activity may be stimulated by specific growth factors activated by diabetic microenvironment. These alterations may constitute the molecular mechanism of corneal epithelial abnormalities in diabetes. Specific Aim 1.To characterize the effect of MMP-10 on the integrity of corneal epithelial BM and integrin alpha3 beta1 and on wound healing in organ-cultured human corneas. Specific Aim 2. To identify by gene array analysis growth factors and cytokines abnormally expressed in diabetic and DR corneas and examine their effects on MMP-10 and wound healing in normal organ-
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37
cultured corneas. Specific Aim 3. To assess by gene array analysis the expression levels of various proteinases in diabetic, DR and normal human corneas. Identify and analyze additional proteinases with elevated expression in diabetic corneas. Specific Aim 4. To attempt blocking BM and integrin degradation in human diabetic and DR organ-culture corneas. Neutralizing antibodies to specific growth factors and proteinases (primarily, MMP-10), and various MMP inhibitors including clinically approved tetracyclines will be tested in organ-cultured corneas. These studies could lead to the development of novel therapeutics that would block the progression of diabetic keratopathy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MECHANISMS OF PAI-1 INDUCED ANTI-ANGIOGENESIS Principal Investigator & Institution: Mulligan-Kehoe, Mary J.; Surgery; Dartmouth College 11 Rope Ferry Rd. #6210 Hanover, Nh 03755 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2007 Summary: (provided by applicant): Endothelial cells lining the vascular wall are normally maintained in a differentiated, quiescent state by anti-angiogenic molecules. Pro-angiogneic molecules destabilize the quiescent endothelium into migratory, proliferative endothelial cells that form new capillary blood vessels. The steady turn over rate of the vascular endothelium is maintained by a tightly controlled balance of pro- and anti-angiogenic molecules that have cell survival and death functions, respectively. A shift in the balance can alter the turn over rate of the endothetium and disrupt vascular homeostasis. It has been shown that vascular endothelial growth factor (VEGF) has a role in atherosclerotic plaque development. This is supported by studies which show that angiogenesis is associated with increases in plasmin and metalloproteinase activity which increases plaque susceptibility to acute rupture or plaque destabilization. Several animal studies have shown a reduction in atherosclerotic plaque neovascularization and plaque growth after treatment with angiogenesis inhibitors. Plasminogen activator inhibitor-1 (PAl-1) is over expressed in the intimal layer in the atherosclerotic vessel wall in human coronary artery disease. This has led to one hypothesis that PAl-1 expression is a means of controlling localized plasminogen activators that contribute to extracellular matrix degradation and smooth muscle cell migration. We have constructed recombinant truncated PAl-1 (rPAI-1) proteins to examine the anti-angiogenic activity of PAl-1 in "inactive" conformations (absence of reactive center loop). One rPAI-1 protein, rPAI-123, has potent anti-angiogenic activity. The activity of rPAI-123 induces cleavage of plasmin into angiostatin and inhibits the bioavailability of VEGF. In this study, we will utilize rPAI-123 to: Aim I: Clarify the rPAI-123 interactions that induce cleavage of plasmin into angiostatin; Aim II: Determine if rPAI-123 inhibits VEGF release from heparan sulfate; and Aim Ill: Define the anti-angiogenic/pro-apoptotic signaling pathways in rPAI-123 treated aortic endothelial cells. Due to the potent anti-angiogenic activity of rPAI-123 protein, it may ultimately play a useful role in the treatment of diiseases characterized by excessive angiogenesis, such as progression and stabilization of atherosclerotic plaques, diabetic retinopathy, and certain types of cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: MECHANISMS OF PHOTORECEPTOR DEATH IN PHOTIC INJURY Principal Investigator & Institution: Dunaief, Joshua L.; Assistant Professor; Ophthalmology; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 01-JUL-2000; Project End 31-MAY-2005
38
Diabetic Retinopathy
Summary: Age related macular degeneration, the most common cause of blindness among people aged 50 and older in the United States, results in photoreceptor degeneration. Similarly, retinitis pigmentosa, retinal detachment and ischemic diabetic retinopathy all lead to photoreceptor death. The loss of photoreceptors is the ultimate cause of significant visual loss. The mechanism of photoreceptor degeneration in these diseases is poorly understood, but is known to occur through apoptosis. This programmed cell death is a highly ordered and regulated cellular suicide pathway that has been well defined in lymphocytes. This application proposes to draw from the rich knowledge of apoptosis in lymphocytes to elucidate mechanisms of photoreceptor cell death in the photic injury animal model of retinal degeneration. This model has been studied extensively at the cellular but not yet at the molecular level. Good evidence suggests that photoreceptor degeneration in this model occurs through apoptosis. The ability of anti-apoptotic genes expressed in transgenic mice to inhibit photic injury induced cell death will be tested. Specifically, the ability of anti-oxidant genes and antiapoptosis genes that act upstream or downstream in apoptosis pathways to inhibit photoreceptor degeneration will be evaluated. Further, the intracellular localization of cytochrome c, a mediator of apoptosis, and the role of caspase activation will be probed. Caspases are proteases involved in a number of apoptotic pathways. These studies will define critical apoptotic pathways and suggest therapeutic interventions for the blinding disorders that result from photoreceptor degeneration. The proposed study is well within the realm of feasibility. The principal investigator has experience with molecular biology, transgenic mice and retinal histology. The mentor is an international leader in the molecular mechanisms of apoptosis, and the co- mentor has extensive experience with transgenic mouse models of retinal disease and gene therapy. This proposal should serve as a good launching pad for the PI's career devoted to understanding the molecular basis of photoreceptor degeneration. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MICROENVIRONMENT OF THE RETINA Principal Investigator & Institution: Linsenmeier, Robert A.; Professor; Biomedical Engineering; Northwestern University 633 Clark Street Evanston, Il 60208 Timing: Fiscal Year 2002; Project Start 01-JUL-1983; Project End 31-JUL-2007 Summary: (provided by applicant): The long-term objectives of this work are to understand aspects of the retinal microenvironment related to oxygen and pH, and how these relate to energy metabolism and function of the mammalian retina in vivo. While this work will be done in animals, it is particularly relevant to blinding diseases that affect the relationships between the circulation and retinal neurons in humans. During the next project period, our main interests are in diabetic retinopathy, retinal detachment, and retinal arterial occlusive disease. However, the results will also provide fundamental information that may be relevant to other types of retinal dysfunction. The proposed work will be done primarily on intact anesthetized cats, since their retina provides a good model for much of the human retina. The techniques are primarily to use oxygen and pH sensitive microelectrodes to map out retinal oxygen levels, pH and electrical activity (the electroretinogram) with high spatial and temporal resolution, as we have done previously under other experimental conditions. Following the measurements, mathematical modeling of diffusion will be used to extract metabolic parameters that are not apparent from the measurements alone, and to perform simulations of situations that may not be amenable to experimentation. Some measurements of retinal histology will also be made. The project has 5 specific aims. 1) We will study intraretinal oxygenation following photocoagulation, because the
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39
mechanism by which photocoagulation blocks neovascularization is still unclear. 2) We will use information about oxygenation after photocoagulation from specific aim 1 to create an appropriate two-dimensional diffusion model of this situation, with the hope of providing a better rationale for the density and size of lesions designed to treat retinopathy. 3) We will study retinal oxygenation in the detached retina in order to understand the basis for the protective effect of hyperoxia in retinal detachment, which has been shown recently in cats. 4) We will study pH after retinal arterial occlusion, to understand the potential role of acidosis in damaging the retina. 5) We will investigate the influence of anesthesia on the metabolic measurements we make, and will study metabolic differences between the cat and primate retinas. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOLECULAR AND CELLULAR MECHANISMS OF VASCULAR ANOMALIES Principal Investigator & Institution: Olsen, Bjorn R.; Hersey Professor of Cell Biology; Oral and Developmental Biology; Harvard University (Medical School) Medical School Campus Boston, Ma 02115 Timing: Fiscal Year 2003; Project Start 15-SEP-2003; Project End 31-MAR-2008 Summary: (provided by applicant): This Program Project, entitled '"Molecular and Cellular Mechanisms of Vascular Anomalies," represents the concerted and collaborative efforts of three research groups, two in Boston and one in Brussels, Belgium, to elucidate the causes and abnormal mechanisms that are responsible for vascular anomalies in the skin. Commonly called birthmarks, these anomalies include infantile hemangioma, a vascular tumor found in 5-10% of Caucasian children at 1 year of age, and vascular malformations. Hemangiomas usually appear a few days after birth, grow rapidly for a few weeks to months, and then slowly regress over a 5-10 year period. In most cases, no treatment is needed, but sometimes vital, structures can be obstructed or distorted causing serious problems. In contrast to hemangiomas, malformations do not regress, but grow with the child, and can become life-threatening. The investigators have recently found that hemangiomas contain clonal expansions of abnormal endothelial cells, and they have discovered two types of mutations that cause localized abnormalities in the skin of patients with venous malformations and glomuvenous malformations. In three research Projects, supported by three Cores, the Program investigators propose to examine and test the hypotheses that hemangiomas result from somatic mutations in genes that control endothelial cell proliferation and/or maturation from precursor cells, causing rapid growth of abnormal capillaries. In addition to identifying such genes and mutations, it is also proposed to identify genes responsible for rare cases of inherited hemangiomas and to establish mouse models allowing further studies of detailed pathological mechanisms. Finally, they now propose to generate mouse models for venous and glomuvenous malformations, characterize the cellular and molecular consequences of the causative mutations, and search for mutations in additional families. The proposed studies should lead to a better understanding of the pathogenesis of hemangiomas and malformations and therefore a basis for development of effective therapies. In addition, a better understanding of the causes and mechanisms of vascular anomalies will provide novel insights into blood vessel formation and growth. This will add significantly to the efforts to develop novel antiangiogenic therapies for cancer, diabetic retinopathy, and rheumatoid arthritis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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•
Diabetic Retinopathy
Project Title: MOLECULAR ANGIOGENESIS
MECHANISMS
OF
MEKK3-SIGNALING
IN
Principal Investigator & Institution: Su, Bing; Associate Professor; Immunology; University of Texas Md Anderson Can Ctr Cancer Center Houston, Tx 77030 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2007 Summary: (provided by applicant): Angiogenesis is essential for normal physiological processes such as organ development and wound healing. It is also critical to pathological processes such as tumor growth, atherosclerosis, rheumatoid arthritis, and diabetic retinopathy. Therefore, blocking angiogenesis could be a powerful therapeutic intervention for treating diseases requiring formation of new blood vessels. However, the underlying molecular mechanism of intracellular signal transduction in this process remains largely unexplored. We recently generated Mekk3-knockout mice through homologous recombination and demonstrated that MEKK3, a Ser/Thr protein kinase belonging to the mitogen-activated protein kinase (MAPK) kinase gene family, is essential for angiogenesis. The long-term goals of this study are to elucidate the molecular mechanisms of angiogenesis regulated by MEKK3 signaling. Our SPECIFIC AIM 1 is to determine the function of MEKK3 in endothelial cells (ECs) during embryonic development by examining the morphology, proliferation and apoptosis of ECs in the E8.5 to E10 wild-type, Mekk3+/- and Mekk3-/- fetuses. We will also isolate embryonic ECs from the E9-E9.5 fetuses and establish EC lines by using polyoma middle T antigen to transform the primary cultures. In SPECIFIC AIM 2, we will determine whether MEKK3 is a specific upstream activator of JNK1/2, ERK1/2, p38 and ERK5 MAPKs in ECs by using in vitro kinase assays. We will determine whether the induction of these MAPKs is defective in Mekk3-/- embryos, purified ECs and EC lines. In addition, we will determine whether MEKK3 is specifically activated by angiogenic stimulation by using in vitro kinase, in-gel kinase and MEKK3 phosphorylation assays. Furthermore, we will isolate and clone MEKK3-associated proteins by coprecipitation, chromatography, and yeast two-hybrid screening. In Specific Aim 4, we plan to generate Mekk3 floxed ES cells and mice, and use these mice to create EC-specific Mekk3 knock out (Mekk3 (EC-null)) mice and Mekk3-deficient ECs with Cre recombinase. Function of MEKK3-signaling will be studied specifically in ECs using these mice. In addition to revealing the MEKK3-signaling in angiogenesis, the outcome from this study will provide conceptual and material resources for studying MEKK3 and its homologues in many other physiological and pathological processes. Most importantly, this study may discover novel molecular targets for therapeutic intervention for treating diseases requiring formation of new blood vessels like cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MONOCYTE COMPLICATIONS
VEGF
&
PKC,
MARKERS
FOR
DIABETIC
Principal Investigator & Institution: King, George L.; Professor and Research Director; Joslin Diabetes Center Boston, Ma 02215 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-JUL-2004 Summary: (provided by applicant): Hyperglycemia is the major cause of diabetic microvascular complications including retinopathy, nephropathy and neuropathy. Early diagnosis of microvascular complications in these tissues has been difficult due to the long duration of disease required for the onset of clinical symptoms and the general inaccessibility of vascular and neurological tissues for analysis. Animal studies have clearly demonstrated that microvascular pathologies in the retina and renal glomeruli
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can manifest years before the onset of clinical symptoms. Activation of protein kinase C (PKC), specifically the B isoforms and increases in VEGF levels in the retina and renal glomeruli have been shown to correlate with severity of hyperglycemia induced vascular pathologies in diabetic animals. However, due to tissue access problems, almost all of the data regarding the increases in PKC activities and VEGF levels have been measured in vascular tissues from animal models of diabetes. Plasma levels of PKC do not exist and plasma VEGF levels do not consistently correlate with corresponding levels in the microvascular tissues. Recently, we have measured PKC activities in the circulating mononuclear cells and they correlated with the severity of diabetic retinopathy and nephropathy in type 1 and 2 diabetic patients. In addition, the expression of VEGF levels in the circulating monocytes from humans and diabetic rats can be increased by PKC activation. Similarly, increases in PKC activation and, potentially, VEGF expression in the circulating monocytes responded in parallel to diabetes in the vascular tissues of retina, renal glomeruli and arteries. In addition, monocyte activation has been noted by multiple studies in the cardiovascular and microvascular circulations including the retina and renal glomeruli from diabetic animals. Thus, we are proposing to test the hypothesis that increases in PKC activation and VEGF levels in the circulating monocyte are similar to those found in the retina and renal glomeruli in response to hyperglycemia or diabetes. Therefore, the ability to measure VEGF levels and PKC activities in circulating monocytes, which can be easily accessed, could be used as surrogate markers of diabetic microvascular disease especially diabetic retinopathy and nephropathy. We are proposing to test three specific aims in diabetic and control patients 1) To correlate VEGF levels with PKC activity in circulating monocyte with severity of retinopathy and nephropathy. 2) To determine whether glycemic control can alter the activation of PKC and VEGF levels in circulating monocytes. 3) To correlate PKC activity and VEGF levels in circulating monocytes with VEGF level in the ocular fluids obtained during surgery. These data can provide definitive evidence to determine whether further studies are needed to establish these two parameters in the circulating monocyte as surrogate markers of diabetic microvascular diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NEUROTRANSMITTER TRANSPORTERS IN THE RETINA Principal Investigator & Institution: Sarthy, Vijay P.; Magerstadt Professor; Ophthalmology; Northwestern University Office of Sponsored Research Chicago, Il 60611 Timing: Fiscal Year 2002; Project Start 01-AUG-2000; Project End 31-JUL-2004 Summary: (Adapted from applicant's abstract): As the premier excitatory synaptic transmitter, glutamate has the potential to influence the function of most neuronal circuits in the retina. In addition, glutamate can also act as a potent neurotoxin when present at a high level in the retinal microenvironment. Therefore, extracellular glutamate needs to be maintained at a low level to ensure a high signal-to-noise ratio for glutamatergic neurotransmission and to protect neurons from excitoxic damage and cell death. The long-term objective of the proposed project is to identify mechanisms that operate to maintain glutamate levels in the retina. Extracellular glutamate level is normally kept low by the action of potent uptake systems present in retinal neurons and Muller (glial) cells, and inadequate clearance of glutamate may result in excitotoxic neuronal loss. Although glial glutamate transporters are known to play a major role in glutamate uptake, their specific contribution to glutamate homeostasis has not been directly examined because glial-specific, glutamate uptake inhibitors are not available.
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Diabetic Retinopathy
Mice with targeted disruption of glial glutamate transporter genes, GLT-1- and GLAST, provide an alternative means to investigate the function of glial glutamate transporters. The present proposal is concerned with neurochemical and immunolocalization studies in GLAST-knockout mice, and tests the hypothesis that GLAST plays a crucial role in regulating retinal glutamate levels, and in metabolic trafficking in the retina. The specific goals of the proposal are to determine whether normal metabolic signaling, and metabolite transfer from Muller cells to photoreceptors is disrupted by loss of GLAST; to examine whether GLAST-deficiency provokes compensatory changes in other glutamate transporters; to determine whether intracellular and extracellular glutamate levels are altered in GLAST-knockout mice; to determine whether NMDA and AMPA glutamate receptor expression is modified in GLAST-null mice; and finally to examine whether loss of GLAST leads to major changes in GABAergic neurons in the retina. Because extracellular glutamate levels have been reported to be elevated in glaucoma and diabetic retinopathy, the proposed studies are crucial for elucidating the cellular mechanisms responsible for elevation in glutamate levels in the retina, and for considering glutamate transporters as potential therapeutic targets. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NEW STATISTICAL METHODS FOR DEMOGRAPHIC DATA ANALYSIS Principal Investigator & Institution: Wahba, Grace; Bascom and I.J Schoenburg Professor of s; Biostatistics/Med Informatics; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2002; Project Start 01-DEC-1992; Project End 31-DEC-2002 Summary: (Adapted from the Applicant's Abstract): This research is for the further development of a new class of multi variate semi-parametric model building methods' known collectively as Smoothing Spline Analysis of Variance, (SS-ANOVA) which are suitable for the analysis of data from large cohort studies, either epidemiologic or clinical trials, with many qualitatively different variables observed over several time points. These methods represent an attempt to obtain flexible empirical relationships between multiple complex responses and predictors. If such models can be fitted to the data, then estimated sensitivities of the responses to various predictors can be obtained and the existence of associations between various variables of interest can be tested. The models reduce to standard parametric models if the data suggest that nonparametric terms in the model are not present. SS-ANOVA models have been built and tested for the prediction of multi variate and multi categorical responses and methods developed which allow the analysis of large complex data sets. The investigators will extend this work in several directions: Development of methods to prescreen large, complex data sets for patterns of relationships that warrant further examination; more sophisticated model selection methods, extension to nonparametric multi variate density estimation for the purpose of uncovering conditional and time dependent relationships among the variables, and the development of threshold models. Data from the Wisconsin Epidemiological Study of Diabetic Retinopathy and the Beaver Dam Eye Study will be used to examine the models under study for their reasonableness and for their ability to answer questions meaningful to the study scientists. The results will have broad applicability to other large epidemiological studies as well as to clinical trials. The research software will be developed into a user friendly form, documented, and made publicly available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: NON-COX ANGIOGENESIS
ARACHIDONIC
ACID
METABOLITES
43
AND
Principal Investigator & Institution: Rao, Gadiparthi N.; Associate Professor; Medicine; University of Tennessee Health Sci Ctr Memphis, Tn 38163 Timing: Fiscal Year 2004; Project Start 01-APR-2004; Project End 31-MAR-2008 Summary: (provided by applicant): Inflammation that follows tissue injury is believed to be important in the initiation and progression of various diseases including, atherosclerosis, cancer, and retinopathy. Phospholipase A2s (PLA2s), a group of enzymes that breakdown phospholipids generating arachidonic acid and lysophospholipids have been implicated in inflammation. One of the major events underlying the progression of atherosclerosis is angiogenesis. Endothelial cell (EC) migration and proliferation are critical events in angiogenesis. Emerging evidence suggests that PLA2, arachidonic acid and its eicosanoid metabolites play a role in the regulation of cell migration, proliferation, and apoptosis. In addition, recent investigations using nonsteroidal anti-inflammatory drugs reveal a potential role for eicosanoids in angiogenesis. Based on this knowledge, we hypothesize that eicosanoids, particularly the lipoxygenase-monooxygenase metabolites of arachidonic acid, play an important role in angiogenesis and thereby influence the pathogenesis of atherosclerosis. To test the role of eicosanoids in angiogenesis we will address the following four specific aims: 1. To identify eicosanoids produced in human microvascular endothelial cells (HMVEC) and determine their effects on angiogenesis using in vitro and in vivo models. 2. To determine the effects of angiogenic eicosanoids on HMVEC migration and proliferation. 3. To test the role of the Jak/STAT and PI3K/Akt pathways in angiogenic eicosanoid-induced HMVEC migration and proliferation. 4. To identify the effector molecules of eicosanoid-induced angiogenesis and study the mechanisms underlying their regulation of expression in HMVEC and vascular smooth muscle cells. The results of this proposal will provide novel information on the identification of specific angiogenic eicosanoids and on elucidation of the underlying mechanisms by which these lipid molecules stimulate angiogenesis. Such knowledge, in turn, could be useful in developing therapeutics in the prevention of progression of diseases such as atherosclerosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NONPEPTIDE SOMATOSTATIN AGONISTS FOR RETINOPATHY Principal Investigator & Institution: Shapiro, Gideon; Somatocor Pharmaceuticals, Inc. Ste 125 Alachua, Fl 32615 Timing: Fiscal Year 2003; Project Start 01-FEB-2003; Project End 31-JAN-2004 Summary: (provided by applicant): Diabetic retinopathy (DR) is the leading cause of blindness in the United States. The disorder is characterized by aberrant neovascularization ultimately leading to blindness. Currently, there is no drug treatment for DR patients and pannretinal laser coagulation surgery is the only option to delay blindness. Somatostinergic drugs are growth factor inhibitors that offer the potential to treat a probable cause of diabetic retinopathy by blocking key mediating steps in disease progression. Clinical trials with somatostatin peptide drugs in DR patients indicate that somatostatinergic drug therapy can stop neovascularization and improve visual acuity. However, the clinical results have been highly variable and have been best for patients receiving high dosage regimens or continuous parenteral treatment. These results are consistent with an inadequate blood-retinal barrier penetration of somatostatin peptide drugs to reach target retinal tissues. New non-
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Diabetic Retinopathy
peptide lipophilic somatostatin receptor agonists described herein have the potential to effectively penetrate the BRB. Using pharmacological in vitro and animal testing models of DR this study aims to establish structure activity relationships for this innovative class of compounds. The final goal is to identify a small potent somatostinergic molecule that readily accesses target retinal tissue for clinical testing in DR patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NOVEL TOMOGRAPHY
DIAGNOSTICS
WITH
OPTICAL
COHERENCE
Principal Investigator & Institution: Fujimoto, James G.; Professor of Pharmacology; Center for Cancer Research; Massachusetts Institute of Technology Room E19-750 Cambridge, Ma 02139 Timing: Fiscal Year 2002; Project Start 01-SEP-1985; Project End 31-MAY-2005 Summary: (Adapted from applicant's abstract): This is a collaborative multi-disciplinary program involving investigators at the Massachusetts Institute of Technology and the New England Eye Center. Optical Coherence Tomography (OCT) is an emerging technology for ophthalmic performance that can perform non-contact, non-invasive real time cross sectional imaging of the retina and the anterior eye. Standard ophthalmic OCT has a 10 micron axial resolution, ten times higher than conventional ultrasound. Our objective is to develop new OCT technology, which achieves a quantum leap in performance over current ophthalmic OCT and to demonstrate this technology for the early diagnosis and monitoring of disease of the retina and anterior eye. We will increase OCT axial image resolution by 5 to 10 times from 10 microns to about 1-2 microns. And also develop multi-wavelength, spectroscopic OCT techniques to improve differentiation of morphology and permit micron scale functional imaging. Our hypothesis is that these advances will dramatically enhance ability to image structural morphology such as intraretinal features, as well as improve the accuracy in reproducibility of morphometric measurements such as retinal thickness or nerve fiber layer thickness. We propose to: 1. Develop ultra high resolution OCT technology for imaging the retina and anterior eye. 2. Image transgenic retinal mouse models and cross sectional and longitudinal studies. 3. Perform cross sectional patient studies to investigate the capabilities of ultra-high resolution OCT for identifying micro-structural changes associated with posterior segment diseases. 4. Investigate ultra high resolution OCT for improving the accuracy of morphometric imaging of retinal thickness and nerve fiber layer thickness. 5. Investigate imaging structures in the anterior eye at the cellular level. 6. Perform preliminary clinical studies to investigate the ability of ultra high resolution OCT to identify ocular pathologies in the anterior eye segment. 7. Develop and demonstrate spectroscopic OCT techniques enabling spectrally resolved tomographic imaging on the micron scale. 8. Demonstrate spectroscopic OCT imaging of oxygen saturation in retinal and choroidal vasculature. 9. Perform preliminary clinical studies to assess the effectiveness of ultra high resolution structural, morphometric, or spectroscopic OCT imaging to diagnosis and monitor the progression of retinal disease. This proposal involves the development of new instrumentation which will have wide spread research and clinical applications as well as the development and validation of methods for the early diagnosis and monitoring of diseases including AMD, glaucoma, and diabetic retinopathy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: OPTIMIZED RETINAL CAMERA Principal Investigator & Institution: Truitt, Paul W.; Kestrel Corporation 3815 Osuna Ne Albuquerque, Nm 87109 Timing: Fiscal Year 2003; Project Start 01-APR-2000; Project End 31-MAY-2005 Summary: (provided by applicant): A low-cost, high-resolution, high-contrast color digital camera optimized for ophthalmology will be demonstrated. This Optimized Retinal Camera will be specifically tested for its effectiveness in meeting the image quality requirements for the screening and assessment of pre-proliferative and proliferative diabetic retinopathy in both traditional clinical settings and in telemedicine. The proposed device exploits recent technological advances in high sensitivity charge coupled device (CCD) cameras and digital signal processing electronics. Today's CCD cameras do not have the dynamic range to image the human retina. The human retina is characterized by regions of high reflectivity (20-40 percent), such as the optic disc, and very low reflectivity (<2 percent), such as the macula and fovea. Further, these existing digital cameras treat each of the color channels in the same manner and do not consider the special, red-saturated characteristics of the retina. The approach builds on existing fundus imaging technology developed by Kestrel for the National Eye Institute. The proposed Optimized Retinal Camera will be shown to offer significant improvement over existing digital color cameras by addressing each of the deficiencies mentioned above. Joslin Diabetes Center, the University of Iowa Department of Opthalmology, and the University of New Mexico Health Sciences Center will provide independent, "masked" evaluation of the optimized digital retinal images. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PARACRINE REGULATION OF ANGIOGENESIS BY MURAL CELLS Principal Investigator & Institution: Nicosia, Roberto F.; Professor; Pathology; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2002; Project Start 01-APR-1995; Project End 31-MAR-2006 Summary: Angiogenesis plays a critical role in the revascularization of ischemic organs and in the progression of cancer, atherosclerosis, rheumatoid arthritis, and diabetic retinopathy. The outcome of angiogenesis depends on neovessel survival. Developing vessels uses the angiopoietin/Tie2 system to acquire a stabilizing layer of mural cells (smooth muscle cells/pericytes). The mechanisms regulating this process are, however, poorly understood because the Tie2 receptor is reportedly expressed in endothelial cells but not in mural cells. Using the rat aorta model of angiogenesis we found that Tie2 is transiently expressed in intimal- derived mesenchymal cells that have the capacity to differently into mural cells. Tie2+ mural precursor cells migrate and secrete matrix metalloproteinases in response to Ang-1 which they produce, and Ang-2, which is produced by endothelial cells. Based on the additional observation that the intimal/subintimal layers of the rat aorta contain Flk- 1+ and Tie2+ non-endothelial mesenchymal cells and have angioinformative properties we postulate that Tie2+ muralprecursor cells arise from vascular progenitor cells capable of both endothelial and mural cell differentiation. We linked mural cell recruitment to the p38 MAPK signaling pathway by demonstrating that pharmacologic inhibition of p28, which is activated upon Tie2 stimulation, abrogates mural cell development resulting in naked neovessels. Based on these observations the specific aims of this grant focus on the following hypotheses. 1) The aortic wall. contains vascular progenitor cells capable of both endothelial and mural cell differentiation. 2. The muscular wall of blood vessels
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Diabetic Retinopathy
originates from Tie2+ mural precursor cells. 3. Mural cell recruitment during angiogenesis is selectively mediated by the p38 MAPK pathway. Vascular progenitor cells of neonatal, young and old rat aortas will be identified by immunohistochemistry and confocal microscopy and isolated by surface marker-based magnetic beads technology. Their angioformative and mural cell differentiation properties will be studied in models of vascular organ culture, microvessel assembly and chemotaxis. The role of Tie2 and p38 MAPK pathway in mural cell recruitment will be studied by gene transfer technology using adeno-associated viral vectors carrying wild type or dominant-negative genes Mural cell recruitment will be analyzed by Immunohistochemistry, confocal microscopy and image analysis. Gene/protein expression and function will be evaluated by Northern and Western analysis, RT-PCR, kinase assays, gel zymography, in situ hybridization, and immunohistochemistry,. These studies will define key cellular and molecular mechanisms of vessel wall development. This knowledge may lead to novel approaches for the stabilization of neovessels in ischemic conditions, the induction of vascular regression in angiogenesisdependent disorders, and the bioengineering of blood vessels for therapeutic applications. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PATHOGENIC RETINOPATHY
MECHANISMS
UNDERLYING
DIABETIC
Principal Investigator & Institution: Medof, M Edward.; Pathology; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2004; Project Start 15-JUN-2004; Project End 31-MAY-2008 Summary: (provided by applicant): The pathogenic processes that give rise to microangiopathic retinopathy and other vascular complications in diabetes are poorly understood. Several new lines of evidence have pointed toward inflammation as playing a heretofore unrecognized role. Retinal cells and vasculature and other self cells are protected from attack by autologous complement proteins by a set of intrinsic membrane regulatory proteins. These regulators are the decay accelerating factor (DAF or CD55), the membrane cofactor protein (MCP or CD46), and the membrane inhibitor of reactive lysis (CD59). Previous studies from our lab have shown that all three surface proteins are highly expressed in the retina and its associated vasculature in levels similar to those on glomerular cells and on systemic vasculature, sites where intrinsic regulatory activity is critical. In recent in vitro work, we have shown that DAF's regulatory function is 1) >90% inactivated by incubation with glucose or ribose, 2) rapidly abrogated by methylglyoxal incubation, and 3) lost due to modification of one or more active site lysine and arginine residues, the latter to argprymidine. In in vivo work, we have shown that endogenous DAF protein isolated from diabetic retinas is modified by several sugar adducts including argpyrimidine. The proposed studies are directed toward 1) determining the functional effects of chemical modifications in DAF, MCP, (and CD59) that are induced by hyperglycemia and other metabolic abnormalities that pertain in the diabetic state, 2) structurally characterizing the types and sites of the modifications on the regulators, 3) analyzing the functions and structures of endogenous DAF, MCP, (and CD59) proteins isolated from retinas and other tissues of diabetics, and 4) examining whether the pathological changes that are associated with retinopathy and other diabetic complications develop more rapidly in Daf1-/- (murine DAF homolog), Crry-/- (murine MCP surrogate), CD59a-/- (murine CD59 homolog) and double Daf1-/- / -/- Curry-/- or Daf1-/- / CD59a-/- mice experimentally made diabetic with streptozotocln. Since vasculopathy and retinopathy are debilitating
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complications that eventually affect most patients with diabetes, fully understanding the mechanisms involved in their development is important in designing effective therapeutic interventions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PHYSIOLOGY OF RETINAL PERICYTES Principal Investigator & Institution: Puro, Donald G.; Ophthalmology and Visual Sciences; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002; Project Start 01-APR-1999; Project End 31-MAR-2007 Summary: (provided by applicant): Our long-range objective is to elucidate the pathophysiological mechanisms that disrupt microvascular function early in the course of diabetic retinopathy. A vital function lost soon after the onset of diabetes is the autoregulatory control of the retinal microcirculation. The resulting inefficiency in the distribution of blood flow compromises the function, and eventually, the viability of retinal neurons, glia and vascular cells. At present, a critical gap in our understanding of how diabetes alters microvascular function is the limited knowledge of the mechanisms by which local vasoactive signals regulate capillary perfusion in the retina. Our proposed studies are based on a new working hypothesis. Namely, voltage changes induced by vasoactive signals that act at distal capillary sites must be transmitted electrotonicly via gap junction pathways to proximal pericytes. This intercellular transmission is necessary because proximal, but not distal, pericytes contain the contractile apparatus necessary to regulate the diameter of the microvascular lumen. Using dual perforated-patch recordings and other techniques, we will compare intercellular communication within pericyte-containing microvessels freshly isolated from retinas of control and diabetic rats. To address the mechanisms by which diabetes disrupts distal-to-proximal communication within the retinal microvasculature, the specific aims of our proposed studies will test the hypotheses that (1) in diabetes a disruption of electrotonic transmission between retinal pericytes compromises the transduction mechanism by which a vasoactive signal acting at a distal capillary site elicits a contraction or relaxation of the proximal portion of a pericyte-containing microvessel, (2) PKC-beta isoforms play a critical role in the mechanism by which gap junction pathways are disrupted in microvessels of the diabetic retina and (3) ET/A endothelin receptors mediate disruption of intercellular communication within diabetic microvessels. Over the long-term, elucidating the mechanisms by which diabetes disrupts the ability of local vasoactive signals to regulate capillary perfusion will facilitate the development of new strategies to ameliorate, and hopefully, prevent sightthreatening complications of this disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: RECEPTORS
PILOT--CHEMICAL
PROFILING
OF
ORPHAN
NUCLEAR
Principal Investigator & Institution: Downes, Michael R.; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 15-AUG-2002; Project End 31-JUL-2007 Summary: A solid clinical rationale exists for the discovery of novel orphan nuclear receptor (ONR) therapeutic ligands. The intimate associate, for example, between PPARgamma and carbohydrate and lipid metabolism, for example, finds clear expression in a variety of metabolic and aging disorders from atherosclerosis and lipid
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Diabetic Retinopathy
metabolism, for example, finds clear expression in a variety of metabolic and aging disorders, from atherosclerosis and diabetes, to Alzheimer's disease, decreased skin elasticity, male erectile dysfunction, pulmonary fibrosis, and atherosclerosis, and ocular diseases such as diabetic retinopathy, glaucoma, cataract formation, and age-related macular degeneration (AMD). This proposal will focus on the discovery of novel chemical tools for the purpose of advancing ONR research. A technology platform will be assembled that will facilitate the screening of chemical compound libraries for molecules able to modulate ONR-mediated transcription. Chemical screens that will be established to achieve this objective will consist of both in vivo and in vitro bas assays developed specifically for a high throughput (HTS) 384 well format. The assays developed exploit the agonist induced association of receptor ligand binding domains (LBDs) with nuclear receptor co-regulators and their derivative peptides. Currently we have diverse 18000 chemical compound library of mostly synthetic compounds that we have demonstrated to be viable for screening against ONRs. A pilot a screen of these compounds against FXR and identified novel compounds that robustly activate transcription of this ONR. The major goal of this project is to identify potent, specific compounds and make them freely available to the academic community to contribute high quality and unrestricted research on ONR function. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: POST-DPP FOLLOW-UP STUDY Principal Investigator & Institution: Crandall, Jill P.; Medicine; Yeshiva University 500 W 185Th St New York, Ny 10033 Timing: Fiscal Year 2003; Project Start 15-AUG-1994; Project End 31-JAN-2008 Summary: (provided by applicant): The Diabetes Prevention Program is a multicenter controlled clinical trial examining the efficacy of an intensive life-style intervention or metformin to prevent or delay the development of diabetes in a population selected to be at high risk due to the presence of impaired glucose tolerance (IGT). Development of diabetes, defined by 1997 ADA criteria, is the primary outcome while cardiovascular disease and its risk factors are important secondary outcomes. The DPP began recruitment in mid-1996. At the time of this application, total study exposure is a mean of approximately 3 years (range 2 to 5) with a total of approximately 10,000 patient years in the 3,234 volunteers in the 3-arm study. On the basis of a statistically significant and clinically compelling decrease in the development of diabetes in the life-style intervention and metformin-treated groups (58% and 31% reductions, respectively) compared with the placebo treated group, the DPP Data Monitoring Board and NIDDK ended the masked treatment phase of the study in May, 2001, one year earlier than originally planned. This application is designed to take further advantage of the scientifically and clinically valuable cohort of DPP volunteers and the large volume of data collected during the study. The highly compliant DPP cohort, including 45% minorities, is the largest IGT population ever studied. Moreover, the subcohort that has developed diabetes (n approximately 700) has been followed from near the exact time of diabetes onset. Clinically important research questions remain in the wake of the DPP. The carefully collected, centrally measured and graded data in this cohort should help to answer, definitively, a number ofvolunteers with impaired glucose tolerance and volunteers whose diabetes developed during the DPP to determine the natural history of diabetic complications. This analysis will be epidemiologic in nature with all groups being pooled with prior treatment being used as a co-variate. Finally, the same data will be used to examine the effects of gender, age, and race/ethnicity on diabetes and its vascular complication.
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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PROTEIN PRODUCTION OF PEDF-POTENT ANTIANGIOGENIC AGENT Principal Investigator & Institution: Wei, Lisa L.; Genvec, Inc. 65 W Watkins Mill Rd Gaithersburg, Md 20878 Timing: Fiscal Year 2003; Project Start 01-MAY-2003; Project End 31-OCT-2003 Summary: (provided by applicant): Exudative age-related macular degeneration (AMD) and proliferative diabetic retinopathy (DR), due to aberrant choroidal and retinal neovascularization respectively, are two of the leading major causes of blindness in the US. PEDF (Pigment Epithelium-Derived Factor) is a potent endogenous antiangiogenic/neurotrophic factor and is purported to be the key natural regulator of vascularity in the eye. In experimental disease models, PEDF blocks choroidal and retinal neovascularization. Based on these compelling data, we hypothesize that administration of PEDF protein may treat blinding ocular neovascular diseases such as wet AMD. It will be the overall goal of the SBIR Phase II to generate preclinical data enabling potential clinical testing of PEDF protein. In this Phase I application, we will test the feasibility of generating PEDF for preclinical studies. We propose: 1) to generate reproducible stocks of high quality PEDF protein and 2) to demonstrate the biological activity/potency of the purified protein product. This bioactive recombinant human PEDF will be used for future PEDF pharmacokinetic studies, to test efficacy of purified PEDF protein in ocular disease models, to test various delivery approaches, and to determine whether PEDF-based product should be advanced to clinical testing. Furthermore, the methods and procedures generated in the Phase I SBIR grant may lead to future viable manufacturing processes and assays that could lead to clinical grade material. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: RACE AND LONG-TERM DIABETES SELF-MANAGEMENT IN AN HMO Principal Investigator & Institution: Ross-Degnan, Dennis; Harvard Pilgrim Health Care, Inc. 93 Worcester St Wellesley, Ma 02481 Timing: Fiscal Year 2002; Project Start 15-JAN-2002; Project End 31-DEC-2004 Summary: (provided by applicant): This project will examine the complex relationships between race, diabetes self-management (including self-monitoring of blood glucose and diabetes drug therapy), glycemic control, and diabetes complications in a managed care setting over a nine-year period. African Americans with diabetes are less likely to be in glycemic control, a major risk factor for development of complications, including nephropathy, retinopathy, and peripheral vascular disease. Randomized controlled trials suggest that diabetes self-management including patient education, drug therapy, changes in diet, and regular exercise can improve glycemic control in the African American population. However, there is little epidemiological evidence regarding the role of race/ethnicity as a determinant of adherence to recommended diabetes selfmanagement practices, or regarding the relationship between self-management, glycemic control, and subsequent clinical outcomes. Further, previous studies of race and diabetes self-management have been limited by short study periods, inadequate sample size, and reliance on self-reported measures of self-monitoring of blood glucose. The clinical setting for this study is Harvard Vanguard Medical Associates (HVMA), a large multi-site, multi-specialty group affiliated with Harvard Pilgrim Health Care.
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HVMA consists of 14 health centers serving over 300,000 people in the Boston area. We will use an open cohort design to enroll all adult (l8 years) patients between 1991 and 1999 who have 24 months or more of uninterrupted enrollment in HVMA following ascertainment of non-gestational diabetes, defined by (1) hospital discharge diagnosis of diabetes mellitus, (2) outpatient diagnoses of diabetes mellitus, HbAlc lab test result 8.0, or use of a diabetes drug (insulin, sulfonylurea, or metformin). We estimate that the cohort will include approximately 1,800 adults identified as African American and 5,000 identified as Caucasian. Access to HVMA computerized medical records, hospital emergency room and inpatient claims, lab, and pharmacy data will allow us to create reliable, objective measures of self-monitoring (home glucose monitor test strip use), drug therapy. glycemic control (HbAlc lab results), and diabetes complications (as measured in outpatient visits, emergency room visits, and hospitalizations). Stratifying by type of drug therapy (insulin/combined therapy vs. oral therapy), we will use descriptive analyses, generalized linear mixed models, and proportional hazards models to (1) identify racial differences in self-management practices and diabetes-related health outcomes over time; (2) assess whether African American race is an independent predictor of self-monitoring practice or adherence to drug regimen; and (3) whether there are racial/ethnic differences in the association between self-management and specific clinical endpoints, including glycemic control (HbAlc<8.0) and the incidence of diabetes-related complications over the nine-year study period. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REGULATION OF EXPRESSION OF SECRETED FLT-1 Principal Investigator & Institution: Huckle, William R.; Biomedical Sciences and Pathobiology; Virginia Polytechnic Inst and St Univ 460 Turner Street, Suite 306 Blacksburg, Va 24060 Timing: Fiscal Year 2004; Project Start 01-APR-2004; Project End 31-MAR-2006 Summary: (provided by applicant): Vascular endothelial growth factor (VEGF) is a major mediator of neovascularization in embryonic development and adult vascular homeostasis. VEGF contributes to adaptive angiogenesis in ischemic tissue as well as excessive vessel formation in proliferative vascular pathologies. VEGF and its signaling pathways thus may provide a means of either promoting angiogenesis in vascular insufficiency or inhibiting angiogenesis in diabetic retinopathy or in tumors. Responses to VEGF are mediated by two endothelial cell-surface receptors, Fit-1 and KDR. An RNA processing variant of Fit-1 mRNA produces a secreted form of Fit-1 ("sFIt-1 ") that binds VEGF with high affinity and can inhibit biological responses to VEGF. Previous studies indicate that the ratio of sFIt-l:FIt-1 can vary under physiological conditions, suggesting that molecular mechanisms exist to specifically control the mRNA processing events leading to sFIt-l. We postulate that the relative expression of sFIt-1 and Fit-1 is a significant biological determinant of vascular responsiveness to VEGF. The goals of the proposed research are to identify new experimental systems and biochemical assays to discover the regulatory mechanisms governing sFIt-1 expression. Our specific aims are 1) to identify biological models appropriate for the study of regulated sFIt-1 expression, 2) to identify nuclear factors involved in Fit-1 pre-mRNA processing, and 3) to determine the post-transcriptional mechanism by which protein kinase C activation alters sFIt-1 expression. In Aim 1, we will quantify sFIt-1:Fit-1 expression in cell- or animal-based models of vascular development and adult angiogenesis. Under Aim 2, we will probe the interaction of specific and unknown processing factors with Fit-1 pre-mRNA using cell-free systems. In Aim 3, we will assess the role of altered mRNA stability and pre-mRNA 3rocessing in the induction of sFIt-1
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expression by phorbol ester. These studies will increase our understanding of the mechanisms of both adaptive and therapeutic angiogenesis, and may provide rationale for developing novel pharmacological interventions to modulate sFlt-1 expression and, thereby, VEGF responsiveness. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REGULATION OF HEMANGIOGENESIS BY ADENOVIRAL E4 GENES Principal Investigator & Institution: Rafii, Shahin; Professor of Medicine; Weill Medical College of Cornell Univ New York, Ny 10021 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): Endothelial and hematopoietic cells are ideal targets for gene therapy because are readily accessible to gene therapy vectors via the circulation and play a critical role in the progression of disease processes including inflammation and tumor angiogenesis. Adenoviral (Ad) vectors which could infect quiescent vascular cells provide ideal vectors to introduce genes into vascular endothelium as well as hematopoietic stem and progenitor cells with high efficiency and low toxicity. However, expression of genes by Ad vectors has been hampered by infiltration of inflammatory cells and intravascular activation of neo-intimal cells. Despite numerous studies defining the role of immune response to Ad vectors the exact mechanism whereby Ad vectors modulate activation status of ECs and hematopoietic cells and subsequent inflammatory response is not know. We have shown that introduction of E1-E4+, but not E1-E4-Ad vectors into primary ECs results in profound alteration in the proliferation and inflammatory status of the ECs. Infection of ECs with E4+ Ad vectors result in the generation of unique state where ECs do not proliferate or undergo apoptosis. This state is also associated with the upregulation of inflammatory adhesion molecules including ICAM, VCAM, and CD34. Moreover, E4 mediated activation of ECs enhance transendothelial migration of hematopoietic precursor cells and proinflammatory cells. These data clearly demonstrate that one or a combination of E4 gene products encoded by seven distinct E4 open reading frames (ORFs) regions may play a critical role in modulation of angiogenic and inflammatory potential of ECs. Based on these data, we hypothesize that gene products encoded by the E4 region of Ad vectors pirate the molecular machinery of ECs resulting in transformation of ECs into a unique pro-angiogenic and proinflammatory state. Identification of E4ORF genes that modulate angiogenic and inflammatory potential of ECs hematopoietic cells will facilitate designing strategies to attenuate vascular toxicity associated with Ad vector gene therapy. The mechanism by which E4ORFs gene products modulate angiogenic and inflammatory potential will be investigated through studying the following experiments: 1) Identifying specific E4ORF genes that alone or in combination modulate angiogenic and inflammatory potential of ECs in in vitro and in vivo models. 2) Assess the effect of E4ORFs gene products in the modulation of angiogenic potential of circulating VEGFR2+AC133+endothelial precursor cells (EPCs) and hematopoietic stem and progenitor cells. 3) Define the mechanism(s) whereby E4ORFs modulate the motility and mitogenic potential of ECs and hematopoietic progenitor and stem cells. 4) Define the role of E4ORFs in physiological models of angiogenesis and inflammation. These experiments may culminate in identification of E4ORFs that promote or inhibit angiogenesis, and diminish E4 mediated vascular toxicity. Incorporation of proangiogenic E4ORFs in conjunction with transgenes expressing VEGF, will facilitate developing clinical strategies to enhance collateral formation in ischemic myocardium or limbs. Conversely, E4ORFs with anti-angiogeni properties may be used in clinical
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Diabetic Retinopathy
strategies that are targeted at inhibiting tumor angiogenesis or blocking aberrant angiogenesis in clinical scenarios, such as diabetic retinopathy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REGULATION OF VASCULAR DEVELOPMENT IN THE MOUSE RETINA Principal Investigator & Institution: Ash, John D.; University of Oklahoma Hlth Sciences Ctr Health Sciences Center Oklahoma City, Ok 73126 Timing: Fiscal Year 2002; Project Start 16-SEP-2002; Project End 31-AUG-2007 Summary: Proliferative retinopathies (PRs) are a classification of diseases that include sickle cell retinopathy, diabetic retinopathy, branch vein occlusion retinopathy, and retinopathy of prematurity. These diseases all are characterized by the loss of normal blood vessels in the retina and subsequent uncontrolled growth of abnormal blood vessels in the vitreous of the eye. As in humans, retinal ischemia in mice induces growth of abnormal vessels in the vitreous. In contrast to humans, mice are only transiently affected by the growth of abnormal blood vessels in the vitreous. Within a short period, normal blood vessels will re-grow within the mouse retina and the abnormal vessels in the vitreous will spontaneously resolve. The regrowth of normal retinal vessels provide mice with an endogenous mechanism for long-term protection from proliferative retinopathy. We hypothesize that the rodent retina is competent to promote retinal vascular regrowth through the expression of genes that are essential regulators and effectors of blood vessel growth and stability. Our goal is to identify the molecular regulators and effectors of vascular growth in the mouse retina. We have previously demonstrated that transgenic expression of either activated transforming growth factor 131(TGF-131) or leukemia inhibitory factor (LIF) in the lens alters the environment within the retina so that it is no longer competent for vascular development. Our strategy is to identify the genes that are expressed in wild type retinas which can promote vascular development, but that are not expressed in retinas which have lost the ability to support vascular development. In the current proposal, we will use transgenic mice in which we can induce the expression of TGF-131 (aim 1), or LIF (aim 2) in retinal photoreceptors, so that we can turn off retinal competence for vascular development at ages corresponding to the beginning, to the middle, and to completion of normal retinal vascular development (aims 1 and 2). With these mice, we will test the hypothesis that cytokines reduce growth of vascular endothelial cells or increase vascular degeneration. We will also test the hypothesis that cytokines down-regulate the expression of specific genes that are necessary for retinal vascularization (aim 3). This will allow us to identify genes that are regulators and effectors of retinal vascular development in mice. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: REGULATION OF VEGF MRNA STABILITY BY HYPOXIA Principal Investigator & Institution: Furneaux, Henry M.; Associate Professor; Cell Biology; University of Connecticut Sch of Med/Dnt Bb20, Mc 2806 Farmington, Ct 060302806 Timing: Fiscal Year 2002; Project Start 01-JAN-1999; Project End 31-DEC-2003 Summary: (Adapted from Investigator's Abstract): Vascular endothelial growth factor (VEGF) is an important mediator of angiogenesis in diabetic retinopathy, cancer and coronary heart disease. The expression of VEGF is tightly controlled to the cellular oxygen tension. Previous studies have shown that VEGF mRNA is markedly stabilized under hypoxic conditions. The molecular mechanisms underlying the regulation of
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VEGF mRNA stability are not well understood. In the preliminary results the applicant showed that the stability of VEGF mRNA is controlled by a cis acting element in its 3'UTR. They have also identified a trans acting factor (HuR) that binds to this element and increases the expression of VEGF. In addition, they show that HuR itself is regulated by hypoxia. This proposal will focus on the role of HuR in hypoxic regulation of VEGF mRNA stability. The proposed studies may be important since they could lead to the generation of new drugs that will regulate VEGF expression at the post transcriptional level. The specific aims of the proposal are the following: (1) To determine the fine structure of the HuR/VEGF mRNA complex. To generate mutations in both the mRNA element and HuR and determine their effect on VEGF expression; (2) To design selective inhibitors of HuR/VEGF mRNA complexes; (3) To identify and clone HuR associate proteins that modify its activity; (4) To determine how hypoxia regulates HuR expression; and (5) To determine how HuR stabilizes VEGF mRNA. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REMOTE EXPERT SCREENING FOR DIABETIC RETINOPATHY Principal Investigator & Institution: Meeder, Torre; Eyetel Corporation 15078 Stillfield Pl Centreville, Va 20120 Timing: Fiscal Year 2002; Project Start 30-SEP-1999; Project End 31-MAR-2004 Summary: (provided by applicant): Half of diabetic patients do not visit an ophthalmologist as recommended, resulting in frequent and unnecessary vision loss. The NEI has set as an Healthy People 2010 objective to increase the screening rate for diabetic retinopathy. EyeTel-lmaging and the Wilmer Eye Institute are developing technology to screen diabetic patients during their visits to their primary care physician (PCP). The DigiScope, a low cost, quasi-automatic computerized fundus camera acquires digital stereoscopic fundus images and assesses visual acuity. The data are automatically transferred, via the Internet, to a reading center where expert readers, supervised by retinal specialists, identify patients with retinopathy and refer them to an ophthalmologist. The DigiScope will be provided to PCPs without capital investment on their part and a service fee will be collected from health care providers. The goals of Phase I were exceeded with the successful development of the DigiScope and the results of an independent study. In comparison with the 'gold standard', the DigiScope had a sensitivity of 98.5 percent and a specificity of 92 percent. The goals of phase II are to meet all the specifications for implementation in PCPs offices, develop the reading center and assess the impact on screening rate in different health care environments. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: RENIN ANGIOTENSIN SYSTEM BLOCKAGE-DN (RASS) Principal Investigator & Institution: Mauer, S Michael.; Professor; Pediatrics; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2003; Project Start 16-MAR-1997; Project End 31-MAY-2008 Summary: (provided by applicant): Diabetes nephropathy (DN) is the most important cause of kidney failure. Patients (pts) with Type 1 diabetes mellitus (DM) who develop DN have a markedly increased death rate from kidney failure, coronary artery disease and stroke. Glycemia only partly explains why some pts develop these DM complications. Further, since tight blood sugar control is extremely difficult to maintain, other efforts need to be made to reduce risks of DM complications. Renin-angiotensin system (RAS) inhibitors slow the progress of established DN. The specific aim of this study is to determine whether treatment at the early stages of DM can slow or stop DN
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Diabetic Retinopathy
structural changes. The long-term objective is to prevent DN from developing. Two hundred eight five pts ages 16-59 with 2-29 yrs of Type 1 DM and no renal functional abnormalities have been randomized into a parallel, double-blind, placebo-controlled study involving 3 groups (95 pts/group). Each group receives an angiotensinconverting enzyme inhibitor (ACEI) (enalapril), or an angiotensin II receptor blocker (losartan), or placebo. All pts have their usual DM management. Baseline studies included measures of glomerular filtration rate (GFR), urinary albumin excretion rate (UAE), blood pressure (BP), and a percutaneous renal biopsy. Pts are followed by quarterly measures of BP, HbA1C, UAE, and drug compliance. There are annual measures of GFR and a repeat renal biopsy after 5 yrs in the study. The main endpoint is kidney structural changes over time, especially mesangial fractional volume [Vv(Mes/glom)]. Secondary endpoints will be other DN structural measures and measures of kidney function (UAE, GFR). These studies will determine whether RAS blockage in the early stages of DN can prevent the early kidney structural changes in this important disorder. Ancillary studies will evaluate the effects of treatment group on the development and progression of diabetic retinopathy and will develop predictors of study participants' compliance. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: RETINAL BLOOD FLOW AND MICROTHROMBI IN TYPE 1 DIABETES Principal Investigator & Institution: Lorenzi, Mara; Associate Professor; Schepens Eye Research Institute Boston, Ma 02114 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2005 Summary: (provided by applicant): The greatest likelihood of lessening the threat of diabetic retinopathy is through prevention. Preventative strategies must target pathogenic events that occur early in diabetes, and incorporate methods for monitoring outcomes longitudinally and noninvasively. Previous studies suggest that the formation of platelet-fibrin microthrombi could be an early pathogenic event in the closure and obliteration of diabetic retinal capillaries, and do show reduced retinal blood flow in patients with short diabetes duration and no or minimal retinopathy. The hypothesis to be tested in this project is that the reduced retinal blood flow reflects increased vascular resistance due to microthrombosis, and, operationally, that antiplatelet agents normalize the reduced retinal blood flow. The project aims to (1) confirm that, under basal conditions, retinal blood flow measured with the laser Doppler method in a large group of type 1 diabetic patients with no or minimal retinopathy differs from the flow measured in age- and sex-matched nondiabetic control subjects; (2) determine whether the response of retinal blood flow to low-dose aspirin--expected to be mostly or solely antithrombotic--administered for two months versus placebo, differs between the diabetic and the control group; and (3) determine whether the response of retinal blood flow to low-dose aspirin in type 1 diabetic patients differs from the response to another antiplatelet agent, which is highly selective and acts downstream of the site of aspirin action. The study is designed as a two-arm (diabetic patients and controls), parallelgroup, double-masked, randomized, placebo-controlled trial, involving individuals 1840 years of age with diabetes duration of one to ten years and no or minimal retinopathy. The diabetic subjects will be recruited from the Diabetes Center of the Massachusetts General Hospital. The retinal blood flow measurements will be performed with the Canon Laser Blood Flowmeter, an instrument approved by the FDA and usable with ease in the clinical setting. A finding that early reduction of blood flow reflects the occurrence of microthrombosis in the retina of short-term diabetic patients
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will have identified a pathogenic process for diabetic retinopathy, a surrogate endpoint and a probe for its early detection, and a target for early intervention using benign and clinically available drugs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: RETINAL IMAGE QUALITY IN RETINAL-DISEASED EYES Principal Investigator & Institution: Shahidi, Mahnaz; Associate Professor; Ophthalmology and Visual Scis; University of Illinois at Chicago 1737 West Polk Street Chicago, Il 60612 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2005 Summary: (provided by applicant): The optical properties of the eye and its imperfections limit visual performance, the ability for an individual to view the world, and retinal imaging, the ability for an ophthalmologist to view the retinal tissue. Recent advances in wavefront sensing and adaptive optics technologies have allowed measurement and correction of monochromatic wavefront aberrations in healthy human eyes. However, it is likewise important to investigate disease-related changes in the optics of the eye, since they can significantly contribute to degradation of both visual performance and resolution for retinal imaging. Particularly, there is a need to differentiate between vision loss that results from retinal disease and visual performance that is impaired due to imperfect optics, in order to anticipate optimal outcome for therapies applied to improve neural function of the retina in eyes with imperfect optics, or to foresee consequences of procedures that are targeted to improve the optical property of eyes with diseased retinas. Equally important is a need for high-resolution imaging of the retinal tissue that may be achieved by compensation for ocular aberrations with the use of adaptive optical components and image processing methodologies. Such imaging would allow visualization of fine retinal structures, thus providing for better understanding of retinal pathophysiology and enhanced diagnostic evaluation of retinal diseases. In the current research proposal, our novel technique for optical section retinal imaging will be coupled with wavefront sensing technology. Imaging will be performed in subjects diagnosed with diabetic retinopathy and agerelated macular degeneration and the optical performance of retinal-diseased and healthy eyes will be compared. The relation between ocular aberrations and retinal imaging resolution will be determined. High-resolution retinal imaging will be achieved by compensation for ocular aberrations. Findings from the research study will provide knowledge on the nature and extent of disease-related changes in the optical properties of the eye, that is of value for evaluation of optical factors that contribute to degradation of visuai performance and for achievement of high-resolution retinal imaging in subjects with retinal diseases that are considered the most prevalent causes of blindness. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: RETINAL OXIMETER FOR CLINICAL ASSESSMENTS Principal Investigator & Institution: Beach, James M.; Photon Industries Bldg 9313, Rm 167 Stennis Space Center, Ms 39529 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2004 Summary: (provided by applicant): In this SBIR we propose to develop a retinal vessel oxygen saturation monitoring system for investigational and clinical use. Retinal oximetry has been the subject of intense research and development since Hickam et al published the first photographic means in 1963. Studies of the retinal circulation and oxygen saturation have implicated oxygen status in diseases of the retina, including vein
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occlusion, diabetic retinopathy, glaucoma and optic atrophy. Oximetry studies have shown impairment of retinal blood flow regulation in diabetes and improvement in retinal oxygenation by pan-retinal photocoagulation treatment for proliferative diabetic retinopathy. Recently, studies have used imaging oximetry technique to evaluate side effects of glaucoma medications on retinal oxygenation. Thus, there is growing interest in retinal oximetry for monitoring retinal pathology. We propose here to develop an instrument we call OXYCAM for determining changes in oxygenation from distinct regions of the retina. This ability to detect subtle changes will be important in preventing the blinding complications of retinovascular disease. The long-term objectives of this project are 1) to make available a standardized commercial system for oximetric evaluation of retinal disease in research institutions and clinics and 2) to determine the role of oximetry as a retinal evaluation tool, which will lead to a commercial market for oximetry products. The specific aims of Phase I include 1) development of the dual-wavelength OXYCAM Imaging system for oximetric assessment at different levels of the retinal circulation and 2) validation of the OXYCAM performance in normal subjects. Coverage of retinal vessel networks in single dualwavelength recordings will be achieved with pairs of large-format CCD sensors and a dichroic image splitter. Our longer term aims in Phase II include 1) development of automated vessel tracking and oximetry analysis software, 2) refinement of oximetry technique to improve accuracy and reproducibility in clinical work and 3) multi-site investigations into the role of oximetry in diagnosis, management and treatment of retinal disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: RETINAL OXYGENATION IN DIABETIC RETINOPATHY Principal Investigator & Institution: Berkowitz, Bruce A.; Professor; Anatomy and Cell Biology; Wayne State University 656 W. Kirby Detroit, Mi 48202 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2005 Summary: (provided by applicant): Current treatments for diabetic retinopathy are not entirely successful. We reason that therapies could be more rapidly developed and evaluated than is currently possible if a patient's risk of developing retinopathy could be predicted early in the course of the disease. We have developed a unique functional magnetic resonance imaging (fMRI) technique that measures the change in partial pressure of oxygen (deltaPO2) in the vitreous humor while the subject breathes carbogen (95% O2: 5% CO2). Using this acute retinal "stress" test, we have shown that carbogen breathing in rats and mice at 3-4 months of diabetes (before the appearance of retinal lesions) produces a significantly reduced retinal deltaPO2 compared to normals. A subnormal deltaPO2 is consistent with the presence of hypoxia but it cannot yet be unambiguously interpreted as a measure of hypoxia. In addition, in 3 month diabetic rats, aminoguanidine (AMG) treatment prevented the decrease in retinal deltaPO2. AMG is known to prevent retinal lesion formation in diabetic rats and inhibit the activity of both the inducible form of nitric oxide synthase (iNOS) and protein kinase C (PKC) (among other actions). Hypothesis: Subnormal retinal deltaPO2 in experimental diabetes is correlated with retinal hypoxia (Aim 1), and increased iNOS and PKC activity (Aims 2 and 3) but precedes the appearance of histopathology. Specific Aim 1) To compare retinal PO2 and deltaPO2 before, and at 2 wks, and 3 and 9 months of diabetes in rats. fMRI and a carbogen challenge will be used to measure the retinal deltaPO2. To measure PO2, a perfluorocarbon droplet will be injected into the preretinal vitreous over superior or inferior retina and 19F magnetic resonance spectroscopy performed. Specific Aim 2) To compare the retinal deltaPO2 (at 3 months) and histology
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(at 3 and 15 months) in normal and diabetic rats with and without treatment with a selective iNOS inhibitor (L-NIL (L-N(6)-(1-iminoethyl)lysine)), and in normal, diabetic, and diabetic iNOS knockout mice. Specific Aim 3) To compare the retinal deltaPO2 (at 3 months) and histology (at 3 and 15 months) in normal and diabetic rats with and without treatment with a selective PKC inhibitor (LY333531). In addition, we will compare retinal deltaPO2 in normal mice, transgenic mice that overexpress PKC beta II, diabetic mice, and diabetic PKC beta II-knockout mice. The results of the proposed studies will prove whether or not changes in retinal deltaPO2 correlate with the development of retinal hypoxia or multiple biochemical abnormalities that are associated with diabetic retinopathy but cannot be measured in vivo by existing techniques. The results of these studies could lead to the development of a non-invasive real time method for the early evaluation of diabetic retinopathy and its treatment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: RETINAL VESSEL MEASUREMENT AND CHARACTERIZATION SYSTEM Principal Investigator & Institution: Wilson, Mark P.; Kestrel Corporation 3815 Osuna Ne Albuquerque, Nm 87109 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2004 Summary: (provided by applicant): Retinal microvascular abnormalities are related to many ocular and systemic diseases including diabetic retinopathy, hypertension, stroke, and cerebral micro-vascular diseases. For example generalized arteriolar narrowing and arteriovenous nicking appear to be irreversible long-term markers of hypertension. Findings suggest that retinal photography may be useful for assessing risk stratification and screening for retinal disease in appropriate populations. Highly evolved imaging solutions and computer processing power have opened a door to quantify these abnormalities. A methodology is suggested that is efficient and comprehensive because of computer automation, that is repeatable, free of inter- and intra-reader variability, precise, and consistent with the human analysts' techniques. We propose to develop and validate a system that extracts retinal vessels, classifies their bifurcations and crossings, and quantifies a diameter measurement of the retinal vasculature system. The Auto-Cal system will use advanced morphological and Gaussian filtering techniques to segment the vessel network. Once segmented the crossings and bifurcations will be classified through morphological skeletonization path traversing and pruning algorithms. The vessel diameter is then calculated by fitting the gray level profile to Gaussian parameters that describe a typical vessel. The system will be tested on 50 digital images, which will have their 8 major vessels manually measured with a previously developed computer-aided tool. High statistical correlation with manually derived vessel diameters will determine the success of the process. The specific Phase I aims are to 1) Develop and validate a fully automatic retinal vessel extraction algorithm to segment the arteries and veins from a digital fundus photograph, 2) Develop and validate a vessel bifurcation and crossing recognition algorithm, and 3) Develop and validate a vessel diameter measurement algorithm. In Phase II the Auto-Cal tool will be used in a comparative study to examine 400 pre-proliferative diabetic retinopathy patients. The vessels have been manually measured. These data will be used to validate the system against a large "ground truth" population. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: RISK FACTORS FOR DIABETIC RETINOPATHY IN BLACK AMERICANS Principal Investigator & Institution: Roy, Monique S.; Ophthalmology; Univ of Med/Dent Nj Newark Newark, Nj 07107 Timing: Fiscal Year 2002; Project Start 01-DEC-1992; Project End 31-JUL-2004 Summary: Diabetic retinopathy remains one of the leading causes of blindness in the United States. This disease, and its associated visual impairment, represent a major public health problem particularly for African- American diabetic patients among whom the prevalence of diabetes is high with an increasing incidence. In a previous study (The New Jersey 725), we had assembled a large (n=725) cohort of AfricanAmericans with type 1 diabetes, identified from the New Jersey Hospital Discharge Data files. In that study, we delineated frequency of retinopathy and associated visual impairment (which are high, 64% and 11% respectively) as well as identified (in addition to duration of diabetes) three systemic modifiable risk factors, poor glycemic control, systemic hypertension and renal disease significantly associated with the presence and severity of diabetic retinopathy in this group of patients. The overall goal of the present prospective study is to determine the natural history of diabetic retinopathy in African-Americans with type 1 diabetes and examine the relationship between systemic risk factors listed above and progression of the retinopathy so that therapeutic interventions, targeted at these risk factors, can be appropriate designed. In order to achieve oral overall goal, we plan to obtain follow-up examinations of the patients from the previous study to ascertain () the 6-year incidence and progression of diabetic retinopathy (as graded from standard fundus photographs) and associated incidence of visual impairment and (b) how duration of diabetes and systemic risk factors (glycemic control, blood pressure, and renal disease), as measured at the baseline examination, relate to incidence and progression of diabetic retinopathy. Clinical evaluation of patients will include standardized protocols for ocular examination, fundus photography, structured clinical interview, and blood pressure measurement; laboratory evaluation will include blood assays to evaluate glycemic control, insulin insufficiency, and cholesterol levels, and urine assays to assess diabetic renal disease. Results obtained on incidence and progression of diabetic retinopathy and risk factors for disease progression this population group will provide the data to understand the natural history of the disease in African-Americans with type 1 diabetes. Such data are also essential for planning public health education measures, estimating needs for medical services, and designing community-based intervention studies for the prevention of diabetic complications in this group of Americans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ROLE OF ALK1 TGF-BETA SIGNALNG ON ANGIOGENESIS Principal Investigator & Institution: Oh, S Paul.; Physiology and Functional Genomics; University of Florida Gainesville, Fl 32611 Timing: Fiscal Year 2002; Project Start 01-AUG-2000; Project End 31-JUL-2004 Summary: The establishment and maintenance of a vascular supply are essential for the survival of normal and neoplastic tissues. With the exception of early embryogenesis, new blood vessels are formed from pre-existing vessels by a process called angiogenesis. Angiogenesis occurs during embryonic development, ovarian follicular development and wound healing, and during pathogenesis including solid tumors, diabetic retinopathy and rheumatoid arthritis. The long term goal of my research program is to elucidate biological, molecular and genetic mechanisms underlying regulation of
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angiogenesis during development and post-natal life. Angiogenesis can be separated into two phases: activation and resolution phases. In activation phase the endothelial cells degrade perivascular matrices, migrate and proliferate, while in resolution phase, endothelial cells cease migration and proliferation. Mechanisms controlling these two distinct phases of angiogenesis remain to be understood. Working hypothesis is that activation-resolution phases are determined by a balance between positive and negative regulators: in activation phase, positive regulators predominate, whereas resolution phase is achieved and maintained by the dominance of negative regulators. While a great deal is known about positive regulators (or angiogenic factors), very little is known about the negative regulators involved in the resolution phase of angiogenesis. With the results from our recent molecular genetic studies about the activin receptorlike kinase-1 (ALK1) deficient mice, we hypothesize that ALK-1 may mediate a negative regulator for the angiogenic balance. The specific aims of this proposal is to test this hypothesis using in vivo and in vitro approaches. Results from this proposal would enhance our current understanding on the angiogenic balance. This knowledge can be readily applicable to various vascular pathogenesis including atherosclerosis, retinopathy and hereditary hemorrhagic telangiectasia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ROLE COMPLICATIONS
OF
COMPLEMENT
IN
VASCULAR
DIABETIC
Principal Investigator & Institution: Halperin, Jose A.; None; Harvard University (Medical School) Medical School Campus Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 15-SEP-2002; Project End 31-JUL-2006 Summary: (provided by applicant): Epidemiological studies have established that hyperglycemia is responsible for the micro- and macrovascular disease that characteristically complicates human diabetes. However, the mechanism by which hyperglycemia causes vascular complications is poorly understood, in part because of the known absence of adequate animal models of diabetic complications. Indeed, no single animal model of diabetes reproduces the extensive vascular proliferative complications in the combination and intensity seen in humans. Thus, it appears that neither hyperglycemia itself nor the multiple signals activated by hyperglycemia are sufficient to induce in animals human-like vascular diabetic complications. This implies that there must be one or more genes and/or pathways necessary for the development of the diabetic vascular complications in humans that in animals differ substantially in their sensitivity to hyperglycemia and/or glycation. We have identified that the gene encoding for the complement regulatory membrane protein CD59, which inhibits formation of the membrane attack complex (MAC), is structurally different in humans and animals because hCD59 contains a glycation motif, formed by its H44 residue at approximately 5A angstroms from K41. We have shown that the K41-H44 motif makes hCD59 sensitive to inactivation by glycation, and that the H44 residue is not present in CD59 from other species. We postulate that glycation-inactivation of hCD59 due to its unique H44 residue could represent the elusive link between hyperglycemia and vascular proliferative complications of human diabetes. Consistently, high levels of glycated CD59 are found in diabetic urine, plasma and tissues; and glycated CD59 colocalizes with increased MAC deposition in kidneys, nerves and veins from diabetic subjects. Increased MAC deposition in the target tissues releases growth factors and cytokines that stimulate cell proliferation and induce synthesis of collagen type IV by glomerular mesangial cells. Increased MAC-induced mitogenic signals in diabetic tissues would act synergistically with other hyperglycemia-induced pathways causing
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vascular proliferative diabetic complications. In this application, we propose to use available mCd59KO and transgenic hCD59 mice to further investigate the causative role of glycation-inactivation of hCD59 in the pathogenesis of vascular proliferative complications of diabetes. We will phenotype diabetic mCd59KO, mCd59KO/hCD59WT, and mCd59KO/hCD59GIn44 variant transgenic mice for the development of human diabetic-like vascular disease, Mice will be made diabetic by injection of streptozotocin, and phenotyped by histopathology and parameters of retinal hemodynamic and renal function. We expect that in mCd59KO and in mCd59KO/hCD59WT mice, hyperglycemia will trigger a vascular proliferative response comparable to that seen in human diabetes. Instead, the hCD59GIn44 variant (resistant to glycation-inactivation) should protect mCd59KO from hyperglycemiainduced proliferative disease. We expect that these experiments will provide: 1) clear evidence for the role of glycation-inactivation of hCD59 in the pathogenesis of the proliferative vascular complications of diabetes; 2) needed animal models to study mechanism, therapy and prevention of diabetic complications; and 3) strong evidence to support future studies on complement and diabetes in humans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: RUNX SPECIFIC ANGIOGENESIS INHIBITORS Principal Investigator & Institution: Passaniti, Antonino; Pathology; University of Maryland Balt Prof School Baltimore, Md 21201 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2004 Summary: (provided by applicant): Recruitment of new blood vessels (angiogenesis) is required for tumor growth and metastasis. Therefore, the development of angiogenesis inhibitors represents a new approach that may increase the effectiveness of existing cancer treatments. Runt family genes (Runx1,2,3) are transcription factors that playa key role in vascular development including endothelial cell (EC) migration and stem cell recruitment to promote angiogenesis. Runx DNA binding is enhanced by association with the product of the Cbf gene which forms a trimeric DNA binding complex whose 3-dimensional (3D) structure has recently been determined. Computer-aided rational drug design (CADD) can be used to identify chemical compounds with the potential to become therapeutic agents. CADD database searching involves screening of a 3D chemical database to select small molecules that "fit" in the binding site of interest on the target biomolecule. The identified small molecules are then obtained and subjected to experimental assays to select those with the appropriate biological activity. Use of a database of commercially available compounds avoids the need for chemical synthesis, thereby facilitating the identification of active compounds. Our hypothesis is that specific inhibition of Runx-mediated transcriptional activation will inhibit EC migration and angiogenesis. Our goals are to use CADD, in combination with the available 3D structure of Runt to identify compounds with a high potential to bind selectively to Runt. Both the DNA and Cbf binding regions of Runt will be individually targeted. The selected compounds will be obtained and subjected to experimental testing using assays to identify compounds with the desired Runt-binding activities to verify that they are Runt-specific antagonists. An EC migration assay will then be used to screen candidate compounds for biological activity. These approaches are one of the first attempts to inhibit angiogenesis via transcriptional targeting. Since inhibiting Runx transcriptional activity should reduce angiogenesis, the growth of both hematopoietic and solid tumors that depend on a blood supply for survival and growth will be inhibited. The lead compounds developed from this application could also find utility in non-cancer
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situations, such as macular degeneration, atherosclerosis, or diabetic retinopathy, where uncontrolled angiogenesis is responsible for the pathology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: STATISTICAL CLUSTER DATA
METHODS
FOR
OPHTHALMOLOGIC
AND
Principal Investigator & Institution: Rosner, Bernard A.; Professor; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 01-AUG-1998; Project End 31-JUL-2005 Summary: (provided by applicant): Correlated data are the norm in ophthalmologic data, due to correlated response for paired eyes. An abundance of methods are now available that enhance standard models by incorporating clustering effects (Rosner, 1984; Liang and Zeger, 1986). These methods are limited usually to either normally distributed or binary outcomes. However, many scales used in ophthalmology are continuous, but non-normally distributed (e.g. visual field area). Other scales are ordinal and non-normally distributed, but are sometimes treated as normally distributed as well (e.g. diabetic retinopathy grade). Nonparametric methods are a natural approach for such scales. In this proposal, we propose a model for incorporating clustering effects for ranked data and use this model to extend tests such as the Mann-Whitney U test for the clustered data situation. In addition, we propose extensions to allow for tied values and to adjust for other covariate effects. Another issue in ophthalmologic data is that some endpoints are composite in nature (e.g. nuclear cataract, cortical cataract, PSC cataract, control). An interesting issue is that the risk factor profile for some risk factors may be different for different types of cataract, while for other risk factors it may be the same. (Marshall & Chisholm, 1985). We propose to use a flexible type of polytomous regression model in this setting and to enhance it by considering matched designs as well as outcome categories that are not mutually exclusive. Furthermore, we propose to develop a user-friendly software package to easily fit such models including use of stepwise regression strategies. A third area of interest is the use of correlated data methods in a small sample setting. Most previous methods developed have good asymptotic properties but depend on at least a moderately sized sample for their validity.We propose to extend existing methods of exact inference by incorporating clustering effects and making these methods available by exportable software. Finally, the area under the ROC curve is frequently used as a measure of goodness-of-fit for logistic regression models. However, its use is problematic if separate logistic models are fit for the right and left eyes of an individual in ophthalmologic studies. We propose to extend traditional ROC curve methods (Hanley and McNeil, 1982) to the clustered data situation where outcome on fellow eyes may be either concordant (bilateral cases) or discordant (unilateral cases). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: STRUCTURE/FUNCTION OF CONNECTIVE TISSUE GROWTH FACTOR Principal Investigator & Institution: Grotendorst, Gary R.; Professor; Cell Biology and Anatomy; University of Miami-Medical Box 248293 Coral Gables, Fl 33124 Timing: Fiscal Year 2002; Project Start 01-SEP-2001; Project End 31-AUG-2005 Summary: Fibrotic disorders represent the largest segment of human disease for the populations of North America, Europe and Japan. These disorders are characterized by an overproduction of connective tissue (primarily collagen) and are widely recognized
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Diabetic Retinopathy
to be initiated in response to some type of injury which leads to the chronic inflammation and subsequent overproduction of growth factors that encourage the formation of connective tissue. There are no current therapies short of transplant or grafts which are effective to control the progression of any fibrotic disorder. Intensive studies over the last 25 years now suggest that a common mechanism may underlie many of these disorders. Thus, an advancement in our understanding of the cellular and molecular control mechanisms which regulate this process could have a significant impact on a wide range of human diseases, including atherosclerosis, pulmonary fibrosis, glomerulosclerosis, arthritis, glaucoma, diabetic retinopathy and others. One common growth factor which has been demonstrated to be overproduced in all fibrotic disorders examined to date is TGFb, which is believed to be an initiator of the connective tissue formation in these disorders. During the course of our studies on mechanisms whereby TGFb stimulates connective tissue formation, we discovered another growth factor, Connective Tissue Growth Factor (CTG F). CTGF synthesis selectively induced in mesenchymal cells by TGFb. We have found that agents which block CTGF synthesis or action are effective inhibitors of TGFb induced fibroblastic cell proliferation and collagen synthesis. This suggests that CTGF may be an important therapeutic target for the control of connective tissue formation in fibrotic disorders. Recently, we have determined that the individual domains of CTGF are responsible for signaling either the mitogenic activity (C-terminal domain of CTGF) or matrigenic activity (N-terminal domain). Our data also indicate that CTGF has an absolute requirement for the presence of EGF for mitogenic and IGF-2 for matrigenic activity. The current project will determine in a more detailed manner the role of the CTGF, CTG F, lGF and EGF receptors and the roles of EGF and IGF factor for signaling the mitogenic and matrigenic actions induced by TGFb in fibroblastic cells. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: STUDY CHAIR CORE CENTER:DME CLINICAL RESEARCH NETWORK Principal Investigator & Institution: Aiello, Lloyd P.; Associate Professor; Joslin Diabetes Center Boston, Ma 02215 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-JAN-2006 Summary: (provided by applicant): Diabetic macular edema (DME) remains a leading cause of visual loss in patients with diabetes mellitus. Increased understanding of this condition has prompted investigations of novel therapies for the treatment of DME, several of which are nearing clinical trial evaluation. Although therapeutic methodology may vary widely, the basic components requiring careful consideration in the design, implementation and analyses of high quality clinical trials are often similar. Furthermore, study sites with particular retinopathy trial expertise and experience are an excellent resource for a variety of such trials. The goal of this proposal is to establish a clinical trial network to evaluate new treatments for diabetic macular edema that may be more effective, better tolerated, or more readily administered than the present standard of laser photocoagulation. This initiative will utilize a framework specifically designed to provide accelerated clinical research, standardized treatment protocols, leveraged recruitment power of multiple centers and optimal resource utilization. These benefits will be realized through the advantages of a dedicated disease approach, coordinated administration, knowledgeable leadership, experienced clinical centers and efficient (re)utilization of components common to multiple trials. This application for the Study Chair core of the Diabetic Macular Edema Clinical Research Network exploits the PI's unique qualifications to serve as Study Chair for this network. Over the past
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decade, the PI has achieved international recognition through participation in clinical and research evaluation of diabetic retinopathy and DME. The PI is currently the Study Chair of 3 ongoing, multicenter (100 sites), randomized, clinical trials evaluating new therapies for diabetic retinopathy and DME. These studies are run under the PI's guidance using a nearly identical administrative and clinical framework as that presented in this proposal. Thus, the PI has unique direct experience in protocol development and operational management required within such a Network. Additionally, the Joslin Diabetes Center provides exceptional support for trial networks with its close integration of all diabetes-associated health care professionals and its basic and clinical research and technology prowess. This proposal details the manner in which the specific goals of the network will be fostered under the guidance of the Study Chair. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SUPPLEMENTAL OXYGEN FOR HYPOXIA-RELATED RETINAL DESEASES Principal Investigator & Institution: Nguyen, Quan D.; Medicine; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 01-SEP-2001; Project End 31-AUG-2006 Summary: (Candidate's Abstract) Hypoxia is thought to play a role in the pathogenesis of several ocular diseases. It is Clear that hypoxia is the driving force behind the development of retinal neovascularization (NV) in patients with ischemic retinopathies, including diabetic retinopathy and central and branch retinal vein occlusions. Macular edema is another major cause of decreased vision in ischemic retinopathies and it is suspected, but not yet proven that hypoxia plays a critical role. Likewise, it is suspected, but not yet proven, that hypoxia contributes to the development of choroidal neovascularization (CNV) in patients with age-related macular degeneration (AMD). Supplemental inspired oxygen provides a means to enhance oxygenation in the retina and choroid. We propose to use supplemental inspired oxygen to test several hypotheses related to the role of hypoxia in ocular NV and macular edema. The following experimental questions will be addressed. (1) Does supplemental inspired oxygen cause regression or slow progression of retinal NV that is not high risk in patients with diabetic retinopathy? (2) Does supplemental oxygen cause improvement in macular edema in patients with ischemic retinopathy? (3) Does supplemental oxygen cause stabilization or improvement in AMD patients with predominantly occult subfoveal CNV? (4) Does supplemental oxygen decrease recurrent CNV in AMD patients with predominantly classic CNV treated with photodynamic therapy? The answers to these questions will provide important insights into the pathogenesis of retinal diseases that could lead to the development of new treatments. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: TESTS DISEASES&ADAPTION
OF
MODELS
OF
RETINAL/OPTIC
NERVE
Principal Investigator & Institution: Hood, Donald C.; Professor; Psychology; Columbia Univ New York Morningside 1210 Amsterdam Ave, Mc 2205 New York, Ny 10027 Timing: Fiscal Year 2002; Project Start 01-AUG-1977; Project End 31-JUL-2005 Summary: A major long-term objective is to develop techniques for localizing the sites, and identifying the mechanisms of diseases of the retina and optic nerve. The multifocal electroretinogram (mERG) and visual evoked potential (mVEP) techniques are relatively
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new ways for measuring the physiological activity of local retinal and cortical activity. By studying the mERGs from patients with a variety of retinal/optic nerve problems we aim to develop a conceptual framework for relating changes in the mERG to sites and mechanisms of damage (aim 1a). In addition, some retinal diseases affect retinal mechanisms of adaptation and studies are designed to understand these changes. The mVEP technique is less developed and studies are proposed to improve this technology. These include the development of a method for measuring and specifying the strength of the signal in the mVEP response (aim 1b). Specific studies are proposed to understand the contribution of cone pathways to the mVEP, to assess repeat reliability, to optimize recording techniques, and to develop norms. The second long-term objective is to improve our understanding of the sites and mechanisms of particular diseases of the retina/optic nerve through studies employing behavioral (e.g. visual fields), structural (e.g. nerve fiber layer analysis) and electrophysiological techniques (e.g. mERG and mVEP). As part of aim 2, the mERG and visual field measures will be employed to better understand retinal damage in patients with retinitis pigmentosa and diabetic retinopathy and to assess possible damage following retinal surgery for macular holes and macular pucker. In addition, the sites and mechanisms of glaucomatous damage will be studied. These studies include a comparison of structural and functional measures to better understand the mechanism(s) of damage, an attempt to detect early damage, an assessment of the effect of acute decreases in intraocular pressure, and an assessment of whether there are selective deficits in the cone pathways. Finally, patients with acute optic neuritis will be followed with behavioral and mVEP techniques. An attempt will be made to understand the recovery o vision following optic neuritis (ON). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: THE DEVELOPNENT
ROLE
OF
ARNT
IN
VASCULAR
AND
CARDIAC
Principal Investigator & Institution: Ramirez-Bergeron, Diana L.; Anatomy; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2003; Project Start 09-JUN-2003; Project End 31-MAY-2008 Summary: (provided by applicant): The objective of this K01 award is to provide intensive mentoring and research training to the minority principal investigator that will allow for an effective transition into an independent academic researcher. The candidate will receive scientific and career mentorship from well established, highly motivational sponsors and advisory committee members. In the past, the investigator has focused on hematopoietic development. The proposed research will redirect her research to acquisiton of new skills in the areas of cardiovascular development and hypoxic biology. The proposal is based on work from Dr. Simon's laboratory encompassing work in hematopoiesis and vasculogenesis. Mutations in various subunits of the Hypoxia Inducible Factor (HIF) family, an important hypoxic transcriptional mediator, have contributed to the understanding the role 02 tension plays during early embryonic development. Abrogation of the Arnt subunit of the HIF heterodimer resulted in embryonic lethality by 10.5 days postcoitum (dpc) with yolk sac, placental, cardiac, and vascular defects. The goal of this proposal is to characterize the role of 02 in cardiovascular development, particularly on endothelial cells. The specific aims are to 1) determine how hypoxia influences endothelial behavior, 2) examine the hematopoietic and angiogenic potential of intraembryonic tissues of Amt -/- mice, and 3) determine the effect of hypoxia in heart development. Accomplishing these specific aims will provide an understanding of hypoxic signals in mediating biological responses required for the growth and differentiation of the cardiovascular system. Furthermore, the
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examination of the cellular and molecular responses to hypoxia will provide important insights into various disease states, including tumor growth, diabetic retinopathy, preeclampsia, wound healing, and ischemia. Additionally, the detailed studies of this proposal and the senior guidance of the faculty committee will assist in commanding the investigator into a leader in the field of cardiovascular biology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: INHIBITOR
THERAPEUTIC
POTENTIAL
OF
A
NOVEL
ANGIOGENIC
Principal Investigator & Institution: Ryan, James C.; Genekeys, Llc 1067 Blue Marlin Dr Charleston, Sc 29412 Timing: Fiscal Year 2003; Project Start 01-MAY-2003; Project End 31-OCT-2003 Summary: (provided by applicant): Retinal neovascularization and vascular leakage are common causes leading to retinal damage in diabetic retinopathy. Currently, there is no satisfactory treatment to stop neovascularization or to reduce vascular permeability in diabetic retinopathy, which is a leading cause of blindness in the US and the industrialized countries. Accumulating evidence suggests that decreased levels of endogenous angiogenic inhibitor (e.g. pigment epithelium-derived factor, PEDF) in the retina and vitreous as well as increased angiogenic stimulators (e.g. vascular endothelial growth factor, VEGF) play a critical role in the development of retinal neovascularization. Therefore, delivery of angiogenic inhibitors into the eye is believed to be a promising therapy for retinal neovascularization. Kallikrein-binding protein (KBP, or kallistatin) is a specific inhibitor of tissue kallikrein. It belongs to the family of serine proteinase inhibitors (serpin) and has significant sequence homology with the potent angiogenic inhibitor, PEDF. Recently, we have found that KBP specifically inhibits the proliferation of primary endothelial cells and down-regulates VEGF expression. This vascular activity is independent of its interactions with tissue kallikrein. Moreover, KBP levels are decreased in the vitreous of patients with proliferative diabetic retinopathy and in the retina of a diabetic animal model. Our hypothesis is that KBP is a potent angiogenic inhibitor, which inhibits retinal neovascularization and reduces vascular leakage. The principal objective of this Phase I project is to determine the efficacy of KBP as an antiangiogenic agent in vivo. This Phase I project will determine if KBP can inhibit retinal neovascularization in an animal model of oxygeninduced retinopathy. Recombinant KBP will be injected intravitreally into newborn rats with oxygen-induced retinopathy. Its effect on retinal neovascularization will be evaluated by fluorescein angiography and quantification of pre-retinal vascular cells. This project will also determine if KBP can reverse vascular hyper-permeability in the retina of diabetic animals. VEGF is a major factor responsible for hyper-permeability in diabetic retinopathy. Given that KBP decreases VEGF levels, it may reverse hyperpermeability. This study will use oxygen-induced retinopathy and streptozotocin (STZ)induced diabetic rats as models. The effect of KBP injection on vascular permeability will be evaluated by the Evans Blue leakage method. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: THICKENING RETINOPATHY
OF BASEMENT MEMBRANE IN DIABETIC
Principal Investigator & Institution: Roy, Sayon; Ophthalmology; Boston University Medical Campus 715 Albany St, 560 Boston, Ma 02118 Timing: Fiscal Year 2004; Project Start 01-JAN-2004; Project End 31-DEC-2007
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Summary: (provided by applicant): Vascular basement membrane thickening is a prominent and characteristic lesion of diabetic retinopathy. The goal of this project is to test the hypothesis that the thickened vascular basement membrane (BM) occurring in diabetes plays a role in the development and progression of serious structural and functional abnormalities of diabetic retinopathy. The hypothesis is based on recent findings that human retinal vessels manifest alterations that can be induced by the thickened BMs and, in turn, can compromise the integrity of the vessels' inner lining. In retinal capillary cells of diabetic individuals there is increased production of the BM proteins, fibronectin (FN), collagen IV (coil IV), and laminin (LM). Antisense oligonucleotides developed in our laboratory specifically down-regulate overexpression of the three BM components in microvascular endothelial cells grown in high glucose medium. Furthermore, inhibition of FN overexpression with the FN antisense oligonucleotide partially prevented the development of thickened vascular BM in retinal capillaries of galactose-fed rats, an animal model of diabetic retinopathy, with beneficial consequences to histological lesions. To completely prevent or reverse vascular BM thickening, and regulate functional abnormalities, the development of a more effective antisense strategy is necessary. Having identified antisense oligos that independently down-regulate FN, coil IV or LM expression in retinal vascular cells, in the proposed studies we plan to: (1) Establish whether combined antisense oligo approach prevents vascular BM thickening in rat retinas, and affects FN, coil IV, LM turnover in matrix. (2) Determine if downregulation of the specific BM genes reverses BM thickening, reduces vascular lesions, and affects cellular processes in retinas of diabetic rats. (3) Determine whether high glucose-induced or diabetes-induced altered expression of BM components plays a role in vascular permeability. FN, coil IV, and LM protein level will be monitored by Western blot analysis and immunohistochemistry; RNA level will be analyzed by RT-PCR. Retinal capillary BM width will be measured by morphometric analysis of electron micrographs. Vascular lesions will be assessed from retinal trypsin digests and image analysis. Findings from this project will establish or exclude a pathogenetic link between a discrete biosynthetic abnormality and the development of structural and functional lesions of diabetic retinopathy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: THREE-DIMENSIONAL OCT FOR DETECTION OF MACULAR EDEMA Principal Investigator & Institution: Zhou, Qienyuan; Laser Diagnostic Technologies, Inc. 10864 Thornmint Rd San Diego, Ca 92127 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-MAR-2003 Summary: (provided by applicant): Macular edema(ME) is a common cause of significant visual loss in a wide variety of ocular condition, including age-related macular degeneration (AMD) and diabetic retinopathy (DR). The early detection and classification of ME is of special importance in DR, since the optimum treatment depends on position, type, and extension of the ME. Our long term goal is to develop a clinically useful tool to map macula thickness, to screen for clinically significant macular edema, and to provide high resolution images of retinal cross-sections at any arbitrary retinal locations. In the proposed technique, the rapid transverse imaging mode of the scanning laser ophthalmoscope (SLO) will be combined with high depth resolution and sectioning capability of the optical coherence tomography (OCT). This instrument will be able to image the retina in three dimensions, delineate ME boundaries, and quantify ME volume. During Phase l of this study, we will focus our effort on proof of feasibility. We will modify a breadboard system based on a Topographic Scanning System
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TopSS(Laser Diagnostic Technologies, Inc.) perform in vivo measurements on a few normal subjects and a few ME patients, develop 3-D image processing software, and identify potential problems and improvements for Phase II work. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HOMEOSTASIS
THROMBOSPONDIN-1
AND
RETININAL
VASCULAR
Principal Investigator & Institution: Sheibani, Nader; Assistant Professor; Ophthalmology and Visual Sci; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2006 Summary: (provided by applicant): Diabetes predominantly affects the microvascular circulation of the retina resulting in a range of structural changes that are unique to this tissue. These changes include an early persistent loss of pericytes from retinal microvessels, thickening of the basement membrane, followed by hyperproliferation of endothelial cells (ECs) and abnormal vascularization of the retina, which ultimately results in blindness. Retinal vascularization is normally restricted to the superficial and deep layers of the retina. Other ocular sites such as cornea, lens, and vitreous are normally vascular free. It has been hypothesized that a negative regulator of angiogenesis is responsible for these vascular restrictions. We have recently demonstrated that thrombospondin-1 (TSP1), a potent natural inhibitor of angiogenesis, is present at ocular avascular sites and TSPt expression is dramatically down regulated with diabetes. Our hypothesis is that TSP1 is an important modulator of retinal vascular homeostasis whose alterations under pathological conditions such as diabetes and/or ischemia results in retinal neovascularization. The studies proposed here will investigate the role of TSP1 in retinal vascular development and ischemia-induced neovascularization. We will examine the expression of TSP1 in the retina and retinal capillaries during development and determine whether its expression is altered during oxygen-induced ischemic retinopathy. We will compare development of retinal vasculature and their total area in the retina of normal, TSP1 deficient, and TSP1 overexpressing transgenic mice. We will determine whether lack or over-expression of TSP1 influences retinal vascular development and neovascularization in response to hypoxia. Identification of TSP1 as a modulator of ocular vascularization and the study of its mechanisms of action in retinal vascular cells will provide insight into the defects that contribute to retinal neovascularization. This knowledge will provide the rationale for development of new therapeutic approaches for the prevention and/or treatment of ocular diseases with a neovascular component. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TRANSCLERAL DELIVERY OF DRUGS FROM A COLLAGEN SYSTEM Principal Investigator & Institution: Devore, Dale P.; Xium, Llc 55 Beach St, #8 Westerly, Ri 02891 Timing: Fiscal Year 2004; Project Start 01-JUN-2004; Project End 31-MAY-2005 Summary: (provided by applicant) The overall objective of this project is to develop an injectable or implantable matrix system to provide sustained delivery of therapeutic drugs to the posterior chamber of the eye for treatment of macular degeneration, diabetic retinopathy and other ocular diseases. More effective methods of drug delivery to the posterior segment of the eye are needed for treatment of posterior segment
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Diabetic Retinopathy
disease. Current ocular drug delivery systems primarily include topical drops, subconjunctival and peribulbar injections, oral administration, intravitreal injections and implants. Each of these delivery routes has significant limitations for posterior drug delivery. Localized drug delivery would be a great advantage in treating posterior segment disease where systemic side effects can be avoided. The sclera of the eye has been found to be permeable to a wide variety of compounds and may be a possible route for local drug delivery. The objectives of the Phase I project are to formulate collagen-based matrices that can be injected or implanted beneath the conjunctiva and to measure the in vitro human scleral permeability of several drugs including dexamethasone, methotrexate, and vancomycin delivered in these systems. The specific aims are to formulate injectable in situ polymerizing collagen solutions and solid collagen matrices containing fluorescein-labeled drugs and to measure the transcleral diffusion of the target drugs using a specially designed perfusion chamber at Emory University. Injectable, in situ polymerizable collagen will be prepared from animal hide as described in U.S. Patent 5,492,135. Solid collagen will be prepared from chemically derivatized collagen by exposing the derivatized collagen to ultraviolet light. Both preparations will be dosed with fluorescein-labeled drugs. Diffusion through human sclera will be measured in the in vitro perfusion chamber (Emory University). Results will be analyzed to determine the most effective matrix system for sustained drug delivery. This system will then be used in Phase II studies in animal models. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: VEGF EXPRESSION AND ER STRESS IN DIABETIC RETINOPATHY Principal Investigator & Institution: Roybal, Christopher N.; Biochem and Molecular Biology; University of New Mexico Albuquerque Controller's Office Albuquerque, Nm 87131 Timing: Fiscal Year 2002; Project Start 27-MAR-2003; Project End 31-AUG-2005 Summary: (provided by applicant): Our goal is to determine how VEGF translation and transcription is affected by ER-stress and if this mechanism plays a role in experimental retinophathy. Recent publications have shown a correlation between ER-stress and increased levels of VEGF mRNA and protein. Protein synthesis attenuation occurs during ER-stress and has prompted us to examine the role of a proposed internal ribosome entry site (IRES), located in the 5' UTR, in the translation initiation of VEGF synthesis. The role of ER-stress on angiogenesis will be further explored using an in vitro diabetic retinopathy model. The Streptozotocin (STZ) and retinopathy of prematurity (ROP) diabetic rat models are the identified models in which these studies will take place. By confirming or disproving the role of ER-stress on angiogenesis we will develop a greater understanding of vascular associated complications seen in diabetes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: VISION DISABILITIES IN LOW VISION Principal Investigator & Institution: Massof, Robert W.; Professor; Ophthalmology; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 01-AUG-1999; Project End 31-JUL-2003 Summary: (Adapted from the Investigator's Abstract) The proposed research has the goal of developing and validating interval psychometric scales of visual function limitations and vision disabilities. These interval scales will be developed using Rasch probablistic measurement models applied to ordinal patient rating responses to
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individual questions. Once developed and validated, these scales will be independent of the particular assessment used, as long as the instrument is calibrated to the scale. The significance of the proposed research is that it will provide a means of estimating measurements of latent functional ability variables for individual patients with visual impairments. In the future, these measurements can be used for parametric studies, epidemiological studies, and clinical outcome studies. The proposed research will identify the number and nature of functional ability scales. It will determine the dependence of those scales on the diagnosis of visual system disorder, the type of visual impairment, the existence of co-morbidities, and the patient's history of rehabilitation. Existing visual function instruments (NEI-VFQ, VF-14, ADVS, and VAQ) and two general function instrument's individual items will be evaluated with respect to scales. To estimate the scales, a large set of specific cognitive and motor activities (e.g., writing a check) will be classified according to functional domain (reading, fine and gross visual-motor, visual information processing [e.g., recognition, localization, orientation], or mobility). In telephone interviews, low vision patients will be asked to rate the difficulty of performing each activity. Rasch analysis will be used to test the hypothesis that there is a global functional ability scale and to test the validity of the a priori visual function domains. Principal component analysis of response residuals will be used to evaluate the dimensionality of visual function limitations. Patients also will be asked to rate the difficulty of achieving specific activity goals (e.g., cook a meal, manage personal finances) and Rasch analysis will be used to estimate a vision disability scale. Item ordering and item intervals on the scales and scale validity will be compared across diagnostic groups (AMD, glaucoma, diabetic retinopathy, RP, CVA, and anterior segment disorders) and for different types of visual impairments (e.g., acuity loss and contracted visual fields). Person measures of functional ability will be evaluated as a function of severity of visual impairments (visual acuity, contrast sensitivity, visual fields, dark adaptation, color vision). Determining if the NEI-VFQ, VF-14, ADVS, VAQ, SF-36, and SIP can be calibrated to common scales will test the hypothesis that there is a common functional ability variable(s). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: VISUAL IMPAIRMENT, TREATMENT, AND EFFECTS ON THE ELDERLY Principal Investigator & Institution: Sloan, Frank A.; J. Alexander Mcmahon Professor; Ctr/Hlth Policy Law & Mgmt; Duke University Durham, Nc 27710 Timing: Fiscal Year 2002; Project Start 15-APR-2001; Project End 31-MAR-2005 Summary: This four-year study has four major objectives. (1) For elderly persons with diabetes mellitus diabetic retinopathy, glaucoma, and macular degeneration -- diseases that can cause serious impairments to vision and blindness -- we will analyze determinants of utilization of eye care services, and whether or not Medicare beneficiaries with diabetes/diabetic retinopathy and glaucoma receive care in accordance with minimal process of eye care standards. Such standards have been disseminated as guidelines by professional organizations. In this phase, we will address these issues. How do data on patient self-report of diagnosis compare with those obtained from physicians' diagnoses? What proportions of persons with the study diseases receive care at least at the minimum level of guidelines? Holding many factors constant, are there racial differences in treatments for these diseases? (2) We will study the longitudinal course of these diseases, measured in terms of visual and general functional status -- physical, cognitive -- and in terms of placement in a nursing home, and survival. We will analyze effects of care on changes in vision and the other outcome
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measures. Our data are unique both in terms of the length of time over which patients are followed and in the range of health outcome monitored. (3) We will assess the impact of diabetes, glaucoma, and macular degeneration on total Medicare and Medicaid program cost and on costs privately incurred. Program cost will include cost of vision and non-vision services. In our framework, program cost and patient adherence to guidelines will be jointly determined. (4) We will replicate the analysis of the first 2 objectives for complications of diabetes other than for eyes. We will also specify and estimate a dynamic model of utilization of Medicare-covered services by persons with diabetes -- both vision and nonvision care. The main database will be the National Long-Term Care Survey (NLTCS) for 1982-2001, merged with Medicare claims data for 1982-2001. Eleven papers are planned. 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 “diabetic retinopathy” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for diabetic retinopathy in the PubMed Central database: •
Prevention of leukostasis and vascular leakage in streptozotocin-induced diabetic retinopathy via intercellular adhesion molecule-1 inhibition. by Miyamoto K, Khosrof S, Bursell SE, Rohan R, Murata T, Clermont AC, Aiello LP, Ogura Y, Adamis AP.; 1999 Sep 14; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=17969
•
Screening for diabetic retinopathy in James Bay, Ontario: a cost-effectiveness analysis. by Maberley D, Walker H, Koushik A, Cruess A.; 2003 Jan 21; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=140424
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 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. 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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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 diabetic retinopathy, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “diabetic retinopathy” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for diabetic retinopathy (hyperlinks lead to article summaries): •
A Bayesian analysis of the 4-year follow-up data of the Wisconsin epidemiologic study of diabetic retinopathy. Author(s): Angers JF, Biswas A. Source: Statistics in Medicine. 2004 February 28; 23(4): 601-15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14755392
•
A case of progression of diabetic retinopathy during pregnancy. Author(s): Agardh E. Source: Acta Ophthalmologica Scandinavica. 2002 October; 80(5): 524-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12390165
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A comparative study of panretinal photocoagulation and vitrectomy for advanced diabetic retinopathy. Author(s): Brown CD. Source: Military Medicine. 2003 July; 168(7): 553-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12901466
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A computerized method of visual acuity testing: adaptation of the early treatment of diabetic retinopathy study testing protocol. Author(s): Beck RW, Moke PS, Turpin AH, Ferris FL 3rd, SanGiovanni JP, Johnson CA, Birch EE, Chandler DL, Cox TA, Blair RC, Kraker RT. Source: American Journal of Ophthalmology. 2003 February; 135(2): 194-205. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12566024
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A contribution of image processing to the diagnosis of diabetic retinopathy--detection of exudates in color fundus images of the human retina. Author(s): Walter T, Klein JC, Massin P, Erginay A. Source: Ieee Transactions on Medical Imaging. 2002 October; 21(10): 1236-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12585705
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A hemochromatosis-causing mutation C282Y is a risk factor for proliferative diabetic retinopathy in Caucasians with type 2 diabetes. Author(s): Peterlin B, Globocnik Petrovic M, Makuc J, Hawlina M, Petrovic D. Source: Journal of Human Genetics. 2003; 48(12): 646-9. Epub 2003 November 15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14618419
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A new view of diabetic retinopathy: a neurodegenerative disease of the eye. Author(s): Barber AJ. Source: Progress in Neuro-Psychopharmacology & Biological Psychiatry. 2003 April; 27(2): 283-90. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12657367
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A simplified diabetic retinopathy scale. Author(s): Chew EY. Source: Ophthalmology. 2003 September; 110(9): 1675-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=13129860
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Aggravation of proliferative diabetic retinopathy after laser in situ keratomileusis. Author(s): Ghanbari H, Ahmadieh H. Source: Journal of Cataract and Refractive Surgery. 2003 November; 29(11): 2232-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14670438
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Alterations of fatty acid composition of erythrocyte membrane in type 2 diabetes patients with diabetic retinopathy. Author(s): Kulacoglu DN, Kocer I, Kurtul N, Keles S, Baykal O. Source: Japanese Journal of Ophthalmology. 2003 November-December; 47(6): 551-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14636844
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Ambulatory photographic screening for diabetic retinopathy in nursing homes. Author(s): Anderson S, Broadbent DM, Swain JY, Vora JP, Harding SP. Source: Eye (London, England). 2003 August; 17(6): 711-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12928682
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Aqueous flare and macular edema in eyes with diabetic retinopathy. Author(s): Jandrasits K, Krepler K, Wedrich A. Source: Ophthalmologica. Journal International D'ophtalmologie. International Journal of Ophthalmology. Zeitschrift Fur Augenheilkunde. 2003 January-February; 217(1): 4952. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12566873
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Aspirin for diabetic retinopathy. Author(s): Kohner EM. Source: Bmj (Clinical Research Ed.). 2003 November 8; 327(7423): 1060-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14604902
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Assessing progression and efficacy of treatment for diabetic retinopathy following the proliferative pathway to blindness: implication for diabetic retinopathy screening in Taiwan. Author(s): Liu WJ, Lee LT, Yen MF, Tung TH, Williams R, Duffy SW, Chen TH. Source: Diabetic Medicine : a Journal of the British Diabetic Association. 2003 September; 20(9): 727-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12925052
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Association of the VEGF gene with proliferative diabetic retinopathy but not proteinuria in diabetes. Author(s): Ray D, Mishra M, Ralph S, Read I, Davies R, Brenchley P. Source: Diabetes. 2004 March; 53(3): 861-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14988276
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Automated detection of diabetic retinopathy in a fundus photographic screening population. Author(s): Larsen N, Godt J, Grunkin M, Lund-Andersen H, Larsen M. Source: Investigative Ophthalmology & Visual Science. 2003 February; 44(2): 767-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12556412
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Automated detection of diabetic retinopathy in digital retinal images: a tool for diabetic retinopathy screening. Author(s): Usher D, Dumskyj M, Himaga M, Williamson TH, Nussey S, Boyce J. Source: Diabetic Medicine : a Journal of the British Diabetic Association. 2004 January; 21(1): 84-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14706060
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Automated detection of fundus photographic red lesions in diabetic retinopathy. Author(s): Larsen M, Godt J, Larsen N, Lund-Andersen H, Sjolie AK, Agardh E, Kalm H, Grunkin M, Owens DR. Source: Investigative Ophthalmology & Visual Science. 2003 February; 44(2): 761-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12556411
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Awareness of diabetic retinopathy among diabetics. Author(s): Verma L, Elankumaran P, Prakash G, Venkatesh P, Tewari HK. Source: Indian J Ophthalmol. 2002 December; 50(4): 355. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12532507
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Awareness of diabetic retinopathy among diabetics. Author(s): Roy P. Source: Indian J Ophthalmol. 2003 December; 51(4): 365; Author Reply 365. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14750634
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Background diabetic retinopathy in Harare, Zimbabwe. Author(s): Bartels MC, Macheka BM, Guramantunhu S, Scheenloop JJ, Stilma JS. Source: Trop Doct. 1999 July; 29(3): 189-90. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10448253
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Barriers to compliance with screening guidelines for diabetic retinopathy. Author(s): Mukamel DB, Bresnick GH, Wang Q, Dickey CF. Source: Ophthalmic Epidemiology. 1999 March; 6(1): 61-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10384685
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Barriers to prevention of vision loss caused by diabetic retinopathy. Author(s): Klein R. Source: Archives of Ophthalmology. 1997 August; 115(8): 1073-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9258233
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Basement membrane abnormalities in human eyes with diabetic retinopathy. Author(s): Ljubimov AV, Burgeson RE, Butkowski RJ, Couchman JR, Zardi L, Ninomiya Y, Sado Y, Huang ZS, Nesburn AB, Kenney MC. Source: The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society. 1996 December; 44(12): 1469-79. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8985139
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Beneficial effect of pancreas and kidney transplantation on advanced diabetic retinopathy. Author(s): Koznarova R, Saudek F, Sosna T, Adamec M, Jedinakova T, Boucek P, Bartos V, Lanska V. Source: Cell Transplantation. 2000 November-December; 9(6): 903-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11202576
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Benefits of training junior physicians to detect diabetic retinopathy--the Glasgow experience. Author(s): Bibby K, Barrie T, Patterson KR, MacCuish AC. Source: Journal of the Royal Society of Medicine. 1992 June; 85(6): 326-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1625263
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Benfotiamine blocks three major pathways of hyperglycemic damage and prevents experimental diabetic retinopathy. Author(s): Hammes HP, Du X, Edelstein D, Taguchi T, Matsumura T, Ju Q, Lin J, Bierhaus A, Nawroth P, Hannak D, Neumaier M, Bergfeld R, Giardino I, Brownlee M. Source: Nature Medicine. 2003 March; 9(3): 294-9. Epub 2003 February 18. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12592403
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Beyond retinal screening: digital imaging in the assessment and follow-up of patients with diabetic retinopathy. Author(s): Kerr D, Cavan DA, Jennings B, Dunnington C, Gold D, Crick M. Source: Diabetic Medicine : a Journal of the British Diabetic Association. 1998 October; 15(10): 878-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9796890
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BglII gene polymorphism of the alpha2beta1 integrin gene is a risk factor for diabetic retinopathy in Caucasians with type 2 diabetes. Author(s): Petrovic MG, Hawlina M, Peterlin B, Petrovic D. Source: Journal of Human Genetics. 2003; 48(9): 457-60. Epub 2003 August 23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12938014
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Binocular indirect panretinal laser photocoagulation for the treatment of proliferative diabetic retinopathy. Author(s): Gurelik G, Coney JM, Zakov ZN. Source: Ophthalmic Surgery, Lasers & Imaging : the Official Journal of the International Society for Imaging in the Eye. 2004 March-April; 35(2): 94-102. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15088818
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Biochemical abnormalities in vitreous of humans with proliferative diabetic retinopathy. Author(s): Sebag J, Buckingham B, Charles MA, Reiser K. Source: Archives of Ophthalmology. 1992 October; 110(10): 1472-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1417549
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Blocking angiogenesis in diabetic retinopathy. Author(s): Bonn D. Source: Lancet. 1996 August 31; 348(9027): 604. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8815360
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Blood glucose and diabetic retinopathy. Author(s): Orosz L, Udvardy M, Feher A, Vincze P, Madacsy L. Source: Bmj (Clinical Research Ed.). 1992 May 9; 304(6836): 1244-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1515807
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Blood glucose concentrations and progression of diabetic retinopathy. Author(s): Wolff SP. Source: Bmj (Clinical Research Ed.). 1992 February 22; 304(6825): 505-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1547434
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Blood glucose concentrations and progression of diabetic retinopathy: the seven year results of the Oslo study. Author(s): Brinchmann-Hansen O, Dahl-Jorgensen K, Sandvik L, Hanssen KF. Source: Bmj (Clinical Research Ed.). 1992 January 4; 304(6818): 19-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1734985
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Blood pressure control and diabetic retinopathy. Author(s): Klein R, Klein BE. Source: The British Journal of Ophthalmology. 2002 April; 86(4): 365-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11914198
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Blood-retina barrier permeability and its relation to the progression of diabetic retinopathy in type 1 diabetics. An 8-year follow-up study. Author(s): Engler C, Krogsaa B, Lund-Andersen H. Source: Graefe's Archive for Clinical and Experimental Ophthalmology = Albrecht Von Graefes Archiv Fur Klinische Und Experimentelle Ophthalmologie. 1991; 229(5): 442-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1937077
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Bovine factor VIII derivative in the treatment of non-proliferative diabetic retinopathy. Author(s): Bandello F, Lattanzio R, Maestranzi G, Brancato R. Source: Ophthalmologica. Journal International D'ophtalmologie. International Journal of Ophthalmology. Zeitschrift Fur Augenheilkunde. 1995; 209(3): 149-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7630622
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Bowman Lecture 1998. Diabetic retinopathy: some cellular, molecular and therapeutic considerations. Author(s): Archer DB. Source: Eye (London, England). 1999 August; 13 ( Pt 4): 497-523. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10692923
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Breakdown of the blood-aqueous barrier after argon laser panretinal photocoagulation for proliferative diabetic retinopathy. Author(s): Moriarty AP, Spalton DJ, Shilling JS, Ffytche TJ, Bulsara M. Source: Ophthalmology. 1996 May; 103(5): 833-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8637696
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Can a cilio-retinal artery influence diabetic retinopathy? Author(s): Tong L. Source: The British Journal of Ophthalmology. 2003 July; 87(7): 929. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12812912
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Cataract surgery in patients with diabetic retinopathy: visual outcome, progression of diabetic retinopathy, and incidence of diabetic macular oedema. Author(s): Krepler K, Biowski R, Schrey S, Jandrasits K, Wedrich A. Source: Graefe's Archive for Clinical and Experimental Ophthalmology = Albrecht Von Graefes Archiv Fur Klinische Und Experimentelle Ophthalmologie. 2002 September; 240(9): 735-8. Epub 2002 August 21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12271370
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CD4-CD8 and CD28 expression in T cells infiltrating the vitreous fluid in patients with proliferative diabetic retinopathy: a flow cytometric analysis. Author(s): Canton A, Martinez-Caceres EM, Hernandez C, Espejo C, Garcia-Arumi J, Simo R. Source: Archives of Ophthalmology. 2004 May; 122(5): 743-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15136323
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Changes in vitreous concentrations of human hepatocyte growth factor (hHGF) in proliferative diabetic retinopathy: implications for intraocular hHGF production. Author(s): Nishimura M, Ikeda T, Ushiyama M, Kinoshita S, Yoshimura M. Source: Clinical Science (London, England : 1979). 2000 January; 98(1): 9-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10600653
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Changes of nailfold microcirculation in patients of type II diabetes mellitus with diabetic retinopathy. Author(s): Yi Y, Baoyu W, Shenyuan Y, Liangxiang Z, Hanqing F, Yuantao L. Source: Chinese Medical Sciences Journal = Chung-Kuo I Hsueh K'o Hsueh Tsa Chih / Chinese Academy of Medical Sciences. 1999 December; 14(4): 233-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12894899
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Circulating antipericyte autoantibodies in diabetic retinopathy. Author(s): Attawia MA, Nayak RC. Source: Retina (Philadelphia, Pa.). 1999; 19(5): 390-400. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10546933
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Clinical outcomes following laser photocoagulation treatment for diabetic retinopathy at a large Australian ophthalmic hospital. Author(s): Yi Q, Bamroongsuk P, McCarty DJ, Mukesh BN, Harper CA. Source: Clinical & Experimental Ophthalmology. 2003 August; 31(4): 305-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12880454
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Combining phacoemulsification and vitrectomy in patients with proliferative diabetic retinopathy. Author(s): Lahey JM, Francis RR, Kearney JJ, Cheung M. Source: Current Opinion in Ophthalmology. 2004 June; 15(3): 192-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15118505
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Combining phacoemulsification with pars plana vitrectomy in patients with proliferative diabetic retinopathy: a series of 223 cases. Author(s): Lahey JM, Francis RR, Kearney JJ. Source: Ophthalmology. 2003 July; 110(7): 1335-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12867387
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Comparison of optometry vs digital photography screening for diabetic retinopathy in a single district. Author(s): Tu KL, Palimar P, Sen S, Mathew P, Khaleeli A. Source: Eye (London, England). 2004 January; 18(1): 3-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14707956
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Comparison of the amblyopia treatment study HOTV and electronic-early treatment of diabetic retinopathy study visual acuity protocols in children aged 5 to 12 years. Author(s): Rice ML, Leske DA, Holmes JM. Source: American Journal of Ophthalmology. 2004 February; 137(2): 278-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14962417
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Comparison of two reference standards in validating two field mydriatic digital photography as a method of screening for diabetic retinopathy. Author(s): Scanlon PH, Malhotra R, Greenwood RH, Aldington SJ, Foy C, Flatman M, Downes S. Source: The British Journal of Ophthalmology. 2003 October; 87(10): 1258-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14507762
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Comparison of two, three and four 45 degrees image fields obtained with the Topcon CRW6 nonmydriatic camera for screening for diabetic retinopathy. Author(s): Perrier M, Boucher MC, Angioi K, Gresset JA, Olivier S. Source: Can J Ophthalmol. 2003 December; 38(7): 569-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14740798
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Comparison of venous filling times and SLO findings at each quadrant region in diabetic retinopathy. Author(s): Kang HR, Yang YS. Source: Korean J Ophthalmol. 2003 December; 17(2): 133-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14717492
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Concomitance of diabetic retinopathy and proteinuria accelerates the rate of decline of kidney function in type 2 diabetic patients. Author(s): Trevisan R, Vedovato M, Mazzon C, Coracina A, Iori E, Tiengo A, Del Prato S. Source: Diabetes Care. 2002 November; 25(11): 2026-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12401751
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Correlation between erythrocyte aldose reductase level and human diabetic retinopathy. Author(s): Oishi N, Kubo E, Takamura Y, Maekawa K, Tanimoto T, Akagi Y. Source: The British Journal of Ophthalmology. 2002 December; 86(12): 1363-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12446366
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Cost-effectiveness of glycemic control and ophthalmological care in diabetic retinopathy. Author(s): Polak BC, Crijns H, Casparie AF, Niessen LW. Source: Health Policy (Amsterdam, Netherlands). 2003 April; 64(1): 89-97. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12644331
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Coverage in screening for diabetic retinopathy according to screening provision: results from a national survey in England and Wales. Author(s): Wilson A, Baker R, Thompson J, Grimshaw G. Source: Diabetic Medicine : a Journal of the British Diabetic Association. 2004 March; 21(3): 271-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15008839
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Current status of screening for diabetic retinopathy in the UK. Author(s): Warburton T. Source: Diabetic Medicine : a Journal of the British Diabetic Association. 2003 August; 20(8): 690. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12873303
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Current status of screening for diabetic retinopathy in the UK. Author(s): Morris A, Slattery J, Olson J, Leese G, Harvey R. Source: Diabetic Medicine : a Journal of the British Diabetic Association. 2003 July; 20(7): 603-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12823247
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Deficit of somatostatin-like immunoreactivity in the vitreous fluid of diabetic patients: possible role in the development of proliferative diabetic retinopathy. Author(s): Simo R, Lecube A, Sararols L, Garcia-Arumi J, Segura RM, Casamitjana R, Hernandez C. Source: Diabetes Care. 2002 December; 25(12): 2282-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12453974
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Diabetes duration may modify the association between genetic variation in the glycoprotein Ia subunit of the platelet collagen receptor and risk of severe diabetic retinopathy: a working hypothesis. Author(s): Reiner AP, Agardh E, Teramura G, Gaur P, Gaur LK, Agardh CD. Source: Thrombosis and Haemostasis. 2003 January; 89(1): 142-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12540964
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Diabetic papillopathy as a risk factor for progression of diabetic retinopathy. Author(s): Bandello F, Menchini F. Source: Retina (Philadelphia, Pa.). 2004 February; 24(1): 183-4; Author Reply 184. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15076973
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Diabetic papillopathy as a risk factor for progression of diabetic retinopathy: reply. Author(s): Lee SY, Ang CL. Source: Retina (Philadelphia, Pa.). 2004 February; 24(1): 184-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15076975
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Diabetic retinopathy and diabetic macular edema: pathophysiology, screening, and novel therapies. Author(s): Ciulla TA, Amador AG, Zinman B. Source: Diabetes Care. 2003 September; 26(9): 2653-64. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12941734
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Diabetic retinopathy and serum lipoprotein subclasses in the DCCT/EDIC cohort. Author(s): Lyons TJ, Jenkins AJ, Zheng D, Lackland DT, McGee D, Garvey WT, Klein RL. Source: Investigative Ophthalmology & Visual Science. 2004 March; 45(3): 910-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14985310
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Diabetic retinopathy in African Americans: vision impairment, prevalence, incidence, and risk factors. Author(s): Baker RS. Source: International Ophthalmology Clinics. 2003 Fall; 43(4): 105-22. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14574205
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Diabetic retinopathy in Euro-Brazilian type 2 diabetic patients: relationship with polymorphisms in the aldose reductase, the plasminogen activator inhibitor-1 and the methylenetetrahydrofolate reductase genes. Author(s): Santos KG, Tschiedel B, Schneider J, Souto K, Roisenberg I. Source: Diabetes Research and Clinical Practice. 2003 August; 61(2): 133-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12951282
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Diabetic retinopathy in Oman: a hospital based study. Author(s): Khandekar R, Al Lawatii J, Mohammed AJ, Al Raisi A. Source: The British Journal of Ophthalmology. 2003 September; 87(9): 1061-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12928265
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Diabetic retinopathy with repeated amaurosis fugax caused by orthostatic hypotension. Author(s): Mimura T, Funatsu H, Kitano S, Amano S, Haruyama K, Shimizu E, Araie M, Hori S. Source: American Journal of Ophthalmology. 2003 November; 136(5): 930-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14597053
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Diabetic retinopathy. Author(s): Stefansson E. Source: The New England Journal of Medicine. 2004 June 10; 350(24): 2525-6; Author Reply 2525-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15190152
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Diabetic retinopathy. Author(s): Grassi G. Source: Minerva Med. 2003 December; 94(6): 419-35. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14976470
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Diabetic retinopathy. Author(s): Frank RN. Source: The New England Journal of Medicine. 2004 January 1; 350(1): 48-58. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14702427
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Diabetic retinopathy: management update. Author(s): Nwosu SN. Source: Niger Postgrad Med J. 2003 June; 10(2): 115-20. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14567050
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Diabetic retinopathy: medical management and assessment. Author(s): Delli Castelli M, Leslie RD. Source: Hosp Med. 2003 July; 64(7): 400-3. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12886849
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Diabetic retinopathy: should this patient receive laser treatment? Author(s): Chew EY, Dowler J, Flynn H. Source: The British Journal of Ophthalmology. 2004 March; 88(3): 433. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14977783
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Diabetic retinopathy: should this patient receive laser treatment? Overview. Author(s): Chew E. Source: The British Journal of Ophthalmology. 2004 March; 88(3): 436-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14977786
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Diabetic retinopathy: yet another reason for a comprehensive eye-care programme for Australian Aborigines and Torres Strait Islanders. Author(s): McCarty CA. Source: Clinical & Experimental Ophthalmology. 2003 February; 31(1): 6-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12580887
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Diverse NF-kappaB expression in epiretinal membranes after human diabetic retinopathy and proliferative vitreoretinopathy. Author(s): Harada C, Harada T, Mitamura Y, Quah HM, Ohtsuka K, Kotake S, Ohno S, Wada K, Takeuchi S, Tanaka K. Source: Molecular Vision [electronic Resource]. 2004 January 15; 10: 31-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14737065
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Does pregnancy accelerate the rate of progression of diabetic retinopathy? Author(s): Sheth BP. Source: Curr Diab Rep. 2002 August; 2(4): 327-30. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12643192
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Early complement activation and decreased levels of glycosylphosphatidylinositolanchored complement inhibitors in human and experimental diabetic retinopathy. Author(s): Zhang J, Gerhardinger C, Lorenzi M. Source: Diabetes. 2002 December; 51(12): 3499-504. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12453906
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Early improvement of unstable diabetic retinopathy after solitary pancreas transplantation. Author(s): Giannarelli R, Coppelli A, Sartini MS, Aragona M, Boggi U, Mosca F, Nardi M, Del Prato S, Marchetti P. Source: Diabetes Care. 2002 December; 25(12): 2358-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12453991
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Effect of a growth hormone receptor antagonist on proliferative diabetic retinopathy. Author(s): Chantelau E. Source: Ophthalmology. 2002 December; 109(12): 2187; Author Reply 2187-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12466154
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Effect of video display on the grading of diabetic retinopathy. Author(s): Costen MT, Newsom RS, Parkin B, Marsh CS, Mehta RL, Luff AJ, Canning CR. Source: Eye (London, England). 2004 February; 18(2): 169-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14762410
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Effectiveness and safety of screening for diabetic retinopathy with two nonmydriatic digital images compared with the seven standard stereoscopic photographic fields. Author(s): Boucher MC, Gresset JA, Angioi K, Olivier S. Source: Can J Ophthalmol. 2003 December; 38(7): 557-68. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14740797
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Efficacy and reliability of fundus digital camera as a screening tool for diabetic retinopathy in Kuwait. Author(s): Al Sabti K, Raizada S, Wani VB, Al Ajmi M, Gayed I, Sugathan TN. Source: Journal of Diabetes and Its Complications. 2003 July-August; 17(4): 229-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12810247
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Elevated adrenomedullin in the vitreous of patients with diabetic retinopathy. Author(s): Ito S, Fujisawa K, Sakamoto T, Ishibashi T. Source: Ophthalmologica. Journal International D'ophtalmologie. International Journal of Ophthalmology. Zeitschrift Fur Augenheilkunde. 2003 January-February; 217(1): 53-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12566874
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Elevated gamma-aminobutyric acid, glutamate, and vascular endothelial growth factor levels in the vitreous of patients with proliferative diabetic retinopathy. Author(s): Ambati J, Chalam KV, Chawla DK, D'Angio CT, Guillet EG, Rose SJ, Vanderlinde RE, Ambati BK. Source: Archives of Ophthalmology. 1997 September; 115(9): 1161-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9298058
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Entoptic foveal avascular zone measurement and diabetic retinopathy. Author(s): Hilmantel G, Applegate RA, van Heuven WA, Stowers SP, Bradley A, Lee BL. Source: Optometry and Vision Science : Official Publication of the American Academy of Optometry. 1999 December; 76(12): 826-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10612403
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Epidemiology of diabetic retinopathy. Author(s): Chew EY. Source: Hosp Med. 2003 July; 64(7): 396-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12886848
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Evaluating the management of diabetic retinopathy in a teaching center. Author(s): Pharmakakis NM, Petropoulos IK, Peristeropoulos PA, Vantzou CV, Koliopoulos JX. Source: Eur J Ophthalmol. 2002 November-December; 12(6): 488-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12516532
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Evaluation of a district-wide screening programme for diabetic retinopathy utilizing trained optometrists using slit-lamp and Volk lenses. Author(s): Hulme SA, Tin-U A, Hardy KJ, Joyce PW. Source: Diabetic Medicine : a Journal of the British Diabetic Association. 2002 September; 19(9): 741-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12207810
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Evaluation of a new non-mydriatic digital camera for detection of diabetic retinopathy. Author(s): Massin P, Erginay A, Ben Mehidi A, Vicaut E, Quentel G, Victor Z, Marre M, Guillausseau PJ, Gaudric A. Source: Diabetic Medicine : a Journal of the British Diabetic Association. 2003 August; 20(8): 635-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12873290
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Evaluation of retinal nerve fiber layer thickness in diabetic retinopathy after panretinal photocoagulation. Author(s): Hsu SY, Chung CP. Source: Kaohsiung J Med Sci. 2002 August; 18(8): 397-400. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12476683
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Evidence for photoreceptor changes in patients with diabetic retinopathy. Author(s): Holopigian K, Greenstein VC, Seiple W, Hood DC, Carr RE. Source: Investigative Ophthalmology & Visual Science. 1997 October; 38(11): 2355-65. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9344359
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Exercise training in individuals with diabetic retinopathy and blindness. Author(s): Bernbaum M, Albert SG, Cohen JD. Source: Archives of Physical Medicine and Rehabilitation. 1989 August; 70(8): 605-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2764690
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Exogenous estrogen exposures and changes in diabetic retinopathy. The Wisconsin Epidemiologic Study of Diabetic Retinopathy. Author(s): Klein BE, Klein R, Moss SE. Source: Diabetes Care. 1999 December; 22(12): 1984-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10587830
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Extracts from "concise clinical evidence". Commentary: treatment of diabetic retinopathy. Author(s): Kohner E. Source: Bmj (Clinical Research Ed.). 2003 May 10; 326(7397): 1023-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12742899
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Extracts from "concise clinical evidence". Diabetic retinopathy. Author(s): Harding S. Source: Bmj (Clinical Research Ed.). 2003 May 10; 326(7397): 1023-5. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12742927
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Exudative age-related macular degeneration in patients with diabetic retinopathy and its relation to retinal laser photocoagulation. Author(s): Zylbermann R, Landau D, Rozenman Y, Abrahami S, Pollack A. Source: Eye (London, England). 1997; 11 ( Pt 6): 872-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9537150
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Factors that influence the decision to receive treatment for proliferative diabetic retinopathy. Author(s): Reno PL, Arfken CL, Heins JM, Fisher EB Jr. Source: Diabetes Educ. 1997 November-December; 23(6): 653-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9416028
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Familial clustering of diabetic retinopathy in South Indian Type 2 diabetic patients. Author(s): Rema M, Saravanan G, Deepa R, Mohan V. Source: Diabetic Medicine : a Journal of the British Diabetic Association. 2002 November; 19(11): 910-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12421427
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Fas-mediated apoptosis in human lens epithelial cells of cataracts associated with diabetic retinopathy. Author(s): Okamura N, Ito Y, Shibata MA, Ikeda T, Otsuki Y. Source: Medical Electron Microscopy : Official Journal of the Clinical Electron Microscopy Society of Japan. 2002 December; 35(4): 234-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12658358
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Fatty acid binding protein gene 2 polymorphism is not associated with diabetic retinopathy in Japanese type 2 diabetic patients. Author(s): Yoshioka K, Yoshida T, Takakura Y, Umekawa T, Kogure A, Toda H, Yoshikawa T. Source: Hormone and Metabolic Research. Hormon- Und Stoffwechselforschung. Hormones Et Metabolisme. 2003 October; 35(10): 625-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14605999
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Fetal weight and progression of diabetic retinopathy. Author(s): McElvy SS, Demarini S, Miodovnik M, Khoury JC, Rosenn B, Tsang RC. Source: Obstetrics and Gynecology. 2001 April; 97(4): 587-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11275032
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Five-year incidence of diabetic retinopathy in the Melbourne Visual Impairment Project. Author(s): McCarty DJ, Fu CL, Harper CA, Taylor HR, McCarty CA. Source: Clinical & Experimental Ophthalmology. 2003 October; 31(5): 397-402. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14516426
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Florid diabetic retinopathy (FDR): a long-term follow-up study. Author(s): Lattanzio R, Brancato R, Bandello FM, Azzolini C, Malegori A, Maestranzi G. Source: Graefe's Archive for Clinical and Experimental Ophthalmology = Albrecht Von Graefes Archiv Fur Klinische Und Experimentelle Ophthalmologie. 2001 March; 239(3): 182-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11405067
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Florid diabetic retinopathy and its systemic implications. Author(s): Lanzetta P, Bandello F, Menchini U, Brancato R. Source: Diabetes Nutr Metab. 1999 December; 12(6): 418-9. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10782564
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Fluidity and fatty acid components of erythrocyte membranes in diabetic retinopathy. Author(s): Yang G, Qiu H, Wang S, Deng H, Zhang S, Li L. Source: Zhonghua Yi Xue Za Zhi (Taipei). 2000 May; 63(5): 407-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10862451
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Fluorescein angiography of extreme peripheral retina and rubeosis iridis in proliferative diabetic retinopathy. Author(s): Terasaki H, Miyake Y, Mori M, Suzuki T, Kondo M. Source: Retina (Philadelphia, Pa.). 1999; 19(4): 302-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10458295
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Foreword: Evaluation of new treatment paradigms for diabetic retinopathy and macular edema. Author(s): Ferris FL 3rd. Source: Survey of Ophthalmology. 2002 December; 47 Suppl 2: S237. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12507624
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Foveal cone function in nonproliferative diabetic retinopathy and macular edema. Author(s): Weiner A, Christopoulos VA, Gussler CH, Adams DH, Kaufman SR, Kohn HD, Weidenthal DT. Source: Investigative Ophthalmology & Visual Science. 1997 June; 38(7): 1443-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9191608
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Foveal haemorrhages in diabetic retinopathy. Clinical characteristics and visual outcome. Author(s): Lahrmann C, Bek T. Source: Acta Ophthalmologica Scandinavica. 2000 April; 78(2): 169-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10794250
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Fractal dimension in diabetic retinopathy. Author(s): Hesse L. Source: Graefe's Archive for Clinical and Experimental Ophthalmology = Albrecht Von Graefes Archiv Fur Klinische Und Experimentelle Ophthalmologie. 1994 July; 232(7): 447-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7926879
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Free and total insulin-like growth factor I (IGF-I), IGF-binding protein-1 (IGFBP-1), and IGFBP-3 and their relationships to the presence of diabetic retinopathy and glomerular hyperfiltration in insulin-dependent diabetes mellitus. Author(s): Janssen JA, Jacobs ML, Derkx FH, Weber RF, van der Lely AJ, Lamberts SW. Source: The Journal of Clinical Endocrinology and Metabolism. 1997 September; 82(9): 2809-15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9284701
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Free insulin growth factor-I and vascular endothelial growth factor in the vitreous fluid of patients with proliferative diabetic retinopathy. Author(s): Simo R, Lecube A, Segura RM, Garcia Arumi J, Hernandez C. Source: American Journal of Ophthalmology. 2002 September; 134(3): 376-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12208249
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Free insulin-like growth factor 1 in the vitreous fluid of diabetic patients with proliferative diabetic retinopathy: a case-control study. Author(s): Simo R, Hernandez C, Segura RM, Garcia-Arumi J, Sararols L, Burgos R, Canton A, Mesa J. Source: Clinical Science (London, England : 1979). 2003 March; 104(3): 223-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12605576
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Frequency and patients' reported awareness of diabetic retinopathy among type 2 diabetic patients admitted to internal medicine wards. Author(s): Sadeh AD, Rosenblatt I, Rosenberger Y, Lazar M, Loewenstein A. Source: Diabetes Care. 2000 September; 23(9): 1436-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10977051
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From minimal background diabetic retinopathy to profuse sight threatening vitreoretinal haemorrhage: management issues in a case of pregestational diabetes and pregnancy. Author(s): Chatterjee S, Tsaloumas MD, Gee H, Lipkin G, Dunne FP. Source: Diabetic Medicine : a Journal of the British Diabetic Association. 2003 August; 20(8): 683-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12873299
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Functions of insulin and insulin receptor signaling in retina: possible implications for diabetic retinopathy. Author(s): Reiter CE, Gardner TW. Source: Progress in Retinal and Eye Research. 2003 July; 22(4): 545-62. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12742394
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General practitioners are the most important conveyors of information to their patients regarding diabetic retinopathy. Author(s): Livingston PM, Wood CA, Butler M, Oh J, Keefe JE, Taylor HR. Source: Diabetes Care. 1998 February; 21(2): 324-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9540007
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Genes and diabetic retinopathy. Author(s): Radha V, Rema M, Mohan V. Source: Indian J Ophthalmol. 2002 March; 50(1): 5-11. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12090088
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Genetic markers in early diabetic retinopathy of adolescents with type I diabetes. Author(s): Falck AA, Knip JM, Ilonen JS, Laatikainen LT. Source: Journal of Diabetes and Its Complications. 1997 July-August; 11(4): 203-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9201596
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Genetic risk factors in diabetic retinopathy. Author(s): Stewart LL, Field LL, Ross S, McArthur RG. Source: Diabetologia. 1993 December; 36(12): 1293-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8307258
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Genotyping and functional analysis of a polymorphic (CCTTT)(n) repeat of NOS2A in diabetic retinopathy. Author(s): Warpeha KM, Xu W, Liu L, Charles IG, Patterson CC, Ah-Fat F, Harding S, Hart PM, Chakravarthy U, Hughes AE. Source: The Faseb Journal : Official Publication of the Federation of American Societies for Experimental Biology. 1999 October; 13(13): 1825-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10506586
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Glial cell involvement in vascular occlusion of diabetic retinopathy. Author(s): Bek T. Source: Acta Ophthalmologica Scandinavica. 1997 June; 75(3): 239-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9253965
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Glycated haemoglobin, plasma glucose and diabetic retinopathy: cross-sectional and prospective analyses. Author(s): Liu QZ, Pettitt DJ, Hanson RL, Charles MA, Klein R, Bennett PH, Knowler WC. Source: Diabetologia. 1993 May; 36(5): 428-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8314447
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Glycoprotein deposition in vascular walls of diabetic retinopathy. A histopathological and immunohistochemical study. Author(s): Bek T, Ledet T. Source: Acta Ophthalmologica Scandinavica. 1996 August; 74(4): 385-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8883556
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Glycosylated hemoglobin and diabetic retinopathy. Author(s): Singh R, Prakash V, Shukla PK, Gautam S, Maurya OP. Source: Ann Ophthalmol. 1991 August; 23(8): 308-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1952641
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Graded corneal sensitivity for screening of diabetic retinopathy. Author(s): Saini JS, Mittal S. Source: Indian J Ophthalmol. 1996 December; 44(4): 219-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9251266
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Grading and disease management in national screening for diabetic retinopathy in England and Wales. Author(s): Harding S, Greenwood R, Aldington S, Gibson J, Owens D, Taylor R, Kohner E, Scanlon P, Leese G; Diabetic Retinopathy Grading and Disease Management Working Party. Source: Diabetic Medicine : a Journal of the British Diabetic Association. 2003 December; 20(12): 965-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14632697
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Grading diabetic retinopathy from a computer screen. Author(s): Leverton C. Source: The Journal of Audiovisual Media in Medicine. 1996 December; 19(4): 176. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9136176
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Gray-white, spherical deposition on retinal vessel associated with acute retinal necrosis and diabetic retinopathy in HTLV-I carriers. Author(s): Nakao K, Ohba N, Uemura A, Okubo A, Sameshima M, Hayami K. Source: Japanese Journal of Ophthalmology. 1998 November-December; 42(6): 490-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9886741
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Growth factor alterations in advanced diabetic retinopathy: a possible role of blood retina barrier breakdown. Author(s): Pfeiffer A, Spranger J, Meyer-Schwickerath R, Schatz H. Source: Diabetes. 1997 September; 46 Suppl 2: S26-30. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9285495
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Growth factors and diabetic retinopathy. Author(s): Paques M, Massin P, Gaudric A. Source: Diabetes & Metabolism. 1997 April; 23(2): 125-30. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9137900
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Growth factors and protein kinase C inhibitors as novel therapies for the medical management diabetic retinopathy. Author(s): Aiello LP, Cahill MT, Cavallerano JD. Source: Eye (London, England). 2004 February; 18(2): 117-25. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14762400
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Growth factors in proliferative diabetic retinopathy. Author(s): Khan ZA, Chakrabarti S. Source: Experimental Diabesity Research. 2003 October-December; 4(4): 287-301. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14668050
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Growth factors in retinal diseases: proliferative vitreoretinopathy, proliferative diabetic retinopathy, and retinal degeneration. Author(s): Wiedemann P. Source: Survey of Ophthalmology. 1992 March-April; 36(5): 373-84. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1566240
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Growth hormone suppression and nonproliferative diabetic retinopathy: a preliminary feasibility study. Author(s): Shumak SL, Grossman LD, Chew E, Kozousek V, George SR, Singer W, Harris AG, Zinman B. Source: Clinical and Investigative Medicine. Medecine Clinique Et Experimentale. 1990 October; 13(5): 287-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2276223
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Guidelines for screening for diabetic retinopathy revisited. Author(s): Klein R. Source: Ophthalmic Epidemiology. 1999 March; 6(1): 1-4. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10384679
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Haptoglobin genotype as a risk factor for diabetic retinopathy. Author(s): Nakhoul FM, Marsh S, Hochberg I, Leibu R, Miller BP, Levy AP. Source: Jama : the Journal of the American Medical Association. 2000 September 13; 284(10): 1244-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10979109
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Has the frequency of proliferative diabetic retinopathy declined in the US? Author(s): Klein R. Source: Diabetes Care. 2003 September; 26(9): 2691-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12941740
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Heart rate elevation and diabetic retinopathy in patients with type 2 diabetes mellitus and normoalbuminuria. Author(s): Imano E, Miyatsuka T, Motomura M, Kanda T, Matsuhisa M, Kajimoto Y, Yamasaki Y, Hori M. Source: Diabetes Research and Clinical Practice. 2001 June; 52(3): 185-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11323088
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Hemodynamic alterations in diabetic retinopathy. Author(s): Guven D, Ozdemir H, Hasanreisoglu B. Source: Ophthalmology. 1996 August; 103(8): 1245-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8764795
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Hemorheological alterations in patients with diabetic retinopathy. Author(s): Vekasi J, Marton ZS, Kesmarky G, Cser A, Russai R, Horvath B. Source: Clinical Hemorheology and Microcirculation. 2001; 24(1): 59-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11345235
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Hepatocyte growth factor in vitreous and serum from patients with proliferative diabetic retinopathy. Author(s): Canton A, Burgos R, Hernandez C, Mateo C, Segura RM, Mesa J, Simo R. Source: The British Journal of Ophthalmology. 2000 July; 84(7): 732-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10873984
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Hepatocyte growth factor in vitreous fluid of patients with proliferative diabetic retinopathy and other retinal disorders. Author(s): Katsura Y, Okano T, Noritake M, Kosano H, Nishigori H, Kado S, Matsuoka T. Source: Diabetes Care. 1998 October; 21(10): 1759-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9773744
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High cardiovascular disease mortality in subjects with visual impairment caused by diabetic retinopathy. Author(s): Rajala U, Pajunpaa H, Koskela P, Keinanen-Kiukaanniemi S. Source: Diabetes Care. 2000 July; 23(7): 957-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10895846
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High serum lipoprotein(a) levels in Korean type 2 diabetic patients with proliferative diabetic retinopathy. Author(s): Kim CH, Park HJ, Park JY, Hong SK, Yoon YH, Lee KU. Source: Diabetes Care. 1998 December; 21(12): 2149-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9839109
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Histopathology and regression of retinal hard exudates in diabetic retinopathy after reduction of elevated serum lipid levels. Author(s): Cusick M, Chew EY, Chan CC, Kruth HS, Murphy RP, Ferris FL 3rd. Source: Ophthalmology. 2003 November; 110(11): 2126-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14597519
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HLA typing is not predictive of proliferative diabetic retinopathy in patients with younger onset type 2 diabetes mellitus. Author(s): Mimura T, Amano S, Kato S, Araie M, Funatsu H, Kitano S, Shimizu E, Noma H, Yoshino O, Hori S. Source: The British Journal of Ophthalmology. 2004 February; 88(2): 303-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14736798
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HLA-DR3 and DR4 and their relation to the incidence and progression of diabetic retinopathy. Author(s): Wong TY, Cruickshank KJ, Klein R, Klein BE, Moss SE, Palta M, Riley WJ, Maclaren NK, Vadheim CM, Rotter JI. Source: Ophthalmology. 2002 February; 109(2): 275-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11825808
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Homocysteine levels during fasting and after methionine loading in adolescents with diabetic retinopathy and nephropathy. Author(s): Chiarelli F, Pomilio M, Mohn A, Tumini S, Vanelli M, Morgese G, Spagnoli A, Verrotti A. Source: The Journal of Pediatrics. 2000 September; 137(3): 386-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10969265
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How effective is the referral chain for diabetic retinopathy? Author(s): Jenkins L, Knight AH, Mayon-White V. Source: Diabetic Medicine : a Journal of the British Diabetic Association. 1989 September-October; 6(7): 645. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2527713
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How many steps of progression of diabetic retinopathy are meaningful? The Wisconsin epidemiologic study of diabetic retinopathy. Author(s): Klein R, Klein BE, Moss SE. Source: Archives of Ophthalmology. 2001 April; 119(4): 547-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11296020
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Human corneal epithelial basement membrane and integrin alterations in diabetes and diabetic retinopathy. Author(s): Ljubimov AV, Huang ZS, Huang GH, Burgeson RE, Gullberg D, Miner JH, Ninomiya Y, Sado Y, Kenney MC. Source: The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society. 1998 September; 46(9): 1033-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9705969
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Human vitreal prostaglandin levels and proliferative diabetic retinopathy. Author(s): Douros S, Phillips BA, Nadel A, Obstbaum SA. Source: Documenta Ophthalmologica. Advances in Ophthalmology. 2001 July; 103(1): 27-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11678158
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Hyperlipidemia, insulin-dependent diabetes mellitus, and rapidly progressive diabetic retinopathy and nephropathy in Prader-Willi syndrome with del(15)(q11.2q13). Author(s): Bassali R, Hoffman WH, Chen H, Tuck-Muller CM. Source: American Journal of Medical Genetics. 1997 August 22; 71(3): 267-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9268093
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Hyperoxia improves contrast sensitivity in early diabetic retinopathy. Author(s): Harris A, Arend O, Danis RP, Evans D, Wolf S, Martin BJ. Source: The British Journal of Ophthalmology. 1996 March; 80(3): 209-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8703857
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Hypertension and diabetic retinopathy--what's the story? Author(s): Gillow JT, Gibson JM, Dodson PM. Source: The British Journal of Ophthalmology. 1999 September; 83(9): 1083-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10460781
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Impact of diabetic retinopathy screening on a British district population: case detection and blindness prevention in an evidence-based model. Author(s): Bachmann MO, Nelson SJ. Source: Journal of Epidemiology and Community Health. 1998 January; 52(1): 45-52. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9604041
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Impaired color vision associated with diabetic retinopathy: Early Treatment Diabetic Retinopathy Study Report No. 15. Author(s): Fong DS, Barton FB, Bresnick GH. Source: American Journal of Ophthalmology. 1999 November; 128(5): 612-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10577530
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Improving diabetic retinopathy screening. Author(s): Jackson W. Source: Diabetes Care. 2002 August; 25(8): 1477-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12145254
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Incidence and progression of diabetic retinopathy in Hispanics and non-Hispanic whites with type 2 diabetes. San Luis Valley Diabetes Study, Colorado. Author(s): Tudor SM, Hamman RF, Baron A, Johnson DW, Shetterly SM. Source: Diabetes Care. 1998 January; 21(1): 53-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9538971
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Incidence of and risk factors for diabetic retinopathy in Isfahan, Iran. Author(s): Janghorbani M, Amini M, Ghanbari H, Safaiee H. Source: Ophthalmic Epidemiology. 2003 April; 10(2): 81-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12660857
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Incidence of diabetic retinopathy in the Barbados Eye Studies. Author(s): Leske MC, Wu SY, Hennis A, Nemesure B, Hyman L, Schachat A; Barbados Eye Studies Group. Source: Ophthalmology. 2003 May; 110(5): 941-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12750094
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Increased concentration of pentosidine, an advanced glycation end product, and interleukin-6 in the vitreous of patients with proliferative diabetic retinopathy. Author(s): Nakamura N, Hasegawa G, Obayashi H, Yamazaki M, Ogata M, Nakano K, Yoshikawa T, Watanabe A, Kinoshita S, Fujinami A, Ohta M, Imamura Y, Ikeda T. Source: Diabetes Research and Clinical Practice. 2003 August; 61(2): 93-101. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12951277
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Increased serum IGF-I during pregnancy is associated with progression of diabetic retinopathy. Author(s): Lauszus FF, Klebe JG, Bek T, Flyvbjerg A. Source: Diabetes. 2003 March; 52(3): 852-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12606530
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Influence of successful pancreaticorenal transplantation on diabetic retinopathy. Author(s): Caldara R, Bandello F, Vigano C, Secchi A, Castoldi R, Caldi M, Di Carlo V, Torri G, Pozza G, Brancato R. Source: Transplantation Proceedings. 1994 April; 26(2): 490. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8171518
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Insertion/deletion plasminogen activator inhibitor 1 and insertion/deletion angiotensin-converting enzyme gene polymorphisms in diabetic retinopathy in type 2 diabetes. Author(s): Globocnik-Petrovic M, Hawlina M, Peterlin B, Petrovic D. Source: Ophthalmologica. Journal International D'ophtalmologie. International Journal of Ophthalmology. Zeitschrift Fur Augenheilkunde. 2003 May-June; 217(3): 219-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12660488
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Instant electronic imaging systems are superior to Polaroid at detecting sightthreatening diabetic retinopathy. Author(s): Ryder RE, Kong N, Bates AS, Sim J, Welch J, Kritzinger EE. Source: Diabetic Medicine : a Journal of the British Diabetic Association. 1998 March; 15(3): 254-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9545128
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Interferon alpha-2a for proliferative diabetic retinopathy after complete laser panretinal photocoagulation treatment. Author(s): Leibovitch I, Loewenstein A, Alster Y, Rosenblatt I, Lazar M, Yassur Y, Rubinstein A. Source: Ophthalmic Surgery, Lasers & Imaging : the Official Journal of the International Society for Imaging in the Eye. 2004 January-February; 35(1): 16-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14750758
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Interleukin-8, nitric oxide and glutathione status in proliferative vitreoretinopathy and proliferative diabetic retinopathy. Author(s): Cicik E, Tekin H, Akar S, Ekmekci OB, Donma O, Koldas L, Ozkan S. Source: Ophthalmic Research. 2003 September-October; 35(5): 251-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12920337
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Inter-observer comparisons of ophthalmoscopic assessment of diabetic retinopathy. Author(s): Lienert RT. Source: Australian and New Zealand Journal of Ophthalmology. 1989 November; 17(4): 363-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2624726
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Intravitreal triamcinolone acetonide as an additional tool in pars plana vitrectomy for proliferative diabetic retinopathy. Author(s): Jonas JB, Sofker A, Degenring R. Source: Eur J Ophthalmol. 2003 June; 13(5): 468-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12841570
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Intravitreous leptin concentrations in patients with proliferative diabetic retinopathy. Author(s): Hernandez C, Lecube A, Castellanos JM, Segura RM, Garat M, Garcia-Arumi J, Simo R. Source: Retina (Philadelphia, Pa.). 2004 February; 24(1): 30-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15076941
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Is blood pressure a predictor of the incidence or progression of diabetic retinopathy? Author(s): Klein R, Klein BE, Moss SE, Davis MD, DeMets DL. Source: Archives of Internal Medicine. 1989 November; 149(11): 2427-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2684072
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Is digital image compression acceptable within diabetic retinopathy screening? Author(s): Basu A, Kamal AD, Illahi W, Khan M, Stavrou P, Ryder RE. Source: Diabetic Medicine : a Journal of the British Diabetic Association. 2003 September; 20(9): 766-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12925059
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Is medical treatment for diabetic retinopathy still an unreal dream? Author(s): Giusti C. Source: Medical Hypotheses. 2002 December; 59(6): 706-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12445513
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Is serum cholesterol associated with progression of diabetic retinopathy or macular edema in persons with younger-onset diabetes of long duration? Author(s): Klein BE, Klein R, Moss SE. Source: American Journal of Ophthalmology. 1999 November; 128(5): 652-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10577544
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Kallistatin in human ocular tissues: reduced levels in vitreous fluids from patients with diabetic retinopathy. Author(s): Ma JX, King LP, Yang Z, Crouch RK, Chao L, Chao J. Source: Current Eye Research. 1996 November; 15(11): 1117-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8950506
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Keeping good vision with diabetic retinopathy: a nursing responsibility. Author(s): Smith SS. Source: The Abnf Journal : Official Journal of the Association of Black Nursing Faculty in Higher Education, Inc. 1996 May-June; 7(3): 81-4. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8826167
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Krypton laser for proliferative diabetic retinopathy: the Krypton Argon Regression of Neovascularization Study. Author(s): Singerman LJ, Ferris FL 3rd, Mowery RP, Brucker AJ, Murphy RP, Lerner BC, Mincey GJ. Source: J Diabet Complications. 1988 October-December; 2(4): 189-96. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2466855
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Lack of association between the heparan sulfate proteoglycan gene polymorphism and diabetic nephropathy in Japanese NIDDM with proliferative diabetic retinopathy. Author(s): Fujita H, Narita T, Meguro H, Ishii T, Hanyu O, Suzuki K, Ito S. Source: Renal Failure. 1999 November; 21(6): 659-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10586428
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Laser management of diabetic retinopathy. Author(s): Dowler JG. Source: Journal of the Royal Society of Medicine. 2003 June; 96(6): 277-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12782691
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Lasers and diabetic retinopathy: the art of gentle destruction. Author(s): Petrovic V, Bhisitkul RB. Source: Diabetes Technology & Therapeutics. 1999 Summer; 1(2): 177-87. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11475290
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Life expectancy and diabetic retinopathy. Author(s): Kirstein MD. Source: J Am Optom Assoc. 1989 July; 60(7): 503. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2760393
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Lipid peroxidation and diabetic retinopathy. Author(s): Kumar RS, Anthrayose CV, Iyer KV, Vimala B, Shashidhar S. Source: Indian Journal of Medical Sciences. 2001 March; 55(3): 133-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11482166
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Lipoprotein(a) as an independent risk factor for diabetic retinopathy in male patients in non-insulin-dependent diabetes mellitus. Author(s): Onuma T, Kikuchi T, Shimura M, Tsutsui M, Matsui J, Boku A, Takebe K. Source: The Tohoku Journal of Experimental Medicine. 1994 June; 173(2): 209-16. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7817385
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Longitudinal studies of incidence and progression of diabetic retinopathy assessed by retinal photography in pima indians. Author(s): Looker HC, Krakoff J, Knowler WC, Bennett PH, Klein R, Hanson RL. Source: Diabetes Care. 2003 February; 26(2): 320-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12547856
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Longitudinal study of a cohort of people with diabetes screened by the Exeter Diabetic Retinopathy Screening Programme. Author(s): Ling R, Ramsewak V, Taylor D, Jacob J. Source: Eye (London, England). 2002 March; 16(2): 140-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11988813
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Long-term glycaemic control and diabetic retinopathy. Author(s): McCance DR, Hadden DR, Atkinson AB, Archer DB, Kennedy L. Source: Lancet. 1989 October 7; 2(8667): 824-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2571758
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Long-term metabolic control and diabetic retinopathy. Author(s): McNally PG, Swift P, Burden AC, Hearnshaw JR. Source: Lancet. 1989 November 18; 2(8673): 1227. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2572943
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Loss of myelinated retinal nerve fibres in diabetic retinopathy. Author(s): Gentile RC, Torqueti-Costa L, Bertolucci A. Source: The British Journal of Ophthalmology. 2002 December; 86(12): 1447. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12446391
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Low content of the natural ocular anti-angiogenic agent pigment epithelium-derived factor (PEDF) in aqueous humor predicts progression of diabetic retinopathy. Author(s): Boehm BO, Lang G, Volpert O, Jehle PM, Kurkhaus A, Rosinger S, Lang GK, Bouck N. Source: Diabetologia. 2003 March; 46(3): 394-400. Epub 2003 March 01. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12687338
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Macular recovery during onset and development of diabetic retinopathy in childhood and adolescence. Author(s): Frost-Larsen K, Lund-Anderson C, Starup K. Source: Acta Ophthalmol (Copenh). 1989 August; 67(4): 401-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2801042
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Massive subretinal bleed in a patient with background diabetic retinopathy and on treatment with warfarin. Author(s): Raj A, Sekhri R, Salam A, Priya P. Source: Eye (London, England). 2003 July; 17(5): 649-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12855977
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Mechanisms for monitoring changes in retinal status following therapeutic intervention in diabetic retinopathy. Author(s): Lund-Andersen H. Source: Survey of Ophthalmology. 2002 December; 47 Suppl 2: S270-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12507629
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Medical treatment of diabetic retinopathy. Author(s): Donaldson M, Dodson PM. Source: Eye (London, England). 2003 July; 17(5): 550-62. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12855958
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Midterm visual outcome and progression of diabetic retinopathy following cataract surgery. Midterm outcome of cataract surgery in diabetes. Author(s): Schrey S, Krepler K, Biowski R, Wedrich A. Source: Ophthalmologica. Journal International D'ophtalmologie. International Journal of Ophthalmology. Zeitschrift Fur Augenheilkunde. 2002 September-October; 216(5): 337-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12424399
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Molecular genetics of microvascular disease in diabetic retinopathy. Author(s): Warpeha KM, Chakravarthy U. Source: Eye (London, England). 2003 April; 17(3): 305-11. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12724690
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Molecular mechanisms of retinal neovascularization in diabetic retinopathy. Author(s): Takagi H. Source: Intern Med. 2003 March; 42(3): 299-301. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12705804
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MTHFR gene polymorphism as a risk factor for diabetic retinopathy in type 2 diabetic patients without serum creatinine elevation. Author(s): Maeda M, Yamamoto I, Fukuda M, Nishida M, Fujitsu J, Nonen S, Igarashi T, Motomura T, Inaba M, Fujio Y, Azuma J. Source: Diabetes Care. 2003 February; 26(2): 547-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12547903
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Muller cell changes in human diabetic retinopathy. Author(s): Mizutani M, Gerhardinger C, Lorenzi M. Source: Diabetes. 1998 March; 47(3): 445-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9519752
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Multifocal electroretinogram delays predict sites of subsequent diabetic retinopathy. Author(s): Han Y, Bearse MA Jr, Schneck ME, Barez S, Jacobsen CH, Adams AJ. Source: Investigative Ophthalmology & Visual Science. 2004 March; 45(3): 948-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14985316
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National screening for diabetic retinopathy: clear vision needed. Author(s): Mason J. Source: Diabetic Medicine : a Journal of the British Diabetic Association. 2003 December; 20(12): 959-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14632695
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National screening programme for diabetic retinopathy. Staff are already available to do this job. Author(s): Broughton R. Source: Bmj (Clinical Research Ed.). 2001 October 27; 323(7319): 999. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12141321
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Neurotrophic factor receptors in epiretinal membranes after human diabetic retinopathy. Author(s): Harada T, Harada C, Mitamura Y, Akazawa C, Ohtsuka K, Ohno S, Takeuchi S, Wada K. Source: Diabetes Care. 2002 June; 25(6): 1060-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12032115
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NF-kappaB in epiretinal membranes after human diabetic retinopathy. Author(s): Mitamura Y, Harada T, Harada C, Ohtsuka K, Kotake S, Ohno S, Tanaka K, Takeuchi S, Wada K. Source: Diabetologia. 2003 May; 46(5): 699-703. Epub 2003 May 13. Erratum In: Diabetologia. 2003 October; 46(10): 1446. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12743697
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Nitric oxide and vascular endothelial growth factor concentrations are increased but not related in vitreous fluid of patients with proliferative diabetic retinopathy. Author(s): Hernandez C, Lecube A, Segura RM, Sararols L, Simo R. Source: Diabetic Medicine : a Journal of the British Diabetic Association. 2002 August; 19(8): 655-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12147146
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No association between the MTHFR gene polymorphism and diabetic retinopathy in type 2 diabetic patients without overt nephropathy. Author(s): Yoshioka K, Yoshida T, Takakura Y, Kogure A, Umekawa T, Toda H, Yoshikawa T. Source: Diabetes Care. 2003 June; 26(6): 1947-8; Author Reply 1948. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12766148
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Non-stereo fundus photography as a screening procedure for diabetic retinopathy among patients with type II diabetes. Compared with 60D enhanced slit-lamp examination. Author(s): Kalm H, Egertsen R, Blohme G. Source: Acta Ophthalmol (Copenh). 1989 October; 67(5): 546-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2589054
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Non-stereo photographic screening after panretinal photocoagulation for proliferative diabetic retinopathy. Compared with 60D enhanced slit-lamp examination. Author(s): Kalm H, Sjodell L, Jonsson R. Source: Acta Ophthalmol (Copenh). 1989 October; 67(5): 554-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2589055
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Novel diagnostic and therapeutic approaches to the diabetic retinopathy. Author(s): Giusti C. Source: Eur Rev Med Pharmacol Sci. 2001 September-December; 5(5-6): 155-66. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12201666
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Occurrence and progression of diabetic retinopathy after phacoemulsification cataract surgery. Author(s): Hauser D, Katz H, Pokroy R, Bukelman A, Shechtman E, Pollack A. Source: Journal of Cataract and Refractive Surgery. 2004 February; 30(2): 428-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15030836
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Octreotide reduces vitreous hemorrhage and loss of visual acuity risk in patients with high-risk proliferative diabetic retinopathy. Author(s): Boehm BO, Lang GK, Jehle PM, Feldman B, Lang GE. Source: Hormone and Metabolic Research. Hormon- Und Stoffwechselforschung. Hormones Et Metabolisme. 2001 May; 33(5): 300-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11440277
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Ocular blood flow and associated functional deviations in diabetic retinopathy. Author(s): Schmetterer L, Wolzt M. Source: Diabetologia. 1999 April; 42(4): 387-405. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10230642
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Ocular blood flow parameters after pars plana vitrectomy in patients with diabetic retinopathy. Author(s): Krepler K, Polska E, Wedrich A, Schmetterer L. Source: Retina (Philadelphia, Pa.). 2003 April; 23(2): 192-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12707598
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Ocular blood flow velocities in patients with proliferative diabetic retinopathy after panretinal photocoagulation. Author(s): Mendivil A. Source: Survey of Ophthalmology. 1997 November; 42 Suppl 1: S89-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9603294
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Oncofetal fibronectin in diabetic retinopathy. Author(s): Khan ZA, Cukiernik M, Gonder JR, Chakrabarti S. Source: Investigative Ophthalmology & Visual Science. 2004 January; 45(1): 287-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14691186
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One-year outcomes of panretinal photocoagulation in proliferative diabetic retinopathy. Author(s): Kaiser RS, Maguire MG, Grunwald JE, Lieb D, Jani B, Brucker AJ, Maguire AM, Ho AC, Fine SL. Source: American Journal of Ophthalmology. 2000 February; 129(2): 178-85. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10682970
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Ophthaproblem. Diabetic retinopathy. Author(s): Sharma S. Source: Can Fam Physician. 1999 February; 45: 295, 304. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10065299
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Optical coherence tomography of tractional macular elevations in eyes with proliferative diabetic retinopathy. Author(s): Imai M, Iijima H, Hanada N. Source: American Journal of Ophthalmology. 2001 September; 132(3): 458-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11530091
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Optical coherence tomography of tractional macular elevations in eyes with proliferative diabetic retinopathy. Author(s): Imai M, Iijima H, Hanada N. Source: American Journal of Ophthalmology. 2001 July; 132(1): 81-4. Corrected and Republished In: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11438058
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Pathogenesis of diabetic retinopathy and the renin-angiotensin system. Author(s): Funatsu H, Yamashita H. Source: Ophthalmic & Physiological Optics : the Journal of the British College of Ophthalmic Opticians (Optometrists). 2003 November; 23(6): 495-501. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14622351
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Perspectives on diabetic retinopathy. Author(s): Polak BC, Dekker JM, Moll AC, Van Leiden HA. Source: American Journal of Ophthalmology. 2003 December; 136(6): 1193; Author Reply 1193. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14644255
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Pharmacologic therapy for diabetic retinopathy. Author(s): Speicher MA, Danis RP, Criswell M, Pratt L. Source: Expert Opinion on Emerging Drugs. 2003 May; 8(1): 239-50. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14610924
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Platelet activation in patients with diabetic retinopathy. Author(s): Bae SH, Lee J, Roh KH, Kim J. Source: Korean J Ophthalmol. 2003 December; 17(2): 140-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14717493
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Polymorphisms of sorbitol dehydrogenase (SDH) gene and susceptibility to diabetic retinopathy. Author(s): Amano S, Yamagishi S, Koda Y, Tsuneoka M, Soejima M, Okamoto T, Inagaki Y, Yamada K, Kimura H. Source: Medical Hypotheses. 2003 April; 60(4): 550-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12615520
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Potential new strategies to prevent the development of diabetic retinopathy. Author(s): Mohr S. Source: Expert Opinion on Investigational Drugs. 2004 March; 13(3): 189-98. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15013939
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Prevalence and determinants of diabetic retinopathy and cataracts in West African type 2 diabetes patients. Author(s): Rotimi C, Daniel H, Zhou J, Obisesan A, Chen G, Chen Y, Amoah A, Opoku V, Acheampong J, Agyenim-Boateng K, Eghan BA Jr, Oli J, Okafor G, Ofoegbu E, Osotimehin B, Abbiyesuku F, Johnson T, Fasanmade O, Doumatey A, Aje T, Collins F, Dunston G. Source: Ethn Dis. 2003 Summer; 13(2 Suppl 2): S110-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=13677425
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Prevalence of diabetic retinopathy in an Aboriginal Australian population: results from the Katherine Region Diabetic Retinopathy Study (KRDRS). Report no. 1. Author(s): Jaross N, Ryan P, Newland H. Source: Clinical & Experimental Ophthalmology. 2003 February; 31(1): 32-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12580891
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Progression of diabetic retinopathy after phacoemulsification in diabetic patients: a three-year analysis. Author(s): Liao SB, Ku WC. Source: Chang Gung Med J. 2003 November; 26(11): 829-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14765753
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Protein kinase C inhibition and diabetic retinopathy: a shot in the dark at translational research. Author(s): Donnelly R, Idris I, Forrester JV. Source: The British Journal of Ophthalmology. 2004 January; 88(1): 145-51. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14693793
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Quality assurance in screening for sight-threatening diabetic retinopathy. Author(s): Pandit RJ, Taylor R. Source: Diabetic Medicine : a Journal of the British Diabetic Association. 2002 April; 19(4): 285-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11942999
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Quality of life with visual acuity loss from diabetic retinopathy and age-related macular degeneration. Author(s): Brown MM, Brown GC, Sharma S, Landy J, Bakal J. Source: Archives of Ophthalmology. 2002 April; 120(4): 481-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11934322
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Quantifying alterations of macular thickness before and after panretinal photocoagulation in patients with severe diabetic retinopathy and good vision. Author(s): Shimura M, Yasuda K, Nakazawa T, Kano T, Ohta S, Tamai M. Source: Ophthalmology. 2003 December; 110(12): 2386-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14644723
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Quantitation of retinal ablation in proliferative diabetic retinopathy. Author(s): Reddy VM, Zamora RL, Olk RJ. Source: American Journal of Ophthalmology. 1995 June; 119(6): 760-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7785691
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Quantitative analysis of foveal retinal thickness in diabetic retinopathy with the scanning retinal thickness analyzer. Author(s): Yasukawa T, Kiryu J, Tsujikawa A, Dong J, Suzuma I, Takagi H, Ogura Y. Source: Retina (Philadelphia, Pa.). 1998; 18(2): 150-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9564696
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Quantitative assessment of macular thickness in normal subjects and patients with diabetic retinopathy by scanning retinal thickness analyser. Author(s): Oshima Y, Emi K, Yamanishi S, Motokura M. Source: The British Journal of Ophthalmology. 1999 January; 83(1): 54-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10209436
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Quantitative measurement of aqueous flare and aqueous "cells" in eyes with diabetic retinopathy. Author(s): Kuchle M, Schonherr U, Nguyen NX, Steinhauser B, Naumann GO. Source: Ger J Ophthalmol. 1992; 1(3-4): 164-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1483130
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Regulation of angiogenesis in diabetic retinopathy: possible balance between vascular endothelial growth factor and endostatin. Author(s): Noma H, Funatsu H, Yamashita H, Kitano S, Mishima HK, Hori S. Source: Archives of Ophthalmology. 2002 August; 120(8): 1075-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12149062
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Relationship between glycoxidation and cytokines in the vitreous of eyes with diabetic retinopathy. Author(s): Matsumoto Y, Takahashi M, Ogata M. Source: Japanese Journal of Ophthalmology. 2002 July-August; 46(4): 406-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12225819
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Reliability of the electronic early treatment diabetic retinopathy study testing protocol in children 7 to <13 years old. Author(s): Cotter SA, Chu RH, Chandler DL, Beck RW, Holmes JM, Rice ML, Hertle RW, Birch EE, Moke PS. Source: American Journal of Ophthalmology. 2003 October; 136(4): 655-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14516805
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Renin-angiotensin system in proliferative diabetic retinopathy and its gene expression in cultured human muller cells. Author(s): Kida T, Ikeda T, Nishimura M, Sugiyama T, Imamura Y, Sotozono C, Nishida K, Kinoshita S, Yoshimura M, Nakamura K, Inokuchi N. Source: Japanese Journal of Ophthalmology. 2003 January-February; 47(1): 36-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12586176
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Repeatability of an automated Landolt C test, compared with the early treatment of diabetic retinopathy study (ETDRS) chart testing. Author(s): Ruamviboonsuk P, Tiensuwan M, Kunawut C, Masayaanon P. Source: American Journal of Ophthalmology. 2003 October; 136(4): 662-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14516806
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Retinal vascular abnormalities in persons with type 1 diabetes: the Wisconsin Epidemiologic Study of Diabetic Retinopathy: XVIII. Author(s): Klein R, Klein BE, Moss SE, Wong TY, Hubbard L, Cruickshanks KJ, Palta M. Source: Ophthalmology. 2003 November; 110(11): 2118-25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14597518
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Reversion of 'early worsening' of diabetic retinopathy by deliberate restoration of poor metabolic control. Author(s): Chantelau E, Meyer-Schwickerath R. Source: Ophthalmologica. Journal International D'ophtalmologie. International Journal of Ophthalmology. Zeitschrift Fur Augenheilkunde. 2003 September-October; 217(5): 373-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12913330
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Risk factors for Type II diabetes and diabetic retinopathy in a mexican-american population: Proyecto VER. Author(s): West SK, Munoz B, Klein R, Broman AT, Sanchez R, Rodriguez J, Snyder R. Source: American Journal of Ophthalmology. 2002 September; 134(3): 390-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12208251
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Screening for diabetic retinopathy in James Bay, Ontario: a cost-effectiveness analysis. Author(s): Maberley D, Walker H, Koushik A, Cruess A. Source: Cmaj : Canadian Medical Association Journal = Journal De L'association Medicale Canadienne. 2003 January 21; 168(2): 160-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12538543
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Screening for diabetic retinopathy in remote Australia: a program description and evaluation of a devolved model. Author(s): Mak DB, Plant AJ, McAllister I. Source: The Australian Journal of Rural Health. 2003 October; 11(5): 224-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14641219
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Screening for diabetic retinopathy using the mobile retinal camera: the Waikato experience. Author(s): Reda E, Dunn P, Straker C, Worsley D, Gross K, Trapski I, Whitcombe S. Source: N Z Med J. 2003 August 22; 116(1180): U562. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14581984
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Screening for diabetic retinopathy, revisited. Author(s): Klein R, Klein BE. Source: American Journal of Ophthalmology. 2002 August; 134(2): 261-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12140033
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Screening for diabetic retinopathy: a cause for concern in people who drive. Author(s): Razvi S, Myers L, Patton K, McCulloch AJ. Source: Diabetic Medicine : a Journal of the British Diabetic Association. 2003 October; 20(10): 812-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14510861
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Screening for sight-threatening diabetic retinopathy: comparison of fundus photography with automated color contrast threshold test. Author(s): Ong GL, Ripley LG, Newsom RS, Cooper M, Casswell AG. Source: American Journal of Ophthalmology. 2004 March; 137(3): 445-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15013866
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Sensitivity and specificity of digital retinal images in grading diabetic retinopathy. Author(s): Saari JM, Summanen P, Kivela T, Saari KM. Source: Acta Ophthalmologica Scandinavica. 2004 April; 82(2): 126-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15043527
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Serum levels of glucose-derived advanced glycation end products are associated with the severity of diabetic retinopathy in type 2 diabetic patients without renal dysfunction. Author(s): Koga K, Yamagishi S, Okamoto T, Inagaki Y, Amano S, Takeuchi M, Makita Z. Source: Int J Clin Pharmacol Res. 2002; 22(1): 13-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12395914
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Severity of diabetic retinopathy is linked to lipoprotein (a) in type 1 diabetic patients. Author(s): Guerci B, Meyer L, Sommer S, George JL, Ziegler O, Drouin P, AngioiDuprez K. Source: Diabetes & Metabolism. 1999 November; 25(5): 412-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10592864
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Single-field fundus photography for diabetic retinopathy screening: a report by the American Academy of Ophthalmology. Author(s): Williams GA, Scott IU, Haller JA, Maguire AM, Marcus D, McDonald HR. Source: Ophthalmology. 2004 May; 111(5): 1055-62. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15121388
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The DIabetic Retinopathy Candesartan Trials (DIRECT) Programme, rationale and study design. Author(s): Chaturvedi N, Sjoelie AK, Svensson A; DIRECT Programme Study Group. Source: J Renin Angiotensin Aldosterone Syst. 2002 December; 3(4): 255-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12584669
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The impact of diabetic retinopathy on participation in daily living. Author(s): Lamoureux EL, Hassell JB, Keeffe JE. Source: Archives of Ophthalmology. 2004 January; 122(1): 84-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14718300
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The internist's role in managing diabetic retinopathy: screening for early detection. Author(s): Sinclair SH, Delvecchio C. Source: Cleve Clin J Med. 2004 February; 71(2): 151-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14982198
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The management of diabetic retinopathy. Author(s): Mathews JP, Mathews D, Lavin MJ. Source: The Practitioner. 2004 January; 248(1654): 34, 38-40, 42 Passim. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14997740
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The pathogenesis of diabetic retinopathy. Author(s): Stanford MR. Source: The British Journal of Ophthalmology. 2004 April; 88(4): 444-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15031149
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The potential role of PKC beta in diabetic retinopathy and macular edema. Author(s): Aiello LP. Source: Survey of Ophthalmology. 2002 December; 47 Suppl 2: S263-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12507628
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The prevalence of diabetic retinopathy among adult type 1 diabetic persons in the United States. Author(s): Roy MS, Klein R, O'Colmain BJ, Klein BE, Moss SE, Kempen JH. Source: Archives of Ophthalmology. 2004 April; 122(4): 546-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15078673
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The prevalence of diabetic retinopathy among adults in the United States. Author(s): Kempen JH, O'Colmain BJ, Leske MC, Haffner SM, Klein R, Moss SE, Taylor HR, Hamman RF; Eye Diseases Prevalence Research Group. Source: Archives of Ophthalmology. 2004 April; 122(4): 552-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15078674
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Three-year follow-up study of blood-retinal barrier and retinal thickness alterations in patients with type 2 diabetes mellitus and mild nonproliferative diabetic retinopathy. Author(s): Lobo CL, Bernardes RC, Figueira JP, de Abreu JR, Cunha-Vaz JG. Source: Archives of Ophthalmology. 2004 February; 122(2): 211-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14769598
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TTO utility scores measure quality of life in patients with visual morbidity due to diabetic retinopathy or ARMD. Author(s): Shah VA, Gupta SK, Shah KV, Vinjamaram S, Chalam KV. Source: Ophthalmic Epidemiology. 2004 February; 11(1): 43-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14977496
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Unbalanced vitreous levels of pigment epithelium-derived factor and vascular endothelial growth factor in diabetic retinopathy. Author(s): Ogata N, Nishikawa M, Nishimura T, Mitsuma Y, Matsumura M. Source: American Journal of Ophthalmology. 2002 September; 134(3): 348-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12208245
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Understanding the value of diabetic retinopathy screening. Author(s): Fong DS, Gottlieb J, Ferris FL 3rd, Klein R. Source: Archives of Ophthalmology. 2001 May; 119(5): 758-60. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11346406
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United Kingdom Prospective Diabetes Study, 30: diabetic retinopathy at diagnosis of non-insulin-dependent diabetes mellitus and associated risk factors. Author(s): Kohner EM, Aldington SJ, Stratton IM, Manley SE, Holman RR, Matthews DR, Turner RC. Source: Archives of Ophthalmology. 1998 March; 116(3): 297-303. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9514482
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Use of Joslin Vision Network digital-video nonmydriatic retinal imaging to assess diabetic retinopathy in a clinical program. Author(s): Cavallerano AA, Cavallerano JD, Katalinic P, Tolson AM, Aiello LP, Aiello LM; Joslin Vision Network Clinical Team. Source: Retina (Philadelphia, Pa.). 2003 April; 23(2): 215-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12707602
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Use of oral fluorescein angiography in the diagnosis of macular oedema within a diabetic retinopathy screening programme. Author(s): Razvi FM, Kritzinger EE, Tsaloumas MD, Ryder RE. Source: Diabetic Medicine : a Journal of the British Diabetic Association. 2001 December; 18(12): 1003-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11903401
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Use of perfluorocarbon liquid during vitrectomy for severe proliferative diabetic retinopathy. Author(s): Imamura Y, Minami M, Ueki M, Satoh B, Ikeda T. Source: The British Journal of Ophthalmology. 2003 May; 87(5): 563-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12714393
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Use of telemedicine in periodic screening of diabetic retinopathy. Author(s): Kawasaki S, Ito S, Satoh S, Mori Y, Saito T, Fukushima H, Kato S, Sekihara H. Source: Telemedicine Journal and E-Health : the Official Journal of the American Telemedicine Association. 2003 Fall; 9(3): 235-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14611690
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Use of telemedicine in screening for diabetic retinopathy. Author(s): Choremis J, Chow DR. Source: Can J Ophthalmol. 2003 December; 38(7): 575-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14740799
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Usefulness of corneal esthesiometry for screening diabetic retinopathy. Author(s): Alvarenga LS, Martins EN, Grottone GT, Morales PH, Paranhos A Jr, Freitas D, Scarpi MJ. Source: Revista De Saude Publica. 2003 October; 37(5): 609-15. Epub 2003 October 09. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14569337
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Utilities associated with diabetic retinopathy: results from a Canadian sample. Author(s): Sharma S, Oliver-Fernandez A, Bakal J, Hollands H, Brown GC, Brown MM. Source: The British Journal of Ophthalmology. 2003 March; 87(3): 259-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12598432
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Vascular endothelial growth factor and severity of nonproliferative diabetic retinopathy mediate retinal hemodynamics in vivo: a potential role for vascular endothelial growth factor in the progression of nonproliferative diabetic retinopathy. Author(s): Clermont AC, Aiello LP, Mori F, Aiello LM, Bursell SE. Source: American Journal of Ophthalmology. 1997 October; 124(4): 433-46. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9323935
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Vascular endothelial growth factor gene regulation and action in diabetic retinopathy. Author(s): Lu M, Adamis AP. Source: Ophthalmology Clinics of North America. 2002 March; 15(1): 69-79. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12064083
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Vision after photocoagulation for diabetic retinopathy. Author(s): Colucciello M. Source: Postgraduate Medicine. 1998 May; 103(5): 37-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9590985
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Vitrectomy for complications of diabetic retinopathy. Author(s): Smiddy WE. Source: International Ophthalmology Clinics. 1998 Spring; 38(2): 155-67. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9604743
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Vitrectomy for traction macular detachment in diabetic retinopathy. Author(s): Meier P, Wiedemann P. Source: Graefe's Archive for Clinical and Experimental Ophthalmology = Albrecht Von Graefes Archiv Fur Klinische Und Experimentelle Ophthalmologie. 1997 September; 235(9): 569-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9342607
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Vitrectomy with silicone oil infusion in severe diabetic retinopathy. Author(s): Castellarin A, Grigorian R, Bhagat N, Del Priore L, Zarbin MA. Source: The British Journal of Ophthalmology. 2003 March; 87(3): 318-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12598446
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Vitreous hemorrhage after closed vitrectomy for proliferative diabetic retinopathy. Author(s): Tolentino FI, Cajita VN, Gancayco T, Skates S. Source: Ophthalmology. 1989 October; 96(10): 1495-500. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2587044
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Vitreous levels of insulin-like growth factor-I in patients with proliferative diabetic retinopathy. Author(s): Inokuchi N, Ikeda T, Imamura Y, Sotozono C, Kinoshita S, Uchihori Y, Nakamura K. Source: Current Eye Research. 2001 November; 23(5): 368-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11910526
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Vitreous levels of placenta growth factor and vascular endothelial growth factor in patients with proliferative diabetic retinopathy. Author(s): Mitamura Y, Tashimo A, Nakamura Y, Tagawa H, Ohtsuka K, Mizue Y, Nishihira J. Source: Diabetes Care. 2002 December; 25(12): 2352. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12453985
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Vitreous levels of vascular endothelial growth factor are not influenced by its serum concentrations in diabetic retinopathy. Author(s): Burgos R, Simo R, Audi L, Mateo C, Mesa J, Garcia-Ramirez M, Carrascosa A. Source: Diabetologia. 1997 September; 40(9): 1107-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9300249
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What may be gained from standard photocoagulation during early worsening of diabetic retinopathy? An observational study in type-1 diabetic patients after tightening of glycaemic control. Author(s): Am J Ophthalmol. 2001 Sep;132(3):458-61 Source: Diabetes & Metabolism. 2001 June; 27(3): 366-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11530091
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What you need to know about diabetic retinopathy. Author(s): Smith CW, Feldman JP. Source: R I Med J. 1991 October; 74(10): 459-62. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1957114
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What you should know about diabetic retinopathy. Author(s): Roach VG. Source: J Ophthalmic Nurs Technol. 1988 September-October; 7(5): 166-9. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3418723
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When does neural degeneration occur in diabetic retinopathy? Author(s): Gillies M. Source: Clinical & Experimental Ophthalmology. 2000 February; 28(1): 1-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11345336
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Who should treat diabetic retinopathy? Author(s): Gregor ZJ. Source: Eye (London, England). 1988; 2 ( Pt 4): Vii. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3253127
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Wisconsin Epidemiologic Study of Diabetic Retinopathy. XII. Relationship of Cpeptide and diabetic retinopathy. Author(s): Klein R, Moss SE, Klein BE, Davis MD, DeMets DL. Source: Diabetes. 1990 November; 39(11): 1445-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2121570
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Wolfram (DIDMOAD) syndrome with diabetic retinopathy. Author(s): Gupta KL, Ghosh AK, Jha V, Gupta A, Sakhuja V. Source: J Assoc Physicians India. 1994 October; 42(10): 831-2. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7876060
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Worsening of diabetic retinopathy after improvement of glycemic control. Author(s): Davis MD. Source: Archives of Ophthalmology. 1998 July; 116(7): 931-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9682709
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Z-2 aldose reductase allele and diabetic retinopathy in India. Author(s): Kumaramanickavel G, Sripriya S, Ramprasad VL, Upadyay NK, Paul PG, Sharma T. Source: Ophthalmic Genetics. 2003 March; 24(1): 41-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12660865
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CHAPTER 2. NUTRITION AND DIABETIC RETINOPATHY Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and diabetic retinopathy.
Finding Nutrition Studies on Diabetic Retinopathy 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 “diabetic retinopathy” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.
7 Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.
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The following is a typical result when searching for recently indexed consumer information on diabetic retinopathy: •
Fibrinolysis and diabetic retinopathy in NIDDM. Author(s): Division of Medicine, University of Leeds, U.K.
[email protected] Source: Mansfield, M W Grant, P J Diabetes-Care. 1995 December; 18(12): 1577-81 01495992
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Is the risk of diabetic retinopathy greater in non-Hispanic blacks and Mexican Americans than in non-Hispanic whites with type 2 diabetes? A U.S. population study. Author(s): National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, USA.
[email protected] Source: Harris, M I Klein, R Cowie, C C Rowland, M Byrd Holt, D D Diabetes-Care. 1998 August; 21(8): 1230-5 0149-5992
The following information is typical of that found when using the “Full IBIDS Database” to search for “diabetic retinopathy” (or a synonym): •
Correlation between progression of diabetic retinopathy and blood glucose control. Author(s): Department of Diabetic Ophthalmology, Tokyo Women's Medical College, Japan. Source: Funatsu, H Yamashita, H Ohashi, Y Ishigaki, T Jpn-J-Ophthalmol. 1991; 35(3): 306-16 0021-5155
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Effect of near normoglycemia for 5 years on progression of early diabetic retinopathy and renal involvement. Author(s): Medical Endocrinological Department III, Aarhus County Hospital, Denmark. Source: Beck Nielsen, H Olesen, T Mogensen, C E Richelsen, B Olsen, H W Ehlers, N Charles, P Sorensen, N S Diabetes-Res. 1990 December; 15(4): 185-90 0265-5985
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Is diabetic retinopathy preventable? Author(s): Department of Ophthalmology, University of Wisconsin School of Medicine, Madison 53706. Source: Engerman, R L Kern, T S Int-Ophthalmol-Clin. 1987 Winter; 27(4): 225-9 00208167
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Microaneurysms in the development of diabetic retinopathy (UKPDS 42). UK Prospective Diabetes Study Group. Author(s): Department of Medicine St. Thomas' Hospital, London, UK. Source: Kohner, E M Stratton, I M Aldington, S J Turner, R C Matthews, D R Diabetologia. 1999 September; 42(9): 1107-12 0012-186X
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Prevalence of diabetic retinopathy and evaluation of risk factors. A review of 1,005 diabetic clinic patients. Author(s): Department of Ophthalmology, University of Stellenbosch and Tygerberg Hospital, Parowvallei, CP. Source: Mouton, D P Gill, A J S-Afr-Med-J. 1988 October 15; 74(8): 399-402 0038-2469
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Proliferative diabetic retinopathy in NIDDM and Indian diet. Source: Raheja, B Modi, K Barua, J Jain, S Shahani, V Koppikar, G J-Med-Assoc-Thai. 1987 March; 70 Suppl 2139-43 0125-2208
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The prevalence and risk of diabetic retinopathy among Indians of southwest Oklahoma. Source: Newell, S W Tolbert, B Bennett, J Parsley, T L J-Okla-State-Med-Assoc. 1989 August; 82(8): 414-24 0030-1876
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Time course of NADH oxidase, inducible nitric oxide synthase and peroxynitrite in diabetic retinopathy in the BBZ/WOR rat. Author(s): Department of Pharmacology and Therapeutics, College of Medicine, Gainesville, Florida 32610, USA. Source: Ellis, E A Guberski, D L Hutson, B Grant, M B Nitric-Oxide. 2002 May; 6(3): 295304 1089-8603
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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WebMDHealth: http://my.webmd.com/nutrition
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
The following is a specific Web list relating to diabetic retinopathy; 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 A Source: Healthnotes, Inc.; www.healthnotes.com Vitamin C Source: Healthnotes, Inc.; www.healthnotes.com Vitamin E Source: Healthnotes, Inc.; www.healthnotes.com
•
Minerals Selenium Source: Healthnotes, Inc.; www.healthnotes.com
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CHAPTER 3. ALTERNATIVE MEDICINE AND DIABETIC RETINOPATHY Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to diabetic retinopathy. 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 diabetic retinopathy 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 “diabetic retinopathy” (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 diabetic retinopathy: •
Acceleration of experimental diabetic retinopathy in the rat by omega-3 fatty acids. Author(s): Hammes HP, Weiss A, Fuhrer D, Kramer HJ, Papavassilis C, Grimminger F. Source: Diabetologia. 1996 March; 39(3): 251-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8721768
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Antioxidant nutrient intake and diabetic retinopathy: the San Luis Valley Diabetes Study. Author(s): Mayer-Davis EJ, Bell RA, Reboussin BA, Rushing J, Marshall JA, Hamman RF. Source: Ophthalmology. 1998 December; 105(12): 2264-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9855158
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Diabetic retinopathy and capillary resistance. Comparative study of various treatments. Author(s): Sevin R, Cuendet JF. Source: Bibl Ophthalmol. 1968; 76: 139-45. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5674834
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Diabetic retinopathy. Author(s): Kohner EM, Oakley NW. Source: Metabolism: Clinical and Experimental. 1975 September; 24(9): 1085-102. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1097858
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Diabetic retinopathy: study of the action of O-betahydroxyethyl-rutosides (HR) by retinal fluoresceinography. Author(s): Tschopp M, Pometta D, Babel J. Source: Diabetologia. 1970 October; 6(5): 475-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5474813
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Flavonoid therapy in diabetic retinopathy. Author(s): BRICKLEY PM, GIFFORD BL, DOMZ CA. Source: Calif Med. 1959 January; 90(1): 45-8. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=13618745
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Influence of different diets on the progression of diabetic retinopathy. Author(s): Houtsmuller AJ, van Hal-Ferwerda J, Zahn KJ, Henkes HE. Source: Prog Food Nutr Sci. 1980; 4(5): 41-6. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7005962
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National screening programme for diabetic retinopathy. Screening by retinal photography offers holistic package of diabetic care. Author(s): Prince CB. Source: Bmj (Clinical Research Ed.). 2002 April 6; 324(7341): 849; Author Reply 849-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11936161
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Nitric oxide deficiency, leukocyte activation, and resultant ischemia are crucial to the pathogenesis of diabetic retinopathy/neuropathy--preventive potential of antioxidants, essential fatty acids, chromium, ginkgolides, and pentoxifylline. Author(s): McCarty MF. Source: Medical Hypotheses. 1998 May; 50(5): 435-49. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9681924
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Nonproliferative diabetic retinopathy and macular edema. Author(s): Smith SC.
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Source: Insight (American Society of Ophthalmic Registered Nurses). 1999 April-June; 24(2): 59-62; Quiz 63-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11907881 •
Platelet abnormalities as related to diabetic retinopathy (with special reference to platelet shape change). Author(s): Porta M, O'Brien ME, Kohner EM. Source: Horm Metab Res Suppl. 1981; 11: 50-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6797912
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Polyunsaturated fatty acids and diabetic retinopathy. Author(s): Howard-Williams J, Patel P, Jelfs R, Carter RD, Awdry P, Bron A, Mann JI, Hockaday TD. Source: The British Journal of Ophthalmology. 1985 January; 69(1): 15-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3965024
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Pycnogenol for diabetic retinopathy. A review. Author(s): Schonlau F, Rohdewald P. Source: International Ophthalmology. 2001; 24(3): 161-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12498513
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Relation between intake of vitamins C and E and risk of diabetic retinopathy in the Atherosclerosis Risk in Communities Study. Author(s): Millen AE, Klein R, Folsom AR, Stevens J, Palta M, Mares JA. Source: The American Journal of Clinical Nutrition. 2004 May; 79(5): 865-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15113727
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Relations of serum ascorbic acid and alpha-tocopherol to diabetic retinopathy in the Third National Health and Nutrition Examination Survey. Author(s): Millen AE, Gruber M, Klein R, Klein BE, Palta M, Mares JA. Source: American Journal of Epidemiology. 2003 August 1; 158(3): 225-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12882944
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Unsaturated fats and progression of diabetic retinopathy. Author(s): Houtsmuller AJ, Zahn KJ, Henkes HE. Source: Documenta Ophthalmologica. Advances in Ophthalmology. 1980 April 15; 48(2): 363-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6995054
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Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: •
Alternative Medicine Foundation, Inc.: http://www.herbmed.org/
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AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats
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Chinese Medicine: http://www.newcenturynutrition.com/
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drkoop.com: http://www.drkoop.com/InteractiveMedicine/IndexC.html
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Family Village: http://www.familyvillage.wisc.edu/med_altn.htm
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Google: http://directory.google.com/Top/Health/Alternative/
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Healthnotes: http://www.healthnotes.com/
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MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine
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Open Directory Project: http://dmoz.org/Health/Alternative/
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HealthGate: http://www.tnp.com/
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WebMDHealth: 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 diabetic retinopathy; 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 Diabetes Source: Healthnotes, Inc.; www.healthnotes.com Diabetes Source: Prima Communications, Inc.www.personalhealthzone.com Retinopathy Source: Healthnotes, Inc.; www.healthnotes.com
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Herbs and Supplements Bilberry Alternative names: Vaccinium myrtillus, European Blueberry, Huckleberry Source: Integrative Medicine Communications; www.drkoop.com Bilberry Source: Prima Communications, Inc.www.personalhealthzone.com
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Bilberry Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10007,00.html European Blueberry Source: Integrative Medicine Communications; www.drkoop.com Ginkgo Biloba Source: Healthnotes, Inc.; www.healthnotes.com Ginkgo Biloba Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,788,00.html Huckleberry Source: Integrative Medicine Communications; www.drkoop.com OPCS (Oligomeric Proanthocyanidins) Source: Prima Communications, Inc.www.personalhealthzone.com Vaccinium Myrtillus Source: Integrative Medicine Communications; www.drkoop.com
General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the MEDLINEplus site at http://www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources.
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CHAPTER 4. DISSERTATIONS ON DIABETIC RETINOPATHY Overview In this chapter, we will give you a bibliography on recent dissertations relating to diabetic retinopathy. 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 “diabetic retinopathy” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on diabetic retinopathy, we have not necessarily excluded non-medical dissertations in this bibliography.
Dissertations on Diabetic Retinopathy 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 diabetic retinopathy. 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: •
Medical imaging: Requirements analysis for automating diabetic retinopathy monitoring and diagnosis by Kornechuk, Thomas Daniel, MCSc from DALHOUSIE UNIVERSITY (CANADA), 2003, 89 pages http://wwwlib.umi.com/dissertations/fullcit/MQ79534
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. PATENTS ON DIABETIC RETINOPATHY Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.8 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “diabetic retinopathy” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on diabetic retinopathy, we have not necessarily excluded non-medical patents in this bibliography.
Patents on Diabetic Retinopathy By performing a patent search focusing on diabetic retinopathy, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We will tell you how to obtain this information later in the chapter. 8Adapted
from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.
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The following is an example of the type of information that you can expect to obtain from a patent search on diabetic retinopathy: •
Apparatus for measuring the autofluorescence of the cornea of an eye Inventor(s): Docchio; Franco (Brescia, IT), van Best; Jasper Anton (Leiden, NL) Assignee(s): Leiden University (Medical Center) (Leiden, NL) Patent Number: 6,611,704 Date filed: July 27, 2000 Abstract: For the early detection of blindness-causing diabetic retinopathy, an apparatus for measuring the autofluorescence of the cornea of an eye, comprising means for tangentially illuminating the cornea, means for receiving the autofluorescent radiation generated in the cornea by this illumination, and means for processing the measured autofluorescent radiation, wherein the means for tangentially illuminating the cornea comprises at least one light source which radiates blue light and at least one filter which transmits at least a part of the blue light in a light path to the cornea, and the means for receiving the autofluorescent radiation generated in the cornea comprises at least one filter which transmits green light. Excerpt(s): This invention relates to an apparatus for measuring the autofluorescence of the cornea of an eye, comprising means for substantially tangentially illuminating the cornea, means for receiving the autofluorescent radiation generated in the cornea by this illumination, and means for processing the measured autofluorescent radiation. Such an apparatus is known from Italian patent application IT-94.501.069. Apparatuses for measuring the autofluorescent radiation of the cornea of an eye are used in screening diabetes patients for diabetic retinopathy. Diabetic retinopathy is one of the moat important causes of blindness in the Western world and its timely detection can contribute to delaying or even preventing blindness in patients by administering laser therapy. Recent studies have shown that the autofluorescence of the corneal tissue in certain wavelength regions increases considerably with the severity of diabetic retinopathy. By other conventional methods, diabetic retinopathy and its progression are difficult to detect. The advantage of measuring corneal autofluorescence is that the cornea is readily accessible for examination and that the amount of corneal autofluorescence is not or only slightly age-dependent. Web site: http://www.delphion.com/details?pn=US06611704__
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Compositions and treatment for diabetic complications Inventor(s): Mylari; Banavara L. (Waterford, CT) Assignee(s): Pfizer Inc. (New York, NY) Patent Number: 6,413,965 Date filed: June 23, 2000 Abstract: This invention is directed to methods, pharmaceutical compositions and kits comprising an aldose reductase inhibitor (ARI), a prodrug thereof or a pharmaceutically acceptable salt of said ARI or said prodrug and a selective COX-2 inhibitor, a prodrug thereof or a pharmaceutically acceptable salt of said selective COX-2 inhibitor or said prodrug. This invention further relates to methods of using those pharmaceutical
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compositions for the treatment of diabetic complications such as diabetic neuropathy, diabetic nephropathy, diabetic retinopathy and diabetic cardiomyopathy. Excerpt(s): This invention relates to methods, pharmaceutical compositions and kits comprising an aldose reductase inhibitor (ARI), a prodrug thereof or a pharmaceutically acceptable salt of said ARI or said prodrug and a selective cyclooxygenase-2 (COX-2) inhibitor, a prodrug thereof or a pharmaceutically acceptable salt of said selective COX2 inhibitor or said prodrug. This invention further relates to methods of using such pharmaceutical compositions for the treatment of diabetic complications such as diabetic neuropathy, diabetic nephropathy, diabetic retinopathy, myocardial infarction, cataracts and diabetic cardiomyopathy. Aldose reductase inhibitors function by inhibiting the activity of the enzyme aldose reductase, which is primarily responsible for regulating the reduction of aldoses, such as glucose and galactose, to the corresponding polyols, such as sorbitol and galactitol, in humans and other animals. In this way, unwanted accumulations of galactitol in the lens of galactosemic subjects and of sorbitol in the lens, peripheral nervous cord and kidneys of various diabetic subjects are prevented or reduced. Accordingly, aldose reductase inhibitors are of therapeutic value for controlling certain diabetic complications, e.g., diabetic neuropathy, diabetic nephropathy, diabetic cardiomyopathy, myocardial infarction, cataracts and diabetic retinopathy. Two forms of cylcooxygenase (COX) are known to exist: COX-1 and COX2, the former being a constitutive form and the latter being an inducible form. COX-1 exists in the stomach, intestines, kidneys and platelets while COX-2 is expressed during inflammation. Both COX enzyme isoforms metabolize arachidonic by a similar mechanism, but each have different substrate specificities. Selective COX-2 inhibitors are advantageous in the treatment of pain and inflammation while avoiding such side effects as gastric and renal toxicity. Web site: http://www.delphion.com/details?pn=US06413965__ •
Detecting genetic predisposition to sight-threatening diabetic retinopathy Inventor(s): Duff; Gordon W. (South Yorkshire, GB), Rennie; Ian G. (Newbold, GB), Richardson; Patrick R. S. (Litton Nr. Buxton, GB) Assignee(s): Interleukin Genetics, Inc. (Waltham, MA) Patent Number: 6,713,253 Date filed: March 10, 1998 Abstract: A method and kit for predicting increased risk of sight-threatening diabetic retinopathy which includes isolating genomic DNA from a sample from a diabetic patient. The genetic polymorphism pattern for the genes IL-1A, IL-1B and IL-1RN is then identified in the DNA. The identified pattern is compared with control patterns of known polymorphisms, and patients expressing a genetic polymorphism pattern associated with increased risk of sight-threatening diabetic retinopathy are identified. Excerpt(s): This application is the national phase of PCT Patent Application GB97/02790 filed on Oct. 9, 1997; which claims priority to UK Provisional Application No. GB 9621129.7, filed on Oct. 10, 1996. This invention relates to a method of detecting a predisposition to, and determining risk of, sight-threatening diabetic retinopathy. The invention also provides diagnostic kits for the assessment of risk of developing sightthreatening diabetic retinopathy. Insulin dependent (Type I) and non-insulin dependent (Type II) diabetes mellitus are distinct diseases and patients with either form of the disease are at risk of developing microvascular and macrovascular complications
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such as neuropathy, nephropathy, retinopathy, atherosclerosis and cardiovascular disease. These complications are a major clinical burden in diabetes, but their pathogenesis is not well understood. Susceptibility to diabetic complications has been reported to be inherited independently of diabetes itself. [Seaquist et al., 1989; Ko et al., 1995]. Web site: http://www.delphion.com/details?pn=US06713253__ •
Vascular endothelial growth factor 2 proteins and compositions Inventor(s): Cao; Liang (Bethesda, MD), Hu; Jing-Shan (Mountain View, CA), Rosen; Craig A. (Laytonsville, MD) Assignee(s): Human Genome Sciences, Inc. (Rockville, MD) Patent Number: 6,734,285 Date filed: February 28, 2002 Abstract: Disclosed are human VEGF-2 polypeptides, biologically active, diagnostically or therapeutically useful fragments, analogs, or derivatives thereof, and DNA(RNA) encoding such VEGF-2 polypeptides. Also provided are procedures for producing such polypeptides by recombinant techniques and antibodies and antagonists against such polypeptides. Such polypeptides and polynucleotides may be used therapeutically for stimulating wound healing and for vascular tissue repair. Also provided are methods of using the antibodies and antagonists to inhibit tumor angiogenesis and thus tumor growth, inflammation, diabetic retinopathy, rheumatoid arthritis, and psoriasis. Excerpt(s): The present invention relates to newly identified polynucleotides, polypeptides encoded by such polynucleotides, the use of such polynucleotides and polypeptides, as well as the production of such polynucleotides and polypeptides. The polypeptides of the present invention have been identified as members of the vascular endothelial growth factor family. More particularly, the polypeptides of the present invention are human vascular endothelial growth factor 2 (VEGF-2). The invention also relates to inhibiting the action of such polypeptides. The formation of new blood vessels, or angiogenesis, is essential for embryonic development, subsequent growth, and tissue repair. Angiogenesis is also an essential part of certain pathological conditions, such as neoplasia (i.e., tumors and gliomas). Abnormal angiogenesis is associated with other diseases such as inflammation, rheumatoid arthritis, psoriasis, and diabetic retinopathy (Folkman, J. and Klagsbrun, M., Science 235:442-447(1987)). Both acidic and basic fibroblast growth factor molecules are mitogens for endothelial cells and other cell types. Angiotropin and angiogenin can induce angiogenesis, although their functions are unclear (Folkman, J., Cancer Medicine, Lea and Febiger Press, pp. 153-170 (1993)). A highly selective mitogen for vascular endothelial cells is vascular endothelial growth factor or VEGF (Ferrara, N. et al., Endocr. Rev. 13:19-32 (1992)), which is also known as vascular permeability factor (VPF). Web site: http://www.delphion.com/details?pn=US06734285__
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Patent Applications on Diabetic Retinopathy As of December 2000, U.S. patent applications are open to public viewing.9 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to diabetic retinopathy: •
Compositions and methods for treatment of angiogenesis in pathological lesions Inventor(s): Borsi, Laura; (Genova, IT), Carnemolla, Barbara; (Genova, IT), Halin, Cornelia; (Zurich, CH), Neri, Dario; (Zurich, CH), Nilsson, Fredrik; (Stockholm, SE), Tarli, Lorenzo; (Siena, IT), Zardi, Luciano; (Genova, IT) Correspondence: Dann, Dorfman, Herrell & Skillman; 1601 Market Street; Suite 2400; Philadelphia; PA; 19103-2307; US Patent Application Number: 20040013640 Date filed: March 10, 2003 Abstract: Treatment of lesions of pathological angiogenesis, especially tumors, rheumatoid arthritis, diabetic retinopathy, age-related muscular degeneration. and angiomas. A conjugate is used comprising a molecule that exerts a biocidal or cytotoxic effect on target cells in the lesions and an antibody directed against an extracellular matrix component which is present in such lesions. The antibody may be directed against fibronectin-2 (IL-2), doxorubicin, interleukin-12(IL-12), Interferon-.gamma. (IFN.gamma.), Tumor Necrosis Factor.alpha.(TNF.alpha.) or Tissue Factor protein (which may be truncated). Excerpt(s): The present invention relates to treatment of lesions of pathological angiogenesis, especially tumors, rheumatoid arthritis, diabetic retinopathy, age-related macular degeneration, and angiomas. Aspects of the present invention employ a conjugate or fusion of a molecule that exerts a biocidal or cytotoxic effect on target cells in the lesions and an antibody directed against an extracellular matrix component which is present in such lesions. In preferred embodiments, the antibody is directed against fibronectin ED-B. Preferred embodiments of the biocidal or cytotoxic molecule include interleukin-2 (IL-2), doxorubicin, interleukin-12 (IL-12), Interferon-.gamma. (IFN.gamma.), Tumor Necrosis Factor.alpha. (TNF.alpha.) also, especially with the L19 antibody (see below), tissue factor (preferably truncated). By targeting bioactive molecules to an extracellular matrix component, killing of target cells may be achieved. Tumors cannot grow beyond a certain mass without the formation of new blood vessels (angiogenesis), and a correlation between microvessel density and tumor invasiveness has been reported for a number of tumors (1). Molecules capable of selectively targeting markers of angiogenesis create clinical opportunities for the diagnosis and therapy of tumors and other diseases characterized by vascular proliferation, such as rheumatoid arthritis, diabetic retinopathy and age-related macular degeneration (2-8). The ED-B domain of fibronectin, a sequence of 91 amino acids identical in mice, rats and humans, which is inserted by alternative splicing into the fibronectin molecule, specifically accumulates around neovascular structures and represents a target for molecular intervention (9-11). Using a human recombinant antibody (L19) to the ED-B domain the possibility of in vivo neovasculature targeting has been demonstrated in different tumor models (12,13). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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This has been a common practice outside the United States prior to December 2000.
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Compounds and method for the prevention and treatment of diabetic retinopathy Inventor(s): Bodor, Nicholas Stephen; (Gainesville, FL), Grant, Maria; (Gainesville, FL) Correspondence: Van Dyke & Associates, P.A.; Suite 252; 7200 Lake Ellenor Drive; Orlando; FL; 32809; US Patent Application Number: 20040082501 Date filed: April 11, 2003 Abstract: The invention provides peptide derivatives designed to deliver peptides having growth factor inhibitory activity, especially somatostatin analogs, to the retina by sequential metabolism. The peptide derivatives, which comprise a dihydropyridinepyridinium salt-type redox targetor moiety, a bulky lipophilic function and an amino acid/dipeptide/tripeptid- e spacer, are used in the prevention and treatment of diabetic retinopathy. Excerpt(s): This application is a continuation of U.S. application Ser. No. 10/175,833 filed Jun. 21, 2001, pending, which is a divisional of U.S. application Ser. No. 09/144,991, filed Sep. 1, 1998, now issued as U.S. Pat. No. 6,440,933 on Aug. 27, 2002, which claims the priority of U.S. Provisional Patent Application No. 60/058,423, filed Sep. 10, 1997. Priority is claimed to the foregoing applications and are incorporated by reference herein in their entirety and relied upon. The invention relates to peptide derivatives designed to deliver peptides having growth factor inhibitory activity into the retina by sequential metabolism. These peptide derivatives, which comprise a dihydropyridinepyridinium salt-type redox targetor moiety, a bulky lipophilic function and an amino acid/dipeptide/tripeptide spacer, are of use in the prevention and treatment of diabetic retinopathy. The leading cause of blindness in adults between the ages of 20 and 74 years is diabetic retinopathy (DR). Seven million people in the United States have diabetes. Diabetic retinopathy will affect the vast majority during their lifetime, with 8,000 to 40,000 of these people becoming blind each year. While management of diabetic retinopathy has improved as a result of landmark clinical trials, risk of complications, such as loss of visual acuity, loss of night vision and loss of peripheral vision, remains significant and treatment sometimes fails. Currently, laser photocoagulation is the most effective form of therapy for advanced disease. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Integrin expression inhibitors Inventor(s): Funahashi, Yasuhiro; (Ibaraki, JP), Hamaoka, Shinichi; (Ibaraki, JP), Haneda, Toru; (Ibaraki, JP), Hata, Naoko; (Ibaraki, JP), Kamata, Junichi; (Ibaraki, JP), Nara, Kazumasa; (Ibaraki, JP), Okabe, Tadashi; (Ibaraki, JP), Owa, Takashi; (Ibaraki, JP), Semba, Taro; (Ibaraki, JP), Takahashi, Keiko; (Ibaraki, JP), Tsuruoka, Akihiko; (Ibaraki, JP), Ueda, Norihiro; (Ibaraki, JP), Wakabayashi, Toshiaki; (Ibaraki, JP), Yamamoto, Yuji; (Ibaraki, JP) Correspondence: Birch Stewart Kolasch & Birch; PO Box 747; Falls Church; VA; 220400747; US Patent Application Number: 20040018192 Date filed: July 18, 2002 Abstract: The present invention provides an integrin expression inhibitor, and an agent for treating arterial sclerosis, psoriasis, cancer, retinal angiogenesis, diabetic retinopathy
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or inflammatory diseases, an anticoagulant, or a cancer metastasis suppressor on the basis of an integrin inhibitory action. Namely, it provides an integrin expression inhibitor comprising, as an active ingredient, a sulfonamide compound represented by the following formula (I), a pharmacologically acceptable salt thereof or a hydrate of them. 1In the formula, B means a C6-C10 aryl ring or 6- to 10-membered heteroaryl ring which may have a substituent and in which a part of the ring may be saturated; K means a single bond, --CH.dbd.CH-- or --(CR.sup.4bR.sup.5b).sub.m.sup.b-- (wherein R.sup.4b and R.sup.5b are the same as or different from each other and each means hydrogen atom or a C1-C4 alkyl group; and m.sup.b means an integer of 1 or 2); R.sup.1 means hydrogen atom or a C1-C6 alkyl group; Z means a single bond or --CO--NH--; and R means a C6-C10 aryl ring or 6- to 10-membered heteroaryl ring which may have a substituent and in which a part of the ring may be saturated, respectively. Excerpt(s): The present invention relates to an integrin expression inhibitor, specifically, an integrin.alpha.2.beta.1,.alpha.3.beta.1,.alpha.5.beta.1,.alpha.6.beta.1,.alpha.v.sym.1,.alph a.v.beta.3 or.alpha.v.beta.5 expression inhibitor. Further it relates to an angiogenesis agent, an anticoagulant, an anticancer agent, a cancer metastasis suppressor, and an agent for treating retinal angiogenesis, diabetic retinopathy, inflammatory diseases, arterial sclerosis, psoriasis and osteoporosis, on the basis of integrin expression inhibitory action. Integrin structurally consists of a heterodimer in which two types of sub-unit, namely, integrin.alpha. and integrin.beta. are associated with each other by non-covalent binding. At least 16 types of.alpha. chains and 8 types of.beta. chains have been found. A variety of molecular groups differing in ligand specificity are formed by the combination of these.alpha. and.beta. chains and 22 types of integrins have been known. Integrin has a function as cell membrane receptor protein for an adhesive molecule of an animal cell, expresses on a cell membrane and participates in the adhesion between a cell and an extracellular matrix (ECM) or between cells. When the cell adhesive molecule is combined with integrin, a signaling system in a cell starts moving and as a result, not only cell adhesion, but also cell evolution, cell proliferation, apoptosis, differentiation, cytoskeleton orientation, cell migration, histogenesis, cancer infiltration and metastasis, wound healing, blood coagulation and the like operate. It has been known that among these integrins, integrin.alpha.2.beta.1 of which the adhesive molecules are collagen and laminin participates in platelet aggregation, cancer infiltration and metastasis (HAYASHI Masao & MIYAMOTO Yasunori, PROTEIN, NUCLEIC ACID, ENZYME, Vol 44, pp130-135, (1999)) and angiogenesis (Donald R. Senger et al, Proc. Natl. Acad. Sci. USA, 94, 13612-13617, (1997)). It has come to be clarified that among these symptoms, the proliferation of cancer is closely related to angiogenesis. In recent years, it has been demonstrated experimentally that an antiangiogenesis agent can inhibit and further reduce proliferative cancer and no resistant cancer is generated in a transplant cancer model and there is shown a correlation between angiogenesis and exacerbations of many solid cancers such as mammary cancer, prostatic cancer, lung cancer and colonic cancer in clinical examinations (T. Boem et al, Nature, 390 (27) 404-407, (1997)). Also,.alpha.v.beta.1 of which the adhesive molecules are fibronectin and vitronectin participates in the adhesion of a cancer cell to a substrate and.alpha.v.beta.3 of which the adhesive molecules are vitronectin and thrombospongin and.alpha.v.beta.5 of which the adhesive molecule is vitronectin participate in angiogenesis, cancer metastasis and the regeneration of bone (Shattil, S. J., Thromb. Haemost., 74, 149-155, (1995), Friedlander M, et al, Sceience, 270, 1500-1502, (1995)). Further, it has been known that.alpha.3.beta.1 of which the adhesive molecules are fibronectin, collagen, laminin, laminin 5 and the like,.alpha.5.beta.1 of which the adhesive molecule is fibronectin and.alpha.6.beta.1 of
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which the adhesive molecules are laminin and laminin 5 participate in cancer infiltration and metastasis (MATSUURA Nariaki et al., JAPAN CLINIC, Vol 53, pp1643-1647, (1995), OTA Ichiro et al, CLINICAL PATHOLOGY, Vol 45, 528-533, (1997)). WO9950249 discloses the antagonist of integrin.alpha.v.beta.3, however there is no suggestion concerning the expression inhibitory action of integrin.alpha.v.beta.3. In JP-A 7-165708 and JP-A 8-231505, the same sulfonamide compound as that used in the present invention is disclosed; however, there is neither description nor hint concerning integrin expression inhibitory action. WO9301182 discloses-anti-tumor agents utilizing a specific tyrosine kinase inhibitive action of a compound having an indole skeleton. These agents are indolylmethylene-2-indolinone compounds, which differ from that of the present invention. WO964016 likewise discloses anti-tumor agents utilizing a specific tyrosine kinase inhibitory action of a compound having an indole skeleton. However, these agents are 2-indolinone-3-methylene derivatives, which differ from that of the present invention. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Method of treating angiogenesis-related disorders Inventor(s): Bingaman, David P.; (Fort Worth, TX), Gamache, Daniel A.; (Arlington, TX), Graff, Gustav; (Cleburne, TX), Kapin, Michael A.; (Arlington, TX), Yanni, John M.; (Burleson, TX) Correspondence: Alcon Research, LTD.; R&d Counsel, Q-148; 6201 South Freeway; Fort Worth; TX; 76134-2099; US Patent Application Number: 20030187072 Date filed: February 14, 2003 Abstract: The use of 3-benzolphenylacetic acids and derivatives, including nepafenac, to treat angiogenesis-related disorders, including ophthalmic angiogenesis-related disorders such as diabetic retinopathy and exudative macular degeneration, is disclosed. Excerpt(s): 3-benzolphenylacetic acid and certain of its derivatives are known to possess anti-inflammatory activity. U.S. Pat. Nos. 4,254,146, 4,045,576, 4,126,635, and 4,503,073, and U.K. Patent Application Nos. 2,071,086A and 2,093,027A disclose various 3benzolphenylacetic acids, salts and esters, and hydrates thereof, having antiinflammatory activity. U.S. Pat. No. 4,568,695 discloses 2-amino-3-benzoylphenylethyl alcohols having anti-inflammatory activity. U.S. Pat. No. 4,313,949 discloses 2-amino-3benzoyl-phenylacetamides having anti-inflammatory activity. This invention relates to the use of certain 3-benzolphenylacetic acids and derivatives to treat or prevent angiogenic diseases. Certain derivatives of 2-amino-3-benzoylbenzeneacetic acid (amfenac) and 2-amino-3-(4-chloro-benzoyl)benzeneacetic acid have also been evaluated by Walsh et al., J. Med Chem., 33:2296-2304 (1990), in an attempt to discover nonsteroidal anti-inflammatory prodrugs with minimal or no gastrointestinal side effects upon oral administration. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Method of treating diabetes Inventor(s): Jerling, Markus; (San Francisco, CA), Wolff, Andrew; (San Francisco, CA) Correspondence: Pauline Ann Clarke; CV Therapeutics, INC.; 3172 Porter Drive; Palo Alto; CA; 94304; US Patent Application Number: 20040063717 Date filed: May 21, 2003 Abstract: Methods are provided for treating diabetes, lowering plasma level of HbA1c, glucose plasma levels, total cholesterol plasma level, and/or triglyceride plasma level while increasing HDL cholesterol levels and delaying onset of diabetic retinopathy in a diabetic, pre-diabetic, or non-diabetic mammal while minimizing undesirable side effects. Excerpt(s): Priority is claimed to U.S. Provisional Application Serial No. 60/382,781, filed May 21, 2002, and to U.S. Provisional Application Serial No. 60/459,332, filed Mar. 31, 2003, the complete disclosures of which are hereby incorporated by reference. Methods are provided for treating diabetes, lowering plasma level of HbA1c, glucose plasma levels, total cholesterol plasma levels, and/or triglyceride plasma level while increasing HDL cholesterol levels and delaying onset of diabetic retinopathy in a diabetic, pre-diabetic, or non-diabetic mammal while minimizing undesirable side effects. Diabetes mellitus is a disease characterized by hyperglycemia; altered metabolism of lipids, carbohydrates and proteins; and an increased risk of complications from vascular disease. Diabetes is an increasing public health problem, as it is associated with both increasing age and obesity. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Methods and compositions of treating and/or preventing diabetic retinopathy with pericyte apoptosis inhibitors Inventor(s): Denis, Ulriche; (Caluire et Cuire, FR), Lagarde, Michel; (Decines, FR), Lecomte, Marc; (Lissieu, FR), Paget, Clarisse; (Lyon, FR), Wiernsperger, Nicolas; (Orlienas, FR) Correspondence: IP Department OF Piper Rudnick Llp; 3400 Two Logan Square; 18th And Arch Streets; Philadelphia; PA; 19103; US Patent Application Number: 20030216290 Date filed: April 23, 2003 Abstract: A method of preventing or treating diabetic retinopathy is disclosed including administering to a mammal a therapeutically effective amount of an inhibitor of retinal pericyte apoptosis. Also disclosed is a pharmaceutical composition which treats and/or prevents diabetic retinopathy comprising as an active agent a therapeutically effective amount of at least one inhibitor of retinal pericyte apoptosis and a pharmaceutically acceptable carrier. Excerpt(s): This is a continuation of PCT/FR01/03306 filed Oct. 26, 2001, which claims benefit from French Application No. 00/13640 filed Oct. 24, 2000. This invention relates to methods of treating and/or preventing diabetic retinopathy with pericyte apoptosis inhibitors. Diabetic retinopathy represents one of the most debilitating microvascular complications of diabetes. It can lead to blindness in its final stage (Grange, 1995; Frank, 1996; Aiello LP et al., 1998). It is the second leading cause of acquired blindness in
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developed countries, after macular degeneration of the aged (Nathan et al., 1991). The risk of a diabetic patient becoming blind is estimated to be 25 times greater than that of the general population (Kahn and Hiller, 1974). At present there is no preventive or curative pharmacological treatment for this complication. The only treatment is laser retinal photocoagulation or vitrectomy in the most severe cases (Frank, 1995; Aiello, 1998). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Multipurpose diode laser system for ophthalmic laser treatments Inventor(s): Berndt, Detlev; (Koln, DE), Maughan, Julian; (Salisbury, GB), Neuberger, Wolfgang; (F.T. Labuan, MY) Correspondence: Bolesh J. Skutnik Phd, JD; 515 Shaker Road; East Longmeadow; MA; 01028; US Patent Application Number: 20040116909 Date filed: December 11, 2002 Abstract: A laser device and method for treating ophthalmic diseases is enclosed. The device comprises a system for irradiating the eye with electromagnetic irradiation with a wavelength in the range of 654-681 nm. The system preferably comprises a laser source and ancillary equipment to direct and regulate the radiation. The use of this wavelength range makes the device effective for a wide variety of ophthalmic indications. It is capable of providing photocoagulation treatments for diseases such as glaucoma, diabetic retinopathy and age-related macular degeneration. The system is also useful for photodynamic therapy. Also disclosed are laser diodes with high beam quality and slit lamp adaptors to further enhance the versatility of the system. Excerpt(s): The invention relates to ophthalmic laser treatments, particularly to devices and systems capable of performing multiple ophthalmic photocoagulation treatments. U.S. Pat. No. 5,295,989 describes a light cable in an apparatus for ophthalmic treatment consisting of a plurality of optical fibers. A preferred embodiment utilizes an Argon laser beam as a treatment light source. Many of the current photocoagulators are of an inconveniently and inefficiently high cost, size and complexity. For example, conventional Krypton and Argon lasers are capable of emitting sufficient power levels for photocoagulation but are bulky, technically complex, and are inefficient "(below 0.1%) requiring up to 40 kW of three phase power and associated water cooling" to remove excess heat. (see U.S. Pat. No. 4,917,486) Thus, these setups are expensive and often require fixed installations. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Preventives and remedies for complications of diabetes Inventor(s): Kitahara, Masaki; (Minamisaitama-gun, JP), Mori, Sijiro; (Chiba-shi, JP), Saito, Yasushi; (Chiba-shi, JP), Takemoto, Minoru; (Akita-shi, JP), Tamaki, Taro; (Setagaya-ku, JP) Correspondence: Oliff & Berridge; P O Box 19928; Alexandria; VA; 22320; US Patent Application Number: 20040087597 Date filed: July 2, 2003
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Abstract: The present invention relates to the pharmaceutical useful for the prevention and the treatment of diabetic complications such as diabetic nephropathy, diabetic neuropathy, diabetic retinopathy and diabetic angiopathy among others, and to the prophylaxis and/or treatment drug for diabetic complications with the compound shown in the formula (1) 1(wherein R is organic group, X is --CH.sub.2CH.sub.2-- or -CH.dbd.CH--, and M is hydrogen atom, C.sub.1-10 alkyl group or physiologically acceptable cation group) or its lactonized form as the active ingredient. Excerpt(s): The present invention relates to the prophylactic and therapeutic agent with compound having inhibitory effect on 3-hydroxy-3-methylglutary- l-CoA (HMG CoA) reductase activity as the active ingredient for diabetic complications. The invention especially relates to the pharmaceutical to prevent and/or treat the onset and the progression of diabetic nephropathy, diabetic neuropathy, diabetic retinopathy and diabetic angiopathy. Diabetes mellitus is known to lead to the diabetic complications such as diabetic nephropathy, diabetic neuropathy, diabetic retinopathy or diabetic angiopathy, and the strict control of the blood glucose may be required for their prevention and treatment thereof. The fibrosis and the calcification of the tissues are often observed in these complications. Under the high blood glucose condition, glycosylated proteins which are the modulators for cell function are produced, and the accumulation of sorbitol due to the activation of intracellular polyol pathway is observed, leading to the activation of intracellular protein kinase C (PKC) which results in abnormality of glomerular cells in the kidney, nerve cells or arterial endothelial cells, and induces the accumulation of extracellular matrices and the calcification. The accelerated expression of extracellular matrices such as type IV collagen or fibronectin is well documented (Cagliero E. et al.: J. Clin. Invest., 82, 735-738 (1988), Haneda M. et al. : Diabetologia, 34, 198-200 (1991), Doi T. et al.: Proc. Natl. Acad. Sci. USA, 89, 28732877(1992)), but in recent days there are several papers reporting that the expression of osteopontin in the kidney and blood vessels markedly increases under diabetic condition and the expression of osteopontin thus accelerated may be in some ways related to diabetic nephropathy or diabetic angiopathy (Takemoto M. et al. : Arterioscler. Thromb. Vasc. Biol., 20, 624-628 (2000), Takemoto M. et al. : Ann. NY Acad. Sci., 902, 357-363 (2000)). From these findings, it is expected that the suppression of the expression of osteopontin as an extracellular matrices whose expression is accelerated in the kidney and arterial wall under the diabetic condition may be prophylactically effective on the onset or the aggravation of diabetic nephropathy or diabetic angiopathy. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Sigma receptor ligands and their medical uses Inventor(s): Dexter, Michael; (London, GB), Eccles, Suzanne Amy; (Sutton, GB), Spruce, Barbara Ann; (Dundee, GB) Correspondence: Dann, Dorfman, Herrell & Skillman; 1601 Market Street; Suite 2400; Philadelphia; PA; 19103-2307; US Patent Application Number: 20040019060 Date filed: June 5, 2003 Abstract: The present invention is based on the finding that sigma receptor ligands can modulate endothelial cell proliferation and/or survival, and hence control angiogenesis, and in particular that sigma receptor ligand antagonists can be used to inhibit angiogenesis aid so treat conditions such as psoriasis, diabetic retinopathy and cancer. Exemplary compounds include IPAG and rimcazole.
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Excerpt(s): The present invention relates to the use of sigma receptor ligands to modulate endothelial cell proliferation and/or survival, thereby controlling angiogenesis. In the normal adult body, most endothelial cells are quiescent, entering mitosis only in response to tissue injury or during menstruation and parturition. However, in pathological states including psoriasis and diabetic retinopathy, endothelial cells may proliferate leading to angiogenesis, the development of new blood vessels. It is also now well recognised that for any cancer to grow beyond a few millimetres in diameter, neoangiogensis is essential and that tumour cells secrete a variety of angiogenic cytokines which stimulate endothelial cell proliferation. One of the most important is vascular endothelial growth factor (VEGF) which also increases the permeability of newly formed vessels. Thus, in cancer, angiogenesis is critical for the development of solid cancers and also provides the conduit through which tumour cells may spread to other parts of the body. However, since a small area of capillary can provide nutrients for a relatively large volume of surrounding cancer cells, any inhibition of endothelial cell proliferation will "amplify" the effect on tumour cells, making this a promising approach for the treatment of cancer. Several different antiangiogenic agents have been shown to be potent inhibitors of tumour growth and spread. WO00/00599 discloses that opioid-like agents, including sigma receptor ligands, can be used to cause preferential cell cycle division arrest and apoptosis in populations of diseased cells as compared to normal cells, and in particular that apoptotic effects tend to be greater in tumour cells as compared to normal, non-diseased cells. These effects were demonstrated in this application in in vitro experiments using pure cultures of tumour cells. The results show that normal cells are insensitive to induction of cell cycle division arrest and apoptosis at doses of sigma receptor ligands that are lethal or cytostatic to tumour cells. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Treatment of ocular disease Inventor(s): Peyman, Gholam A.; (New Orleans, LA) Correspondence: Wood, Herron & Evans, Llp; 2700 Carew Tower; 441 Vine Street; Cincinnati; OH; 45202; US Patent Application Number: 20040092435 Date filed: November 7, 2002 Abstract: A method and article to treat ocular disease with Cyclosporin A alone or with compounds related to Cyclosporin A for intraocular injection or implantation. Treatment does not result in ocular toxicity and encompasses age related macular degeneration, retinitis pigmentosa, and retinopathy such as diabetic retinopathy. Excerpt(s): The invention is directed to therapeutic treatment of age-related macular degeneration, retinitis pigmentosa, and diabetic retinopathy with Cyclosporin A. The immunomodulator Cyclosporin A (cyclosporine, topical formulation Arrestase.RTM., Allergan Inc.) has been used to treat glaucoma, corticosteroid-induced ocular hypertension, allograft rejection, infections, and ocular surface disease. Its use has been reported for the treatment of uveitis (inflammation of the uvea) by topical, intravitreal or systemic administration with doses of 0.05%, 0.1%, and 0.5%. Cyclosporin A has good penetration into the cornea but not into the anterior chamber, and does not increase intraocular pressure or cause cataracts. Its known toxicity had previously limited its use for other ocular diseases. A method of treating age-related macular degeneration, retinitis pigmentosa, and diabetic retinopathy in the absence of substantial toxicity by
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administering Cyclosporin A in an effective amount and in a pharmaceutically acceptable formulation. "Treating" includes preventing progression of pre-existing disease, delaying onset and/or severity of disease, and ameliorating or reducing the severity, frequency, duration, etc., of one or more symptoms of disease. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Vascular endothelial growth factor-2 Inventor(s): Coleman, Timothy; (Gaithersburg, MD) Correspondence: Human Genome Sciences Inc; 9410 Key West Avenue; Rockville; MD; 20850 Patent Application Number: 20030215921 Date filed: August 3, 2001 Abstract: Disclosed are human VEGF-2 polypeptides, biologically active, diagnostically or therapeutically useful fragments, analogs, or derivatives thereof, and DNA(RNA) encoding such VEGF-2 polypeptides. Also provided are procedures for producing such polypeptides by recombinant techniques and antibodies and antagonists against such polypeptides. Such polypeptides and polynucleotides may be used therapeutically for stimulating wound healing and for vascular tissue repair. Also provided are methods of using the antibodies and antagonists to inhibit tumor angiogenesis and thus tumor growth, inflammation, diabetic retinopathy, rheumatoid arthritis, and psoriasis. Excerpt(s): This application claims benefit of 35 U.S.C. section 119(e) based on copending U.S. Provisional Application Serial No. 60/223,276, filed Aug. 4, 2000, herein incorporated by reference in its entirety. The present invention relates to newly identified polynucleotides, polypeptides encoded by such polynucleotides, the use of such polynucleotides and polypeptides, as well as the production of such polynucleotides and polypeptides. The polypeptides of the present invention have been identified as members of the vascular endothelial growth factor family. More particularly, the polypeptides of the present invention are human vascular endothelial growth factor 2 (VEGF-2). The invention also relates to inhibiting the action of such polypeptides. The formation of new blood vessels, or angiogenesis, is essential for embryonic development, subsequent growth, and tissue repair. Angiogenesis is also an essential part of certain pathological conditions, such as neoplasia (i.e., tumors and gliomas). Abnormal angiogenesis is associated with other diseases such as inflammation, rheumatoid arthritis, psoriasis, and diabetic retinopathy (Folkman, J. and Klagsbrun, M., Science 235:442-447(1987)). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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VEGF activity inhibitor Inventor(s): Sato, Yasufumi; (Sendai-shi, JP), Shitara, Kenya; (Fujisawa-shi, JP) Correspondence: Nixon & Vanderhye, PC; 1100 N Glebe Road; 8th Floor; Arlington; VA; 22201-4714; US Patent Application Number: 20030175271 Date filed: April 30, 2003
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Abstract: The present invention provides a therapeutic agent which is effective for solid tumors, arthritis in chronic rheumatoid arthritis, diabetic retinopathy, retinopathy of prematurity, psoriasis, or the like, comprising a combination of a substance which inhibits signal transduction mediated by human VEGF receptor Flt-1 which is useful for the diagnosis or treatment of diseases in which their morbid states progress by abnormal angiogenesis, such as proliferation or metastasis of solid tumors, arthritis in chronic rheumatoid arthritis, diabetic retinopathy, retinopathy of prematurity, psoriasis, and the like with a substance which inhibits signal transduction mediated by human VEGF receptor KDR. Excerpt(s): The present invention relates to a medicament comprising a combination of a substance which inhibits signal transduction mediated by human VEGF receptor Flt-1 with a substance which inhibits signal transduction mediated by human VEGF receptor KDR and is useful for treatment of diseases in which their morbid states progress by abnormal angiogenesis, such as proliferation or metastasis of solid tumors, arthritis in rheumatoid arthritis, diabetic retinopathy, retinopathy of prematurity, psoriasis, and the like. Angiogenesis plays an important role in formation of a circulatory system and construction of various tissues at fetus in vertebrates, is directly involved in the formation of the corpus luteum during the sexual cycle, transient proliferation of the uterine endometrium and formation of the placenta in mature individuals (females). With regard to pathological states, angiogenesis is involved in the proliferation or metastasis of solid tumors and formation or acceleration of morbidity in diabetic retinopathy and rheumatoid arthritis [J. Biol. Chem., 267: 10931 (1992)]. Angiogenesis occurs by the secretion of an angiogenesis factor and involves the process of a tube formation and producing a new blood vessel. During this process, the basement membrane and interstitum are destroyed by a protease secreted from endothelial cells of an existing blood vessel around the secreted angiogenesis factor, followed by subsequent migration and proliferation of vascular endothelial cells [J. Biol. Chem., 267: 10931 (1992)]. Factors which induce angiogenesis include vascular permeability factor (hereinafter referred to as "VPF") and vascular endothelial growth factor (hereinafter referred to as "VEGF") (hereinafter referred to as "VPF/VEGF"). These factors are considered the most important factors in pathological and non-pathological angiogenesis [Advances in Cancer Research, 67: 281 (1995)]. VPF/VEGF is a protein having a molecular weight of about 40,000 constituted by homodimers, which had been reported to be independent molecules as vascular permeability factor (VPF) in 1983 [Science, 219: 983 (1983)] and as vascular endothelial growth factor (VEGF) in 1989 [Biochem. Biophys. Res. Comm., 161: 851 (1989)], but it has been revealed as the results of cDNA cloning that they are the same substance [Science, 246: 1306 (1989); Science, 246: 1309 (1989)] (hereinafter, the term "VPF/VEGF" is referred to as "VEGF"). Beyond the activity of VEGF upon vascular endothelial cells described above, VEGF has also been shown to have a growth enhancing activity [Biochem. Biophys. Res. Comm., 161: 851 (1989)], a migration enhancing activity [J. Immunology, 152: 4149 (1994)], a metalloprotease secretion enhancing activity [J. Cell Physiol., 153: 557 (1992)], a urokinase and tPA secretion enhancing activity [Biochem. Biophys. Res. Comm., 181: 902 (1991)], and the like. Furthermore, VEGF has been shown to have an angiogenesis enhancing activity [Circulation, 92 suppl II: 365 (1995)], a vascular permeability enhancing activity [Science, 219: 983 (1983)], and the like as its in vivo activities. It has been reported that VEGF is a growth factor having extremely high specificity for vascular endothelial cells [Biochem. Biophys. Res. Comm., 161: 851 (1989)] and that four proteins having different molecular weight are present due to alternative splicing of mRNA [J. Biol. Chem., 267: 26031 (1991)]. Among diseases accompanied by angiogenesis, it has been reported that VEGF plays an important role in the proliferation
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or metastasis of solid tumors and formation of morbid states of diabetic retinopathy and rheumatoid arthritis. With regard to solid tumors, production of VEGF in a number of human tumor tissues has been reported, such as in renal carcinoma [Cancer Research, 54: 4233 (1994)], breast cancer [Human Pathology, 26: 86 (1995)], brain tumor [J. Clinical Investigation, 91: 153 (1993)], gastrointestinal cancer [Cancer Research, 53: 4727 (1993)], ovarian cancer [Cancer Research, 54: 276 (1994)], and the like. Also, results of a study on the correlation between VEGF expression quantity in tumors and survival ratio of patients in patients with breast cancer have revealed that tumor angiogenesis is more active in tumors expressing high levels of VEGF than low VEGF expression tumors and that the survival ratio is lower in breast cancer patients having high VEGF expression tumors than breast cancer patients having low VEGF expression tumors [Japanese J. Cancer Research, 85: 1045 (1994)]. It has been reported also that an anti-VEGF monoclonal antibody inhibited tumor growth in a xenograft model test system in which a human tumor was transferred into nude mice by subcutaneous transplantation [Nature, 362: 841 (1993)]. Also, it has been reported that, in a metastatic cancer model of a human tumor in nude mice, an anti-VEGF monoclonal antibody inhibited metastasis of the tumor [Cancer Research, 56: 921 (1996)]. Additionally, since a high concentration of VEGF was detected in human carcinomatous pleural perfusions and ascites, the possibility that VEGF is a major factor involved in the retention of pleural perfusions and ascites has been suggested [Biochimica et Biophysica Acta, 1221: 211 (1994)], and inhibition of the retention of pleural perfusions and ascites is expected by blocking VEGF. 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 diabetic retinopathy, 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 “diabetic retinopathy” (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 diabetic retinopathy. You can also use this procedure to view pending patent applications concerning diabetic retinopathy. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.
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CHAPTER 6. BOOKS ON DIABETIC RETINOPATHY Overview This chapter provides bibliographic book references relating to diabetic retinopathy. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on diabetic retinopathy 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 “diabetic retinopathy” (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 diabetic retinopathy: •
Diabetic Retinopathy: Practical Management Source: Philadelphia, PA: Lippincott-Raven Publishers. 1993. 191 p. Contact: Available from Lippincott-Raven Publishers. 1185 Avenue of the Americas, New York, NY 10036. (212) 930-9500. Fax (212) 869-3495. PRICE: $95 (as of 1995). ISBN: 0397511671. Summary: In this medical textbook, the authors summarize the essentials in evaluating and treating patients with diabetic retinopathy. Ten chapters cover the epidemiology of diabetic retinopathy; the classifications of diabetic retinopathy, including the most recent ETDRS classification of nonproliferative retinopathy; the results of the national collaborative studies involved with the management and treatment of diabetic retinopathy and its complications; the management of nonproliferative diabetic retinopathy; the management of diabetic macular edema, particularly the use of
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modified grid laser photocoagulation; the management of proliferative diabetic retinopathy; the indications for vitreous surgery; the indications for fluorescein angiography in the management of diabetic retinopathy; the complications and side effects of treatment; and special cases in the management of patients with various problems associated with diabetic retinopathy, including cataracts, macular edema, and pregnancy. Each chapter includes numerous black-and-white reproductions and references; a subject index concludes the volume. •
For My Patient: Diabetic Retinopathy Source: San Francisco, CA: Retina Research Fund, St. Mary's Hospital and Medical Center. 1992. 69 p. Contact: Available from Retina Research Fund, St. Mary's Hospital and Medical Center. P.O. Box 640350, San Francisco, CA 94164-0350. (415) 668-1000. PRICE: $3.50. Summary: This large-print, illustrated booklet (full-color photographs and drawings) for patients with diabetic retinopathy (DR) and their families discusses the characteristics and treatment of this disease, how it affects eyesight, what factors can affect the disease, and what can be done about it. Topics include: how the eye works; the retina; the two types of DR; laser treatment; fluorescein angiography; early diagnosis of background diabetic retinopathy (BDR); laser treatment for BDR; proliferative diabetic retinopathy (PDR); laser treatment for PDR: vitreous hemorrhage; retinal detachment; closure of macular vessels; preventing DR; emotional factors in diabetes. Detailed answers to a number of commonly asked questions concerning laser treatment and vitrectomy surgery for PDR are included.
Chapters on Diabetic Retinopathy In order to find chapters that specifically relate to diabetic retinopathy, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and diabetic retinopathy 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 “diabetic retinopathy” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on diabetic retinopathy: •
Eye: Diabetic Retinopathy and Ophthalmopathy Source: in Sperling, M.A. Type 1 Diabetes: Etiology and Treatment. Totowa, NJ: Humana Press Inc. 2003. p. 393-407. 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: This chapter on complications of type 1 diabetes that affect the eye is from a book in which well-recognized physicians and researchers review the latest thinking about the causes of type 1 diabetes and the best approaches to treating both its acute and chronic complications. Topics include epidemiology, diabetic eye disease, diabetic retinopathy, and other clinically relevant ocular complications of type 1 diabetes. The authors conclude that there are no cures for the ocular complications of diabetes
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mellitus, but if careful and regular follow up can be maintained by retinal specialists, most patients' retinopathy can be adequately managed with laser treatment. The key to successful treatment is based on the ability to grade retinopathy for which there are explicit guidelines for treatment and follow up. When laser photocoagulation fails, vitreoretinal microsurgery offers the patients with diabetes an opportunity of restoring vision in situations that previously would have inevitably led to blindness. 6 color figures. 1 table. 60 references.
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CHAPTER 7. MULTIMEDIA ON DIABETIC RETINOPATHY Overview In this chapter, we show you how to keep current on multimedia sources of information on diabetic retinopathy. 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 diabetic retinopathy is the Combined Health Information Database. You will need to limit your search to “Videorecording” and “diabetic retinopathy” 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 “diabetic retinopathy” (or synonyms) into the “For these words:” box. The following is a typical result when searching for video recordings on diabetic retinopathy: •
Evaluation and Treatment of Diabetic Retinopathy Source: San Francisco, CA: American Academy of Ophthalmology. 1990. Contact: Available from American Academy of Ophthalmology. P.O. Box 7424. San Francisco, CA 94120. (415) 561-8540. PRICE: $65 (members) or $85 (non-members). Order Number 0250903. Summary: This videocassette aids the opthalmologist in identifying diabetic retinopathy and providing timely treatment. The authors describe methods to minimize the side effects of managing this disease, and discuss its impact on the patient's vision and quality of life. Production of this tape was supported from educational grants from two pharmaceutical companies. (AA).
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Management of Diabetic Retinopathy for the Primary Care Physician Source: San Francisco, CA: American Academy of Ophthalmology. 1990.
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Contact: Available from American Academy of Ophthalmology. P.O. Box 7424. San Francisco, CA 94120. (415) 561-8540. PRICE: $65 (members) or $85 (non-members). Order Number 0250893. Summary: This videocassette helps the primary care physician identify and distinguish between the various stages of diabetic retinopathy. The author covers the associated risks of each stage, the essentials of followup and treatment, a brief description of the pathophysiology, and the importance of timely referral. Production of this tape was supported from educational grants from two pharmaceutical companies. (AA).
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CHAPTER 8. PERIODICALS AND NEWS ON DIABETIC RETINOPATHY Overview In this chapter, we suggest a number of news sources and present various periodicals that cover diabetic retinopathy.
News Services and Press Releases One of the simplest ways of tracking press releases on diabetic retinopathy 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 “diabetic retinopathy” (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 diabetic retinopathy. 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 “diabetic retinopathy” (or synonyms). The following was recently listed in this archive for diabetic retinopathy: •
Pyridoxamine protects against diabetic retinopathy in an animal model Source: Reuters Industry Breifing Date: September 25, 2002
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Fidarestat checks diabetic retinopathy in diabetic rats Source: Reuters Industry Breifing Date: December 19, 2003
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Color vision test detects diabetic retinopathy before morphological changes Source: Reuters Medical News Date: June 03, 2003
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Aldose reductase polymorphism linked to diabetic retinopathy in Asian Indians Source: Reuters Medical News Date: April 22, 2003
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Thiamine derivative prevents diabetic retinopathy in animal model Source: Reuters Medical News Date: February 17, 2003
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New Clues To Molecular Mechanisms Of Diabetic Retinopathy Identified Source: Reuters Medical News Date: April 07, 1998
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Complication-Free Duration Not Linked To Diabetic Retinopathy Risk Source: Reuters Medical News Date: March 31, 1998
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Screening For Diabetic Retinopathy Is Highly Cost Effective Source: Reuters Medical News Date: September 04, 1996 The NIH
Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine. Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name. Market Wire Market Wire is more focused on technology than the other wires. To browse the latest press releases by topic, such as alternative medicine, biotechnology, fitness, healthcare, legal, nutrition, and pharmaceuticals, access Market Wire’s Medical/Health channel at http://www.marketwire.com/mw/release_index?channel=MedicalHealth. Or simply go to Market Wire’s home page at http://www.marketwire.com/mw/home, type “diabetic retinopathy” (or synonyms) into the search box, and click on “Search News.” As this service
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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 “diabetic retinopathy” (or synonyms). If you know the name of a company that is relevant to diabetic retinopathy, 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 “diabetic retinopathy” (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 “diabetic retinopathy” (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 diabetic retinopathy: •
Nephropathy in NIDDM as Compared With IDDM Source: Diabetes News. 16(2): 5-8. 1995. Contact: Available from Excerpta Medica. P.O. Box 1126, 1000 BC Amsterdam, Netherlands. Summary: In this article, the author reports on nephropathy in people with noninsulindependent diabetes mellitus (NIDDM) and insulin-dependent diabetes mellitus (IDDM). The author notes that renal disease in both NIDDM and IDDM is frequently associated with poor metabolic control as well as with elevated blood pressure. To date, these two risk factors appear to be the only ones that are clearly linked to the development of renal disease, though several other modifying factors are known. Topics covered include population-based studies of individuals without known diabetes; renal function at the clinical diagnosis of diabetes; normal albumin excretion and the transition to microalbuminuria; overt diabetic retinopathy; end-stage renal failure; epidemiological studies; and screening. 2 figures. 2 tables. 12 references. (AA-M).
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American College of Physicians Home Medical Guide to Diabetes Source: New York, NY: Dorling Kindersley Publishing, Inc. 2000. 96 p. Contact: Available from Dorling Kindersley Publishing, Inc. 95 Madison Avenue, New York, NY 10016. (212) 213-4800. Fax (212) 213-5240. E-mail:
[email protected]. Website: www.dk.com. PRICE: $6.95 plus shipping and handling. ISBN: 0789452006. Summary: This illustrated guide provides people who have diabetes with expert advice on understanding and living with this chronic disease. The guide begins with a section that explains what diabetes is and what causes it. Known causes include heredity, infection, and environmental factors. The next section focuses on tests used to diagnosis diabetes, including the oral glucose tolerance test and urine tests. This is followed by sections that discuss the treatment of diabetes with diet and medications such as sulfonylureas, benzoic acid derivatives, biguanides, acarbose, thiazolidinediones, and insulin. The next section is devoted to monitoring blood glucose levels through blood and urine tests. Hypoglycemia is the focus of the next section. Topics include preventing and treating this acute complication. This is followed by a section that discusses exercising, socializing, traveling, coping with illness, and having a baby. The next section deals with issues related to children who have diabetes, including home monitoring, hypoglycemia, food difficulties, family reactions, and behavioral issues. The topic of the next section is complications of diabetes, including diabetic retinopathy, diabetic nephropathy, diabetic neuropathy, erectile dysfunction, skin problems, cardiovascular problems, and foot problems. This is followed by a section that explains the medical procedures and information that a person who has diabetes should expect from his or her health care professional. The final section addresses the issues of preventing, curing, and treating diabetes in the future. In addition, the guide presents answers to some common questions about diabetes and provides information on useful resources and online sites. 12 figures.
Academic Periodicals covering Diabetic Retinopathy Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to diabetic retinopathy. In addition to these sources, you can search for articles covering diabetic retinopathy 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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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 Institute10: •
Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm
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National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/
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National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html
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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/
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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.11 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:12 •
Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html
•
HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html
•
NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html
•
Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/
•
Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html
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Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html
•
Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/
•
Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html
•
Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html
•
Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html
•
MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html
11
Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 12 See http://www.nlm.nih.gov/databases/databases.html.
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•
Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html
•
Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html
The NLM Gateway13 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.14 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “diabetic retinopathy” (or synonyms) into the search box and click “Search.” The results will be presented in a tabular form, indicating the number of references in each database category. Results Summary Category Journal Articles Books / Periodicals / Audio Visual Consumer Health Meeting Abstracts Other Collections Total
Items Found 13552 176 897 16 37 14678
HSTAT15 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.16 These documents include clinical practice guidelines, quickreference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.17 Simply search by “diabetic retinopathy” (or synonyms) at the following Web site: http://text.nlm.nih.gov.
13
Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.
14
The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH). 15 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 16 17
The HSTAT URL is http://hstat.nlm.nih.gov/.
Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations.
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Coffee Break: Tutorials for Biologists18 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.19 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.20 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.
Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are some examples that may interest you: •
CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.
•
Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.
18 Adapted 19
from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html.
The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 20 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process.
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APPENDIX B. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. Since new guidelines on diabetic retinopathy can appear at any moment and be published by a number of sources, the best approach to finding guidelines is to systematically scan the Internetbased services that post them.
Patient Guideline Sources The remainder of this chapter directs you to sources which either publish or can help you find additional guidelines on topics related to diabetic retinopathy. 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 diabetic retinopathy. 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 “diabetic retinopathy”:
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Diabetes http://www.nlm.nih.gov/medlineplus/diabetes.html Diabetic Diet http://www.nlm.nih.gov/medlineplus/diabeticdiet.html Diabetic Eye Problems http://www.nlm.nih.gov/medlineplus/diabeticeyeproblems.html Diabetic Kidney Problems http://www.nlm.nih.gov/medlineplus/diabetickidneyproblems.html Diabetic Nerve Problems http://www.nlm.nih.gov/medlineplus/diabeticnerveproblems.html Eye Diseases http://www.nlm.nih.gov/medlineplus/eyediseases.html Juvenile Diabetes http://www.nlm.nih.gov/medlineplus/juvenilediabetes.html You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The Combined Health Information Database (CHID) CHID Online is a reference tool that maintains a database directory of thousands of journal articles and patient education guidelines on diabetic retinopathy. 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: •
Understanding Diabetic Retinopathy Source: Yardley, PA: The StayWell Company: KRAMES Health and Safety Education. 2002. 16 p. Contact: StayWell Company: KRAMES Health and Safety Education. 780 Township Line Road, Yardley, PA 19067. (800) 333-3032. Fax: (866) 722-4377. E-mail:
[email protected]. Website: www.staywell.com. PRICE: Single copy free; $1.95 each. Item number: 11319. Summary: Diabetes damages blood vessels in the back of the eye. This condition is called diabetic retinopathy and can lead to vision loss or blindness. This booklet helps readers with diabetes understand diabetic retinopathy and how to prevent it or reduce its impact. Topics include eye anatomy, diabetes and the eye, how vision can change, managing one's health (including good blood glucose control), using the Amsler Grid (which helps readers track any changes in their vision), eye evaluation and monitoring (including the role of regular eye exams and what to expect during an eye exam), having
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laser treatments, having vitrectomy, and the importance of working in tandem with one's health care team. The brochure is illustrated with full-color drawings of patients and health care providers as well as anatomical drawings of the eye. The brochure concludes with the contact information for four resource organizations that can provide assistance. 31 figures. •
Diabetic Retinopathy: Information for Patients Source: Bethesda, MD: National Eye Institute, National Institutes of Health. 1995. 19 p. Contact: Available from National Eye Health Education Program. 2020 Vision Place, Bethesda, MD 20892-3655. (800) 869-2020 or (301) 496-5248. E-mail:
[email protected]. Single copy free; bulk copies available. Summary: This brochure helps people with diabetic retinopathy and their families better understand the disease. The brochure describes the cause, symptoms, diagnosis, and treatment of diabetic retinopathy. Topics include the physiology of the retina and how diabetic retinopathy damages the retina; risk factors for this disease; diagnostic testing, including the visual acuity test, pupil dilation, ophthalmoscopy, tonometry, and fluorescein angiography; treatment options, including laser surgery and vitrectomy; current research projects in this area; and recommendations for protecting one's vision. The brochure concludes with a list of resource organizations through which readers may get more information. The back pocket of the brochure includes a flyer providing suggestions for patients about talking and working with their health care providers.
•
Ophthalmoscopic Manifestations of Diabetic Retinopathy Source: Princeton, NJ: Novo Nordisk Pharmaceuticals Inc. September 1991. 7 p. Contact: Available from Novo Nordisk Pharmaceuticals Inc. 100 Overlook Center, Suite 200, Princeton, NJ 08540-7810. (800) 727-6500. PRICE: Single copy free. Order number 000-33R. Summary: This brochure presents photographs depicting progressive stages of diabetic retinopathy. A brief outline of the classification system used for nonproliferative and for proliferative diabetic retinopathy is included. The brochure stresses that physicians alert to the opthalmic manifestations of diabetic retinopathy can identify retinal abnormalities at an early stage when prevention of more serious diabetic eye disease is possible. The brochure concludes with a brief glossary.
•
Diabetic Retinopathy Source: San Bruno, CA: Krames Communications. 1997. 4 p. Contact: Available from Krames Communications. Order Department, 1100 Grundy Lane, San Bruno, CA 94066. (800) 333-3032. Fax (415) 244-4512. PRICE: $17.95 for package of 50 brochures. Summary: This brochure provides information about diabetic retinopathy. The brochure points out that controlling diabetes and other risk factors may prevent or limit retinopathy. People should watch their diets, get regular exercise, take medicines as prescribed, and check blood glucose levels as often as their health care professionals suggest. Topics include the causes and symptoms of diabetic retinopathy, regular eye exams, controlling diabetes and other risk factors, monitoring vision, and types of treatment. Because people can have diabetic retinopathy without knowing it, regular
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eye exams are especially important. The brochure includes colorful illustrations of people, a healthy eye, and an eye with retinopathy. (AA-M). •
Treating Diabetic Retinopathy: Setting Your Sights on Saving Your Vision Source: San Bruno, CA: StayWell Company. 2000. 15 p. Contact: Available from StayWell Company. Order Department, 1100 Grundy Lane, San Bruno, CA 94066-9821. (800) 333-3032. Fax (650) 244-4512. E-mail:
[email protected]. Website: www.staywell.com. PRICE: $1.75 plus shipping and handling; bulk copies available. Summary: This illustrated booklet provides people who have diabetes with information on preventing and treating diabetic retinopathy. This complication of diabetes may start without symptoms and worsen over time. In people who have retinopathy, the blood vessels in the eye may go through a series of changes, including the leakage or closure of capillaries or the growth of weak new capillaries. Types of diabetic retinopathy include nonproliferative and proliferative diabetic retinopathy. People who have nonproliferative retinopathy may have capillary leakage, capillary closure, or both. In proliferative retinopathy, new, but weak, blood vessels grow and burst. Regular eye examinations are important to monitor and catch any eye problems before vision damage occurs. During an eye evaluation, the doctor will obtain a medical history, measure vision with an eye chart or other special tools, and perform other diagnostic tests. Managing diabetes by controlling blood glucose levels and blood pressure, eating healthy meals, and exercising may slow the progress of diabetic retinopathy. If diabetic retinopathy does develop, one treatment option is laser surgery to reduce swelling, destroy closed blood vessels, seal weak vessels, and reduce or stop the growth of new blood vessels. In addition, removal of the vitreous may be needed if bleeding into the vitreous has occurred.
•
Diabetic Retinopathy: Healthy Eyes Mean a Better Life Source: St. Louis, MO: American Optometric Association. 1991. 2 p. Contact: Available from American Optometric Association. Order Department, 243 North Lindbergh Boulevard, St. Louis, MO 63141. (314) 991-4100. PRICE: Single copy free (bulk prices available). Order Number FS6. Summary: This patient education fact sheet provides information about diabetic retinopathy. As this disease can cause blindness, early diagnosis and treatment is essential. The fact sheet describes the beginning stages of diabetic retinopathy, how the disease progresses, and the types of treatment used to reduce the progression of this eye disease and decrease the risk of vision loss. The fact sheet concludes with a list of recommended steps to take to help prevent diabetic retinopathy. 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 diabetic retinopathy. 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
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rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •
AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats
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Family Village: http://www.familyvillage.wisc.edu/specific.htm
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Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/
•
Med Help International: http://www.medhelp.org/HealthTopics/A.html
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Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/
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Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/
•
WebMDHealth: http://my.webmd.com/health_topics
Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to diabetic retinopathy. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with diabetic retinopathy. 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 diabetic retinopathy. 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 “diabetic retinopathy” (or a synonym), and you will receive information on all relevant organizations listed in the database.
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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 “diabetic retinopathy”. 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 “diabetic retinopathy” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months. The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “diabetic retinopathy” (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.21
Finding a Local Medical Library The quickest method to locate medical libraries is to use the Internet-based directory published by the National Network of Libraries of Medicine (NN/LM). This network includes 4626 members and affiliates that provide many services to librarians, health professionals, and the public. To find a library in your area, simply visit http://nnlm.gov/members/adv.html or call 1-800-338-7657.
Medical Libraries in the U.S. and Canada In addition to the NN/LM, the National Library of Medicine (NLM) lists a number of libraries with reference facilities that are open to the public. The following is the NLM’s list and includes hyperlinks to each library’s Web site. These Web pages can provide information on hours of operation and other restrictions. The list below is a small sample of
21
Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.
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libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)22: •
Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/
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Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)
•
Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm
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California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html
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California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html
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California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html
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California: Gateway Health Library (Sutter Gould Medical Foundation)
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California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/
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California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp
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California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html
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California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/
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California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/
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California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/
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California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html
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California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/
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Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/
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Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/
•
Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/
22
Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.
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•
Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml
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Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm
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Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html
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Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm
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Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp
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Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/
•
Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm
•
Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html
•
Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/
•
Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm
•
Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/
•
Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/
•
Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/
•
Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm
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Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html
•
Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm
•
Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/
•
Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/
•
Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10
•
Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/
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•
Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html
•
Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp
•
Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp
•
Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/
•
Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html
•
Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm
•
Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp
•
Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/
•
Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html
•
Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/
•
Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm
•
Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/
•
Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html
•
Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm
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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)
•
National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html
•
National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/
•
National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/
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•
Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm
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New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/
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New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm
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New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm
•
New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/
•
New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html
•
New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/
•
New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html
•
New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/
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Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm
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Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp
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Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/
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Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/
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Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml
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Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html
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Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html
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Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml
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Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp
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Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm
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Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/
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South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp
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Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/
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Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/
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Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72
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ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •
ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html
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MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp
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Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/
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Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html
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On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/
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Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp
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Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm
Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a). The NIH suggests the following Web sites in the ADAM Medical Encyclopedia when searching for information on diabetic retinopathy: •
Basic Guidelines for Diabetic Retinopathy Diabetic retinopathy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001212.htm
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Signs & Symptoms for Diabetic Retinopathy Blindness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003040.htm Decreased visual acuity Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003029.htm High blood pressure Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003082.htm Loss of vision Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003040.htm
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Diagnostics and Tests for Diabetic Retinopathy Dilated Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003434.htm Retinal photography Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003846.htm
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Surgery and Procedures for Diabetic Retinopathy Laser surgery Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002958.htm
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Background Topics for Diabetic Retinopathy Incidence Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002387.htm Retina Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002291.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
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MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html
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Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/
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Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine
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DIABETIC RETINOPATHY DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 3-dimensional: 3-D. A graphic display of depth, width, and height. Three-dimensional radiation therapy uses computers to create a 3-dimensional picture of the tumor. This allows doctors to give the highest possible dose of radiation to the tumor, while sparing the normal tissue as much as possible. [NIH] Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] Ablate: In surgery, is to remove. [NIH] Ablation: The removal of an organ by surgery. [NIH] Acatalasia: A rare autosomal recessive disorder resulting from the absence of catalase activity. Though usually asymptomatic, a syndrome of oral ulcerations and gangrene may be present. [NIH] Accommodation: Adjustment, especially that of the eye for various distances. [EU] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Acidosis: A pathologic condition resulting from accumulation of acid or depletion of the alkaline reserve (bicarbonate content) in the blood and body tissues, and characterized by an increase in hydrogen ion concentration. [EU] Actin: Essential component of the cell skeleton. [NIH] Activities of Daily Living: The performance of the basic activities of self care, such as dressing, ambulation, eating, etc., in rehabilitation. [NIH] Acuity: Clarity or clearness, especially of the vision. [EU] Acyl: Chemical signal used by bacteria to communicate. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adaptation: 1. The adjustment of an organism to its environment, or the process by which it enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the intensity of light; the adjustment to such variations. 3. The decline in the frequency of firing of a neuron, particularly of a receptor, under conditions of constant stimulation. 4. In dentistry, (a) the proper fitting of a denture, (b) the degree of proximity and interlocking of restorative material to a tooth preparation, (c) the exact adjustment of bands to teeth. 5. In microbiology, the adjustment of bacterial physiology to a new environment. [EU] 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]
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Adipocytes: Fat-storing cells found mostly in the abdominal cavity and subcutaneous tissue. Fat is usually stored in the form of tryglycerides. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adolescence: The period of life beginning with the appearance of secondary sex characteristics and terminating with the cessation of somatic growth. The years usually referred to as adolescence lie between 13 and 18 years of age. [NIH] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH] 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] Adverse Effect: An unwanted side effect of treatment. [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 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] Aggravation: An increasing in seriousness or severity; an act or circumstance that intensifies, or makes worse. [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] 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] Aldose Reductase Inhibitor: A class of drugs being studied as a way to prevent eye and
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nerve damage in people with diabetes. Aldose reductase is an enzyme that is normally present in the eye and in many other parts of the body. It helps change glucose (sugar) into a sugar alcohol called sorbitol. Too much sorbitol trapped in eye and nerve cells can damage these cells, leading to retinopathy and neuropathy. Drugs that prevent or slow (inhibit) the action of aldose reductase are being studied as a way to prevent or delay these complications of diabetes. [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] Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Allograft: An organ or tissue transplant between two humans. [NIH] Alpha Particles: Positively charged particles composed of two protons and two neutrons, i.e., helium nuclei, emitted during disintegration of very heavy isotopes; a beam of alpha particles or an alpha ray has very strong ionizing power, but weak penetrability. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Alternative Splicing: A process whereby multiple protein isoforms are generated from a single gene. Alternative splicing involves the splicing together of nonconsecutive exons during the processing of some, but not all, transcripts of the gene. Thus a particular exon may be connected to any one of several alternative exons to form messenger RNA. The alternative forms produce proteins in which one part is common while the other part is different. [NIH] Amaurosis: Partial or total blindness from any cause. [NIH] Amaurosis Fugax: Partial amaurosis, which is sudden and transitory, and associated with headache, vertigo, and nausea. [NIH] Amblyopia: A nonspecific term referring to impaired vision. Major subcategories include stimulus deprivation-induced amblyopia and toxic amblyopia. Stimulus deprivationinduced amblopia is a developmental disorder of the visual cortex. A discrepancy between visual information received by the visual cortex from each eye results in abnormal cortical development. Strabismus and refractive errors may cause this condition. Toxic amblyopia is a disorder of the optic nerve which is associated with alcoholism, tobacco smoking, and other toxins and as an adverse effect of the use of some medications. [NIH] Ameliorating: A changeable condition which prevents the consequence of a failure or accident from becoming as bad as it otherwise would. [NIH] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (-
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COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Anaphylatoxins: The family of peptides C3a, C4a, C5a, and C5a des-arginine produced in the serum during complement activation. They produce smooth muscle contraction, mast cell histamine release, affect platelet aggregation, and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from strongest to weakest is C5a, C3a, C4a, and C5a des-arginine. The latter is the so-called "classical" anaphylatoxin but shows no spasmogenic activity though it contains some chemotactic ability. [NIH] 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] Angiogenesis Factor: Substance causing proliferation of new blood vessels. It is found in tissues with high metabolic requirements, such as the retina, and in certain cancers. The factor is also released by hypoxic macrophages at the edges or outer surfaces of wounds and initiates revascularization in wound healing. [NIH] Angiogenesis inhibitor: A substance that may prevent the formation of blood vessels. In anticancer therapy, an angiogenesis inhibitor prevents the growth of blood vessels from surrounding tissue to a solid tumor. [NIH] Angiography: Radiography of blood vessels after injection of a contrast medium. [NIH] Angiopathy: Disease of the blood vessels (arteries, veins, and capillaries) that occurs when someone has diabetes for a long time. There are two types of angiopathy: macroangiopathy and microangiopathy. In macroangiopathy, fat and blood clots build up in the large blood vessels, stick to the vessel walls, and block the flow of blood. In microangiopathy, the walls of the smaller blood vessels become so thick and weak that they bleed, leak protein, and slow the flow of blood through the body. Then the cells, for example, the ones in the center of the eye, do not get enough blood and may be damaged. [NIH] Angiotensinogen: An alpha-globulin of which a fragment of 14 amino acids is converted by renin to angiotensin I, the inactive precursor of angiotensin II. It is a member of the serpin superfamily. [NIH] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH]
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Anomalies: Birth defects; abnormalities. [NIH] Anterior chamber: The space in front of the iris and behind the cornea. [NIH] Anterior Eye Segment: That part of the eyeball anterior to the lens. [NIH] Antiallergic: Counteracting allergy or allergic conditions. [EU] Antiangiogenesis: Prevention of the growth of new blood vessels. [NIH] Antiangiogenic: Having to do with reducing the growth of new blood vessels. [NIH] 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] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. [NIH] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] Antimetabolite: A chemical that is very similar to one required in a normal biochemical reaction in cells. Antimetabolites can stop or slow down the reaction. [NIH] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are highly reactive chemicals that often contain oxygen. They are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation. [NIH] Antithrombotic: Preventing or interfering with the formation of thrombi; an agent that so acts. [EU] Anuria: Inability to form or excrete urine. [NIH] Anus: The opening of the rectum to the outside of the body. [NIH] Aorta: The main trunk of the systemic arteries. [NIH] Aphakia: Absence of crystalline lens totally or partially from field of vision, from any cause except after cataract extraction. Aphakia is mainly congenital or as result of lens dislocation and subluxation. [NIH]
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Apolipoproteins: The protein components of lipoproteins which remain after the lipids to which the proteins are bound have been removed. They play an important role in lipid transport and metabolism. [NIH] Aponeurosis: Tendinous expansion consisting of a fibrous or membranous sheath which serves as a fascia to enclose or bind a group of muscles. [NIH] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Applicability: A list of the commodities to which the candidate method can be applied as presented or with minor modifications. [NIH] Approximate: Approximal [EU] Aqueous: Having to do with water. [NIH] Aqueous fluid: Clear, watery fluid that flows between and nourishes the lens and the cornea; secreted by the ciliary processes. [NIH] Aqueous humor: Clear, watery fluid that flows between and nourishes the lens and the cornea; secreted by the ciliary processes. [NIH] Arachidonic Acid: An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Argon: A noble gas with the atomic symbol Ar, atomic number 18, and atomic weight 39.948. It is used in fluorescent tubes and wherever an inert atmosphere is desired and nitrogen cannot be used. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arteriolar: Pertaining to or resembling arterioles. [EU] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] 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]
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Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH] Articular: Of or pertaining to a joint. [EU] Ascites: Accumulation or retention of free fluid within the peritoneal cavity. [NIH] Ascorbic Acid: A six carbon compound related to glucose. It is found naturally in citrus fruits and many vegetables. Ascorbic acid is an essential nutrient in human diets, and necessary to maintain connective tissue and bone. Its biologically active form, vitamin C, functions as a reducing agent and coenzyme in several metabolic pathways. Vitamin C is considered an antioxidant. [NIH] Aseptic: Free from infection or septic material; sterile. [EU] Aspartate: A synthetic amino acid. [NIH] Aspirin: A drug that reduces pain, fever, inflammation, and blood clotting. Aspirin belongs to the family of drugs called nonsteroidal anti-inflammatory agents. It is also being studied in cancer prevention. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Astigmatism: A condition in which the surface of the cornea is not spherical; causes a blurred image to be received at the retina. [NIH] 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] Atrial: Pertaining to an atrium. [EU] Atrial Fibrillation: Disorder of cardiac rhythm characterized by rapid, irregular atrial impulses and ineffective atrial contractions. [NIH] Atrioventricular: Pertaining to an atrium of the heart and to a ventricle. [EU] Atrium: A chamber; used in anatomical nomenclature to designate a chamber affording entrance to another structure or organ. Usually used alone to designate an atrium of the heart. [EU] Attenuation: Reduction of transmitted sound energy or its electrical equivalent. [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] Autologous: Taken from an individual's own tissues, cells, or DNA. [NIH] Axons: Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacterial Physiology: Physiological processes and activities of bacteria. [NIH] Bacterium: Microscopic organism which may have a spherical, rod-like, or spiral unicellular
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or non-cellular body. Bacteria usually reproduce through asexual processes. [NIH] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Basement Membrane: Ubiquitous supportive tissue adjacent to epithelium and around smooth and striated muscle cells. This tissue contains intrinsic macromolecular components such as collagen, laminin, and sulfated proteoglycans. As seen by light microscopy one of its subdivisions is the basal (basement) lamina. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]
Benzoic Acid: A fungistatic compound that is widely used as a food preservative. It is conjugated to glycine in the liver and excreted as hippuric acid. [NIH] Bilateral: Affecting both the right and left side of body. [NIH] Bilirubin: A bile pigment that is a degradation product of heme. [NIH] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Bioengineering: The application of engineering principles to the solution of biological problems, for example, remote-handling devices, life-support systems, controls, and displays. [NIH] Biological therapy: Treatment to stimulate or restore the ability of the immune system to fight infection and disease. Also used to lessen side effects that may be caused by some cancer treatments. Also known as immunotherapy, biotherapy, or biological response modifier (BRM) therapy. [NIH] Biological Transport: The movement of materials (including biochemical substances and drugs) across cell membranes and epithelial layers, usually by passive diffusion. [NIH] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Bladder: The organ that stores urine. [NIH] 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] Blood Cell Count: A count of the number of leukocytes and erythrocytes per unit volume in a sample of venous blood. A complete blood count (CBC) also includes measurement of the
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hemoglobin, hematocrit, and erythrocyte indices. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Coagulation Factors: Endogenous substances, usually proteins, that are involved in the blood coagulation process. [NIH] Blood Glucose: Glucose in blood. [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-Aqueous Barrier: The selectively permeable barrier between the capillary bed in the ciliary body and the aqueous humor. It consists of two layers of epithelium joined at their apical surfaces by tight junctions. [NIH] Blood-Retinal Barrier: Specialized nonfenestrated tightly-joined endothelial cells that form a transport barrier for certain substances between the retinal capillaries and the retinal tissue. [NIH] Blot: To transfer DNA, RNA, or proteins to an immobilizing matrix such as nitrocellulose. [NIH]
Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone scan: A technique to create images of bones on a computer screen or on film. A small amount of radioactive material is injected into a blood vessel and travels through the bloodstream; it collects in the bones and is detected by a scanner. [NIH] 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] Cadaver: A dead body, usually a human body. [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
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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] Callus: A callosity or hard, thick skin; the bone-like reparative substance that is formed round the edges and fragments of broken bone. [NIH] Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU] Capillary Resistance: The resistance offered to the flow of blood through the capillary portion of the peripheral vascular bed. [NIH] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Carbogen: An inhalant of oxygen and carbon dioxide that increases the sensitivity of tumor cells to the effects of radiation therapy. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinogens: Substances that increase the risk of neoplasms in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included. [NIH] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]
Cardiac: Having to do with the heart. [NIH] Cardiomyopathy: A general diagnostic term designating primary myocardial disease, often of obscure or unknown etiology. [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] Caspase: Enzyme released by the cell at a crucial stage in apoptosis in order to shred all cellular proteins. [NIH]
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Catalase: An oxidoreductase that catalyzes the conversion of hydrogen peroxide to water and oxygen. It is present in many animal cells. A deficiency of this enzyme results in acatalasia. EC 1.11.1.6. [NIH] Cataract: An opacity, partial or complete, of one or both eyes, on or in the lens or capsule, especially an opacity impairing vision or causing blindness. The many kinds of cataract are classified by their morphology (size, shape, location) or etiology (cause and time of occurrence). [EU] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [NIH] Cathode: An electrode, usually an incandescent filament of tungsten, which emits electrons in an X-ray tube. [NIH] Cations: Postively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis. [NIH] Caudal: Denoting a position more toward the cauda, or tail, than some specified point of reference; same as inferior, in human anatomy. [EU] Causal: Pertaining to a cause; directed against a cause. [EU] Cavernous Sinus: An irregularly shaped venous space in the dura mater at either side of the sphenoid bone. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Adhesion: Adherence of cells to surfaces or to other cells. [NIH] Cell Communication: Any of several ways in which living cells of an organism communicate with one another, whether by direct contact between cells or by means of chemical signals carried by neurotransmitter substances, hormones, and cyclic AMP. [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 Extracts: Preparations of cell constituents or subcellular materials, isolates, or substances. [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 motility: The ability of a cell to move. [NIH] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [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]
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Cellular adhesion: The close adherence (bonding) to adjoining cell surfaces. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Centrifugation: A method of separating organelles or large molecules that relies upon differential sedimentation through a preformed density gradient under the influence of a gravitational field generated in a centrifuge. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral Cortex: The thin layer of gray matter on the surface of the cerebral hemisphere that develops from the telencephalon and folds into gyri. It reaches its highest development in man and is responsible for intellectual faculties and higher mental functions. [NIH] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Chemotactic Factors: Chemical substances that attract or repel cells or organisms. The concept denotes especially those factors released as a result of tissue injury, invasion, or immunologic activity, that attract leukocytes, macrophages, or other cells to the site of infection or insult. [NIH] Chemotaxis: The movement of cells or organisms toward or away from a substance in response to its concentration gradient. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] 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] Chondrocytes: Polymorphic cells that form cartilage. [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 between the retina and sclera. [NIH] Choroidal Neovascularization: A pathological process consisting of the formation of new blood vessels in the choroid. [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] 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] Chylomicrons: A class of lipoproteins that carry dietary cholesterol and triglycerides from
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the small intestines to the tissues. [NIH] Ciliary: Inflammation or infection of the glands of the margins of the eyelids. [NIH] Ciliary Body: A ring of tissue extending from the scleral spur to the ora serrata of the retina. It consists of the uveal portion and the epithelial portion. The ciliary muscle is in the uveal portion and the ciliary processes are in the epithelial portion. [NIH] Ciliary processes: The extensions or projections of the ciliary body that secrete aqueous humor. [NIH] Circulatory system: The system that contains the heart and the blood vessels and moves blood throughout the body. This system helps tissues get enough oxygen and nutrients, and it helps them get rid of waste products. The lymph system, which connects with the blood system, is often considered part of the circulatory system. [NIH] Cirrhosis: A type of chronic, progressive liver disease. [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] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]
Clinical study: A research study in which patients receive treatment in a clinic or other medical facility. Reports of clinical studies can contain results for single patients (case reports) or many patients (case series or clinical trials). [NIH] Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Clot Retraction: Retraction of a clot resulting from contraction of platelet pseudopods attached to fibrin strands that is dependent on the contractile protein thrombosthenin. Used as a measure of platelet function. [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] Codons: Any triplet of nucleotides (coding unit) in DNA or RNA (if RNA is the carrier of primary genetic information as in some viruses) that codes for particular amino acid or signals the beginning or end of the message. [NIH] Coenzyme: An organic nonprotein molecule, frequently a phosphorylated derivative of a water-soluble vitamin, that binds with the protein molecule (apoenzyme) to form the active enzyme (holoenzyme). [EU] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Cohort Studies: Studies in which subsets of a defined population are identified. These groups may or may not be exposed to factors hypothesized to influence the probability of the occurrence of a particular disease or other outcome. Cohorts are defined populations
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which, as a whole, are followed in an attempt to determine distinguishing subgroup characteristics. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, 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] Colloidal: Of the nature of a colloid. [EU] Competency: The capacity of the bacterium to take up DNA from its surroundings. [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] Complement Activation: The sequential activation of serum components C1 through C9, initiated by an erythrocyte-antibody complex or by microbial polysaccharides and properdin, and producing an inflammatory response. [NIH] 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] Compliance: Distensibility measure of a chamber such as the lungs (lung compliance) or bladder. Compliance is expressed as a change in volume per unit change in pressure. [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] Computed tomography: CT scan. A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized tomography and computerized axial tomography (CAT) scan. [NIH] Computerized axial tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called CAT scan, computed tomography (CT scan), or computerized tomography. [NIH] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU] Cones: One type of specialized light-sensitive cells (photoreceptors) in the retina that provide sharp central vision and color vision. [NIH] Conjugated: Acting or operating as if joined; simultaneous. [EU] Conjunctiva: The mucous membrane that lines the inner surface of the eyelids and the anterior part of the sclera. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue Cells: A group of cells that includes fibroblasts, cartilage cells, adipocytes, smooth muscle cells, and bone cells. [NIH] Constitutional: 1. Affecting the whole constitution of the body; not local. 2. Pertaining to the constitution. [EU] Constriction: The act of constricting. [NIH] 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] Contrast medium: A substance that is introduced into or around a structure and, because of the difference in absorption of x-rays by the contrast medium and the surrounding tissues, allows radiographic visualization of the structure. [EU] Contrast Sensitivity: The ability to detect sharp boundaries (stimuli) and to detect slight changes in luminance at regions without distinct contours. Psychophysical measurements of this visual function are used to evaluate visual acuity and to detect eye disease. [NIH] Control group: In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works. [NIH] Controlled clinical trial: A clinical study that includes a comparison (control) group. The comparison group receives a placebo, another treatment, or no treatment at all. [NIH] Controlled study: An experiment or clinical trial that includes a comparison (control) group. [NIH]
Convulsions: A general term referring to sudden and often violent motor activity of cerebral or brainstem origin. Convulsions may also occur in the absence of an electrical cerebral discharge (e.g., in response to hypotension). [NIH]
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Cor: The muscular organ that maintains the circulation of the blood. c. adiposum a heart that has undergone fatty degeneration or that has an accumulation of fat around it; called also fat or fatty, heart. c. arteriosum the left side of the heart, so called because it contains oxygenated (arterial) blood. c. biloculare a congenital anomaly characterized by failure of formation of the atrial and ventricular septums, the heart having only two chambers, a single atrium and a single ventricle, and a common atrioventricular valve. c. bovinum (L. 'ox heart') a greatly enlarged heart due to a hypertrophied left ventricle; called also c. taurinum and bucardia. c. dextrum (L. 'right heart') the right atrium and ventricle. c. hirsutum, c. villosum. c. mobile (obs.) an abnormally movable heart. c. pendulum a heart so movable that it seems to be hanging by the great blood vessels. c. pseudotriloculare biatriatum a congenital cardiac anomaly in which the heart functions as a three-chambered heart because of tricuspid atresia, the right ventricle being extremely small or rudimentary and the right atrium greatly dilated. Blood passes from the right to the left atrium and thence disease due to pulmonary hypertension secondary to disease of the lung, or its blood vessels, with hypertrophy of the right ventricle. [EU] Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [NIH] Corneal Stroma: The lamellated connective tissue constituting the thickest layer of the cornea between the Bowman and Descemet membranes. [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] Corpus: The body of the uterus. [NIH] Corpus Luteum: The yellow glandular mass formed in the ovary by an ovarian follicle that has ruptured and discharged its ovum. [NIH] Corpuscle: A small mass or body; a sensory nerve end bulb; a cell, especially that of the blood or the lymph. [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]
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Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to stress. [NIH] Cortisone: A natural steroid hormone produced in the adrenal gland. It can also be made in the laboratory. Cortisone reduces swelling and can suppress immune responses. [NIH] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Creatinine: A compound that is excreted from the body in urine. Creatinine levels are measured to monitor kidney function. [NIH] Criterion: A standard by which something may be judged. [EU] Crossing-over: The exchange of corresponding segments between chromatids of homologous chromosomes during meiosia, forming a chiasma. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] Cyclosporine: A drug used to help reduce the risk of rejection of organ and bone marrow transplants by the body. It is also used in clinical trials to make cancer cells more sensitive to anticancer drugs. [NIH] Cytochrome: Any electron transfer hemoprotein having a mode of action in which the transfer of a single electron is effected by a reversible valence change of the central iron atom of the heme prosthetic group between the +2 and +3 oxidation states; classified as cytochromes a in which the heme contains a formyl side chain, cytochromes b, which contain protoheme or a closely similar heme that is not covalently bound to the protein, cytochromes c in which protoheme or other heme is covalently bound to the protein, and cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the hemes have. Well-known cytochromes have been numbered consecutively within groups and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, . New cytochromes are named according to the wavelength in nanometres of the absorption maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. [NIH] Cytostatic: An agent that suppresses cell growth and multiplication. [EU] Cytotoxic: Cell-killing. [NIH] Dark Adaptation: Adjustment of the eyes under conditions of low light. The sensitivity of the eye to light is increased during dark adaptation. [NIH] Daunorubicin: Very toxic anthracycline aminoglycoside antibiotic isolated from Streptomyces peucetius and others, used in treatment of leukemias and other neoplasms. [NIH]
Decidua: The epithelial lining of the endometrium that is formed before the fertilized ovum reaches the uterus. The fertilized ovum embeds in the decidua. If the ovum is not fertilized, the decidua is shed during menstruation. [NIH] Defense Mechanisms: Unconscious process used by an individual or a group of individuals
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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] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Delivery of Health Care: The concept concerned with all aspects of providing and distributing health services to a patient population. [NIH] 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] 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] Deprivation: Loss or absence of parts, organs, powers, or things that are needed. [EU] Depth Perception: Perception of three-dimensionality. [NIH] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] Developed Countries: Countries that have reached a level of economic achievement through an increase of production, per capita income and consumption, and utilization of natural and human resources. [NIH] Dexamethasone: (11 beta,16 alpha)-9-Fluoro-11,17,21-trihydroxy-16-methylpregna-1,4diene-3,20-dione. An anti-inflammatory glucocorticoid used either in the free alcohol or esterified form in treatment of conditions that respond generally to cortisone. [NIH] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diagnostic Services: Organized services for the purpose of providing diagnosis to promote and maintain health. [NIH] Diaphragm: The musculofibrous partition that separates the thoracic cavity from the abdominal cavity. Contraction of the diaphragm increases the volume of the thoracic cavity aiding inspiration. [NIH] Diastole: Period of relaxation of the heart, especially the ventricles. [NIH] Diastolic: Of or pertaining to the diastole. [EU] Diastolic blood pressure: The minimum pressure that remains within the artery when the heart is at rest. [NIH] 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 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] Digital photography: A type of photography in which images can be viewed on a computer screen. [NIH]
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Dihydrotestosterone: Anabolic agent. [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] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Discrete: Made up of separate parts or characterized by lesions which do not become blended; not running together; separate. [NIH] Discrimination: The act of qualitative and/or quantitative differentiation between two or more stimuli. [NIH] Disease Progression: The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis. [NIH] Disparity: Failure of the two retinal images of an object to fall on corresponding retinal points. [NIH] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] 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] Diuretic: A drug that increases the production of urine. [NIH] Dominance: In genetics, the full phenotypic expression of a gene in both heterozygotes and homozygotes. [EU] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] Dorsal: 1. Pertaining to the back or to any dorsum. 2. Denoting a position more toward the back surface than some other object of reference; same as posterior in human anatomy; superior in the anatomy of quadrupeds. [EU] Dorsum: A plate of bone which forms the posterior boundary of the sella turcica. [NIH] Double-blind: Pertaining to a clinical trial or other experiment in which neither the subject nor the person administering treatment knows which treatment any particular subject is receiving. [EU] Doxorubicin: Antineoplastic antibiotic obtained from Streptomyces peucetics. It is a hydroxy derivative of daunorubicin and is used in treatment of both leukemia and solid tumors. [NIH] Drive: A state of internal activity of an organism that is a necessary condition before a given
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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 Delivery Systems: Systems of administering drugs through controlled delivery so that an optimum amount reaches the target site. Drug delivery systems encompass the carrier, route, and target. [NIH] Drug Design: The molecular designing of drugs for specific purposes (such as DNAbinding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include pharmacokinetics, dosage analysis, or drug administration analysis. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] Duodenum: The first part of the small intestine. [NIH] Dyslipidemia: Disorders in the lipoprotein metabolism; classified as hypercholesterolemia, hypertriglyceridemia, combined hyperlipidemia, and low levels of high-density lipoprotein (HDL) cholesterol. All of the dyslipidemias can be primary or secondary. Both elevated levels of low-density lipoprotein (LDL) cholesterol and low levels of HDL cholesterol predispose to premature atherosclerosis. [NIH] Dyspnea: Difficult or labored breathing. [NIH] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] Eclampsia: Onset of convulsions or coma in a previously diagnosed pre-eclamptic patient. [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] 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] Eicosanoids: A class of oxygenated, endogenous, unsaturated fatty acids derived from arachidonic acid. They include prostaglandins, leukotrienes, thromboxanes, and hydroxyeicosatetraenoic acid compounds (HETE). They are hormone-like substances that act near the site of synthesis without altering functions throughout the body. [NIH] Elasticity: Resistance and recovery from distortion of shape. [NIH] Elastin: The protein that gives flexibility to tissues. [NIH] Electrolysis: Destruction by passage of a galvanic electric current, as in disintegration of a chemical compound in solution. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU]
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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] Electroretinogram: The electrical effect recorded from the surface of the eyeball and originated by a pulse of light. [NIH] 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] Emboli: Bit of foreign matter which enters the blood stream at one point and is carried until it is lodged or impacted in an artery and obstructs it. It may be a blood clot, an air bubble, fat or other tissue, or clumps of bacteria. [NIH] Embolism: Blocking of a blood vessel by a blood clot or foreign matter that has been transported from a distant site by the blood stream. [NIH] Embolization: The blocking of an artery by a clot or foreign material. Embolization can be done as treatment to block the flow of blood to a tumor. [NIH] Embolus: Bit of foreign matter which enters the blood stream at one point and is carried until it is lodged or impacted in an artery and obstructs it. It may be a blood clot, an air bubble, fat or other tissue, or clumps of bacteria. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] 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] Empirical: A treatment based on an assumed diagnosis, prior to receiving confirmatory laboratory test results. [NIH] Enalapril: An angiotensin-converting enzyme inhibitor that is used to treat hypertension. [NIH]
Endoderm: The inner of the three germ layers of the embryo. [NIH] Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [NIH] Endometrium: The layer of tissue that lines the uterus. [NIH] Endonucleases: Enzymes that catalyze the hydrolysis of the internal bonds and thereby the formation of polynucleotides or oligonucleotides from ribo- or deoxyribonucleotide chains. EC 3.1.-. [NIH] Endophthalmitis: Suppurative inflammation of the tissues of the internal structures of the eye; not all layers of the uvea are affected. Fungi, necrosis of intraocular tumors, and retained intraocular foreign bodies often cause a purulent endophthalmitis. [NIH] Endorphins: One of the three major groups of endogenous opioid peptides. They are large peptides derived from the pro-opiomelanocortin precursor. The known members of this group are alpha-, beta-, and gamma-endorphin. The term endorphin is also sometimes used to refer to all opioid peptides, but the narrower sense is used here; opioid peptides is used for the broader group. [NIH]
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Endostatin: A drug that is being studied for its ability to prevent the growth of new blood vessels into a solid tumor. Endostatin belongs to the family of drugs called angiogenesis inhibitors. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium, Lymphatic: Unbroken cellular lining (intima) of the lymph vessels (e.g., the high endothelial lymphatic venules). It is more permeable than vascular endothelium, lacking selective absorption and functioning mainly to remove plasma proteins that have filtered through the capillaries into the tissue spaces. [NIH] Endothelium, Vascular: Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components from interstitium to lumen; this function has been most intensively studied in the blood capillaries. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] Endotoxins: Toxins closely associated with the living cytoplasm or cell wall of certain microorganisms, which do not readily diffuse into the culture medium, but are released upon lysis of the cells. [NIH] End-stage renal: Total chronic kidney failure. When the kidneys fail, the body retains fluid and harmful wastes build up. A person with ESRD needs treatment to replace the work of the failed kidneys. [NIH] Energy balance: Energy is the capacity of a body or a physical system for doing work. Energy balance is the state in which the total energy intake equals total energy needs. [NIH] Enkephalins: One of the three major families of endogenous opioid peptides. The enkephalins are pentapeptides that are widespread in the central and peripheral nervous systems and in the adrenal medulla. [NIH] Enteropeptidase: A specialized proteolytic enzyme secreted by intestinal cells. It converts trypsinogen into its active form trypsin by removing the N-terminal peptide. EC 3.4.21.9. [NIH]
Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]
Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Epidemic: Occurring suddenly in numbers clearly in excess of normal expectancy; said especially of infectious diseases but applied also to any disease, injury, or other healthrelated event occurring in such outbreaks. [EU] Epidemiological: Relating to, or involving epidemiology. [EU] Epigastric: Having to do with the upper middle area of the abdomen. [NIH] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH]
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Epiretinal Membrane: Membrane viruses are thought to acquire their envelopes by budding through modified portions of the host cell membrane. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Erectile: The inability to get or maintain an erection for satisfactory sexual intercourse. Also called impotence. [NIH] Erection: The condition of being made rigid and elevated; as erectile tissue when filled with blood. [EU] Erythrocyte Membrane: The semipermeable outer portion of the red corpuscle. It is known as a 'ghost' after hemolysis. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]
Estrogen: One of the two female sex hormones. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Evoke: The electric response recorded from the cerebral cortex after stimulation of a peripheral sense organ. [NIH] Excitability: Property of a cardiac cell whereby, when the cell is depolarized to a critical level (called threshold), the membrane becomes permeable and a regenerative inward current causes an action potential. [NIH] Excitation: An act of irritation or stimulation or of responding to a stimulus; the addition of energy, as the excitation of a molecule by absorption of photons. [EU] Excitatory: When cortical neurons are excited, their output increases and each new input they receive while they are still excited raises their output markedly. [NIH] Excrete: To get rid of waste from the body. [NIH] Exocrine: Secreting outwardly, via a duct. [EU] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Exon: The part of the DNA that encodes the information for the actual amino acid sequence of the protein. In many eucaryotic genes, the coding sequences consist of a series of exons alternating with intron sequences. [NIH] Expiration: The act of breathing out, or expelling air from the lungs. [EU] Expiratory: The volume of air which leaves the breathing organs in each expiration. [NIH] Extensor: A muscle whose contraction tends to straighten a limb; the antagonist of a flexor. [NIH]
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
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dishes adhere. [NIH] Extracellular Matrix Proteins: Macromolecular organic compounds that contain carbon, hydrogen, oxygen, nitrogen, and usually, sulfur. These macromolecules (proteins) form an intricate meshwork in which cells are embedded to construct tissues. Variations in the relative types of macromolecules and their organization determine the type of extracellular matrix, each adapted to the functional requirements of the tissue. The two main classes of macromolecules that form the extracellular matrix are: glycosaminoglycans, usually linked to proteins (proteoglycans), and fibrous proteins (e.g., collagen, elastin, fibronectins and laminin). [NIH] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] Extraction: The process or act of pulling or drawing out. [EU] Extrapyramidal: Outside of the pyramidal tracts. [EU] Eye Infections: Infection, moderate to severe, caused by bacteria, fungi, or viruses, which occurs either on the external surface of the eye or intraocularly with probable inflammation, visual impairment, or blindness. [NIH] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] Fatty acids: A major component of fats that are used by the body for energy and tissue development. [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] Fibroblast Growth Factor: Peptide isolated from the pituitary gland and from the brain. It is a potent mitogen which stimulates growth of a variety of mesodermal cells including chondrocytes, granulosa, and endothelial cells. The peptide may be active in wound healing and animal limb regeneration. [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibronectin: An adhesive glycoprotein. One form circulates in plasma, acting as an opsonin; another is a cell-surface protein which mediates cellular adhesive interactions. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Fluorescein Angiography: Visualization of a vascular system after intravenous injection of a fluorescein solution. The images may be photographed or televised. It is used especially in studying the retinal and uveal vasculature. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Fovea: The central part of the macula that provides the sharpest vision. [NIH]
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Free Radicals: Highly reactive molecules with an unsatisfied electron valence pair. Free radicals are produced in both normal and pathological processes. They are proven or suspected agents of tissue damage in a wide variety of circumstances including radiation, damage from environment chemicals, and aging. Natural and pharmacological prevention of free radical damage is being actively investigated. [NIH] 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]
Fundus: The larger part of a hollow organ that is farthest away from the organ's opening. The bladder, gallbladder, stomach, uterus, eye, and cavity of the middle ear all have a fundus. [NIH] Fungistatic: Inhibiting the growth of fungi. [EU] Galactitol: A naturally occurring product of plants obtained following reduction of galactose. It appears as a white crystalline powder with a slight sweet taste. It may form in excess in the lens of the eye in galactosemia, a deficiency of galactokinase. [NIH] Galactokinase: An enzyme that catalyzes reversibly the formation of galactose 1-phosphate and ADP from ATP and D-galactose. Galactosamine can also act as the acceptor. A deficiency of this enzyme results in galactosemia. EC 2.7.1.6. [NIH] Galactosemia: Buildup of galactose in the blood. Caused by lack of one of the enzymes needed to break down galactose into glucose. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gamma-interferon: Interferon produced by T-lymphocytes in response to various mitogens and antigens. Gamma interferon appears to have potent antineoplastic, immunoregulatory and antiviral activity. [NIH] Ganglion: 1. A knot, or knotlike mass. 2. A general term for a group of nerve cell bodies located outside the central nervous system; occasionally applied to certain nuclear groups within the brain or spinal cord, e.g. basal ganglia. 3. A benign cystic tumour occurring on a aponeurosis or tendon, as in the wrist or dorsum of the foot; it consists of a thin fibrous capsule enclosing a clear mucinous fluid. [EU] 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] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]
Gastrointestinal: Refers to the stomach and intestines. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]
Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Gene Expression Profiling: The determination of the pattern of genes expressed i.e., transcribed, under specific circumstances or in a specific cell. [NIH] Gene Therapy: The introduction of new genes into cells for the purpose of treating disease by restoring or adding gene expression. Techniques include insertion of retroviral vectors, transfection, homologous recombination, and injection of new genes into the nuclei of single cell embryos. The entire gene therapy process may consist of multiple steps. The new genes
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may be introduced into proliferating cells in vivo (e.g., bone marrow) or in vitro (e.g., fibroblast cultures) and the modified cells transferred to the site where the gene expression is required. Gene therapy may be particularly useful for treating enzyme deficiency diseases, hemoglobinopathies, and leukemias and may also prove useful in restoring drug sensitivity, particularly for leukemia. [NIH] Genetic 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] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Germ Cells: The reproductive cells in multicellular organisms. [NIH] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] Gestational: Psychosis attributable to or occurring during pregnancy. [NIH] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus. [EU]
Glomerular Filtration Rate: The volume of water filtered out of plasma through glomerular capillary walls into Bowman's capsules per unit of time. It is considered to be equivalent to inulin clearance. [NIH] Glomeruli: Plural of glomerulus. [NIH] Glomerulosclerosis: Scarring of the glomeruli. It may result from diabetes mellitus (diabetic glomerulosclerosis) or from deposits in parts of the glomerulus (focal segmental glomerulosclerosis). The most common signs of glomerulosclerosis are proteinuria and kidney failure. [NIH] Glomerulus: A tiny set of looping blood vessels in the nephron where blood is filtered in the kidney. [NIH] Glucocorticoid: A compound that belongs to the family of compounds called corticosteroids (steroids). Glucocorticoids affect metabolism and have anti-inflammatory and immunosuppressive effects. They may be naturally produced (hormones) or synthetic (drugs). [NIH] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glucose Intolerance: A pathological state in which the fasting plasma glucose level is less than 140 mg per deciliter and the 30-, 60-, or 90-minute plasma glucose concentration following a glucose tolerance test exceeds 200 mg per deciliter. This condition is seen frequently in diabetes mellitus but also occurs with other diseases. [NIH] Glucose tolerance: The power of the normal liver to absorb and store large quantities of glucose and the effectiveness of intestinal absorption of glucose. The glucose tolerance test is a metabolic test of carbohydrate tolerance that measures active insulin, a hepatic function based on the ability of the liver to absorb glucose. The test consists of ingesting 100 grams of glucose into a fasting stomach; blood sugar should return to normal in 2 to 21 hours after ingestion. [NIH]
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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] 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]
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]
Glycerophospholipids: Derivatives of phosphatidic acid in which the hydrophobic regions are composed of two fatty acids and a polar alcohol is joined to the C-3 position of glycerol through a phosphodiester bond. They are named according to their polar head groups, such as phosphatidylcholine and phosphatidylethanolamine. [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] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] 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] Grading: A system for classifying cancer cells in terms of how abnormal they appear when examined under a microscope. The objective of a grading system is to provide information about the probable growth rate of the tumor and its tendency to spread. The systems used to grade tumors vary with each type of cancer. Grading plays a role in treatment decisions. [NIH]
Grafting: The operation of transfer of tissue from one site to another. [NIH] Granule: A small pill made from sucrose. [EU] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Growth factors: Substances made by the body that function to regulate cell division and cell survival. Some growth factors are also produced in the laboratory and used in biological therapy. [NIH] Guanylate Cyclase: An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2. [NIH] Haematoma: A localized collection of blood, usually clotted, in an organ, space, or tissue, due to a break in the wall of a blood vessel. [EU] Haemorrhage: The escape of blood from the vessels; bleeding. Small haemorrhages are classified according to size as petechiae (very small), purpura (up to 1 cm), and ecchymoses (larger). The massive accumulation of blood within a tissue is called a haematoma. [EU] 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
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as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Health Care Costs: The actual costs of providing services related to the delivery of health care, including the costs of procedures, therapies, and medications. It is differentiated from health expenditures, which refers to the amount of money paid for the services, and from fees, which refers to the amount charged, regardless of cost. [NIH] Health Education: Education that increases the awareness and favorably influences the attitudes and knowledge relating to the improvement of health on a personal or community basis. [NIH] Health Expenditures: The amounts spent by individuals, groups, nations, or private or public organizations for total health care and/or its various components. These amounts may or may not be equivalent to the actual costs (health care costs) and may or may not be shared among the patient, insurers, and/or employers. [NIH] Health Services: Services for the diagnosis and treatment of disease and the maintenance of health. [NIH] 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] Hematocrit: Measurement of the volume of packed red cells in a blood specimen by centrifugation. The procedure is performed using a tube with graduated markings or with automated blood cell counters. It is used as an indicator of erythrocyte status in disease. For example, anemia shows a low hematocrit, polycythemia, high values. [NIH] Hematopoiesis: The development and formation of various types of blood cells. [NIH] Hemochromatosis: A disease that occurs when the body absorbs too much iron. The body stores the excess iron in the liver, pancreas, and other organs. May cause cirrhosis of the liver. Also called iron overload disease. [NIH] Hemodialysis: The use of a machine to clean wastes from the blood after the kidneys have failed. The blood travels through tubes to a dialyzer, which removes wastes and extra fluid. The cleaned blood then flows through another set of tubes back into the body. [NIH] Hemodynamics: The movements of the blood and the forces involved in systemic or regional blood circulation. [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] Hemoglobinopathies: A group of inherited disorders characterized by structural alterations within the hemoglobin molecule. [NIH] Hemolysis: The destruction of erythrocytes by many different causal agents such as
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antibodies, bacteria, chemicals, temperature, and changes in tonicity. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemostasis: The process which spontaneously arrests the flow of blood from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation. [NIH]
Heparan Sulfate Proteoglycan: A substance released by astrocytes, which is critical in stopping nervous fibers in their tracks. [NIH] Hepatic: Refers to the liver. [NIH] Hepatocyte: A liver cell. [NIH] Hepatocyte Growth Factor: Multifunctional growth factor which regulates both cell growth and cell motility. It exerts a strong mitogenic effect on hepatocytes and primary epithelial cells. Its receptor is proto-oncogene protein C-met. [NIH] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Heterodimer: 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]
Heterozygotes: Having unlike alleles at one or more corresponding loci on homologous chromosomes. [NIH] Histology: The study of tissues and cells under a microscope. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Homogeneous: Consisting of or composed of similar elements or ingredients; of a uniform quality throughout. [EU] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Homozygotes: An individual having a homozygous gene pair. [NIH] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] 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] 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
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isotope tritium. [NIH] Hydrogen Peroxide: A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] 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] Hypercholesterolemia: Abnormally high levels of cholesterol in the blood. [NIH] Hyperglycemia: Abnormally high blood sugar. [NIH] Hyperlipidemia: An excess of lipids in the blood. [NIH] Hyperopia: Farsightedness; ability to see distant objects more clearly than close objects; may be corrected with glasses or contact lenses. [NIH] Hyperoxia: An abnormal increase in the amount of oxygen in the tissues and organs. [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] Hypertrophy: General increase in bulk of a part or organ, not due to tumor formation, nor to an increase in the number of cells. [NIH] Hypesthesia: Absent or reduced sensitivity to cutaneous stimulation. [NIH] Hypoglycemia: Abnormally low blood sugar [NIH] Hypoglycemic: An orally active drug that produces a fall in blood glucose concentration. [NIH]
Hypoglycemic Agents: Agents which lower the blood glucose level. [NIH] Hypotension: Abnormally low blood pressure. [NIH] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU] Hypoxic: Having too little oxygen. [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
Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents. [NIH]
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Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunology: The study of the body's immune system. [NIH] Immunomodulator: New type of drugs mainly using biotechnological methods. Treatment of cancer. [NIH] Immunosuppressant: An agent capable of suppressing immune responses. [EU] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Implant radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called [NIH] Implantation: The insertion or grafting into the body of biological, living, inert, or radioactive material. [EU] Impotence: The inability to perform sexual intercourse. [NIH] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes. [NIH] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH] Incontinence: Inability to control the flow of urine from the bladder (urinary incontinence) or the escape of stool from the rectum (fecal incontinence). [NIH] Incubation: The development of an infectious disease from the entrance of the pathogen to the appearance of clinical symptoms. [EU] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infancy: The period of complete dependency prior to the acquisition of competence in walking, talking, and self-feeding. [NIH] Infantile: Pertaining to an infant or to infancy. [EU] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]
Infiltration: The diffusion or accumulation in a tissue or cells of substances not normal to it
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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] Informed Consent: Voluntary authorization, given to the physician by the patient, with full comprehension of the risks involved, for diagnostic or investigative procedures and medical and surgical treatment. [NIH] Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Ingestion: Taking into the body by mouth [NIH] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Initiator: A chemically reactive substance which may cause cell changes if ingested, inhaled or absorbed into the body; the substance may thus initiate a carcinogenic process. [NIH] Inner ear: The labyrinth, comprising the vestibule, cochlea, and semicircular canals. [NIH] 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] 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] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune, genetic, and environmental factors are involved in the development of type I diabetes. [NIH] Insulin-like: Muscular growth factor. [NIH] 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] Intercellular Adhesion Molecule-1: A cell-surface ligand with a role in leukocyte adhesion and inflammation. Its production is induced by gamma-interferon and it is required for neutrophil migration into inflamed tissue. [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
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laboratory for use in treating cancer and other diseases. [NIH] Interleukin-1: A soluble factor produced by monocytes, macrophages, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. IL-1 consists of two distinct forms, IL-1 alpha and IL-1 beta which perform the same functions but are distinct proteins. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation. The factor is distinct from interleukin-2. [NIH] Interleukin-12: A heterodimeric cytokine that stimulates the production of interferon gamma from T-cells and natural killer cells, and also induces differentiation of Th1 helper cells. It is an initiator of cell-mediated immunity. [NIH] Interleukin-2: Chemical mediator produced by activated T lymphocytes and which regulates the proliferation of T cells, as well as playing a role in the regulation of NK cell activity. [NIH] Interleukin-6: Factor that stimulates the growth and differentiation of human B-cells and is also a growth factor for hybridomas and plasmacytomas. It is produced by many different cells including T-cells, monocytes, and fibroblasts. [NIH] 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] Intervention Studies: Epidemiologic investigations designed to test a hypothesized causeeffect relation by modifying the supposed causal factor(s) in the study population. [NIH] Intestinal: Having to do with the intestines. [NIH] Intestinal Mucosa: The surface lining of the intestines where the cells absorb nutrients. [NIH] Intestines: The section of the alimentary canal from the stomach to the anus. It includes the large intestine and small intestine. [NIH] Intracellular: Inside a cell. [NIH] Intramuscular: IM. Within or into muscle. [NIH] Intraocular: Within the eye. [EU] Intraocular pressure: Pressure of the fluid inside the eye; normal IOP varies among individuals. [NIH] Intravascular: Within a vessel or vessels. [EU] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Inulin: A starch found in the tubers and roots of many plants. Since it is hydrolyzable to fructose, it is classified as a fructosan. It has been used in physiologic investigation for determination of the rate of glomerular function. [NIH] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]
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
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neurotransmitter receptors are not included. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Iridis: The angle between the iris and the cornea at the periphery of the anterior chamber of the eye. [NIH] Iris: The most anterior portion of the uveal layer, separating the anterior chamber from the posterior. It consists of two layers - the stroma and the pigmented epithelium. Color of the iris depends on the amount of melanin in the stroma on reflection from the pigmented epithelium. [NIH] 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 substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Irradiation is also called radiation therapy, radiotherapy, and x-ray therapy. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] 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] Keto: It consists of 8 carbon atoms and within the endotoxins, it connects poysaccharide and lipid A. [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 Transplantation: The transference of a kidney from one human or animal to another. [NIH] Kinetic: Pertaining to or producing motion. [EU] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU]
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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] Laser Coagulation: The coagulation of tissues using lasers. These lasers produce light in the visible green wavelength that is selectively absorbed by hemoglobin, and thus it is possible to seal bleeding blood vessels. [NIH] Laser Surgery: The use of a laser either to vaporize surface lesions or to make bloodless cuts in tissue. It does not include the coagulation of tissue by laser. [NIH] Laser therapy: The use of an intensely powerful beam of light to kill cancer cells. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Laxative: An agent that acts to promote evacuation of the bowel; a cathartic or purgative. [EU]
Least-Squares Analysis: A principle of estimation in which the estimates of a set of parameters in a statistical model are those quantities minimizing the sum of squared differences between the observed values of a dependent variable and the values predicted by the model. [NIH] Lens: The transparent, double convex (outward curve on both sides) structure suspended between the aqueous and vitreous; helps to focus light on the retina. [NIH] Leptin: A 16-kD peptide hormone secreted from white adipocytes and implicated in the regulation of food intake and energy balance. Leptin provides the key afferent signal from fat cells in the feedback system that controls body fat stores. [NIH] Lesion: An area of abnormal tissue change. [NIH] Lethal: Deadly, fatal. [EU] Leukemia: Cancer of blood-forming tissue. [NIH] Leukemic Infiltration: A pathologic change in leukemia in which leukemic cells permeate various organs at any stage of the disease. All types of leukemia show various degrees of infiltration, depending upon the type of leukemia. The degree of infiltration may vary from site to site. The liver and spleen are common sites of infiltration, the greatest appearing in myelocytic leukemia, but infiltration is seen also in the granulocytic and lymphocytic types. The kidney is also a common site and of the gastrointestinal system, the stomach and ileum are commonly involved. In lymphocytic leukemia the skin is often infiltrated. The central nervous system too is a common site. [NIH] Leukostasis: Abnormal intravascular leukocyte aggregation and clumping often seen in leukemia patients. The brain and lungs are the two most commonly affected organs. This acute syndrome requires aggressive cytoreductive modalities including chemotherapy and/or leukophoresis. It is differentiated from leukemic infiltration which is a neoplastic process where leukemic cells invade organs. [NIH] Leukotrienes: A family of biologically active compounds derived from arachidonic acid by oxidative metabolism through the 5-lipoxygenase pathway. They participate in host defense reactions and pathophysiological conditions such as immediate hypersensitivity and inflammation. They have potent actions on many essential organs and systems, including the cardiovascular, pulmonary, and central nervous system as well as the gastrointestinal
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tract and the immune system. [NIH] Ligaments: Shiny, flexible bands of fibrous tissue connecting together articular extremities of bones. They are pliant, tough, and inextensile. [NIH] Ligands: A RNA simulation method developed by the MIT. [NIH] Light microscope: A microscope (device to magnify small objects) in which objects are lit directly by white light. [NIH] Likelihood Functions: Functions constructed from a statistical model and a set of observed data which give the probability of that data for various values of the unknown model parameters. Those parameter values that maximize the probability are the maximum likelihood estimates of the parameters. [NIH] Linear Models: Statistical models in which the value of a parameter for a given value of a factor is assumed to be equal to a + bx, where a and b are constants. The models predict a linear regression. [NIH] Linkage: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Lipid: Fat. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] Lipophilic: Having an affinity for fat; pertaining to or characterized by lipophilia. [EU] 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] Lipoprotein(a): A family of lipoprotein particles varying in density and size depending on the protein-lipid ratio and the protein composition. These particles consist of apolipoprotein B-100 covalently linked to apolipoprotein-a by one or two disulfide bonds. There is a correlation between high plasma levels of this lipoprotein and increased risk for atherosclerotic cardiovascular disease. [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 scan: An image of the liver created on a computer screen or on film. A radioactive substance is injected into a blood vessel and travels through the bloodstream. It collects in the liver, especially in abnormal areas, and can be detected by the scanner. [NIH] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Logistic Models: Statistical models which describe the relationship between a qualitative dependent variable (that is, one which can take only certain discrete values, such as the presence or absence of a disease) and an independent variable. A common application is in epidemiology for estimating an individual's risk (probability of a disease) as a function of a given risk factor. [NIH] Longitudinal Studies: Studies in which variables relating to an individual or group of individuals are assessed over a period of time. [NIH]
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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 vision: Visual loss that cannot be corrected with eyeglasses or contact lenses and interferes with daily living activities. [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] Lucida: An instrument, invented by Wollaton, consisting essentially of a prism or a mirror through which an object can be viewed so as to appear on a plane surface seen in direct view and on which the outline of the object may be traced. [NIH] Luciferase: Any one of several enzymes that catalyze the bioluminescent reaction in certain marine crustaceans, fish, bacteria, and insects. The enzyme is a flavoprotein; it oxidizes luciferins to an electronically excited compound that emits energy in the form of light. The color of light emitted varies with the organism. The firefly enzyme is a valuable reagent for measurement of ATP concentration. (Dorland, 27th ed) EC 1.13.12.-. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] 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] Lymphocytes: White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each); those with characteristics of neither major class are called null cells. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lysine: An essential amino acid. It is often added to animal feed. [NIH] Lysophospholipids: Derivatives of phosphatidic acids that lack one of its fatty acyl chains due to its hydrolytic removal. [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
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clinical applications such as NMR Tomography (magnetic resonance imaging). [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] Mammogram: An x-ray of the breast. [NIH] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] Matrix metalloproteinase: A member of a group of enzymes that can break down proteins, such as collagen, that are normally found in the spaces between cells in tissues (i.e., extracellular matrix proteins). Because these enzymes need zinc or calcium atoms to work properly, they are called metalloproteinases. Matrix metalloproteinases are involved in wound healing, angiogenesis, and tumor cell metastasis. [NIH] 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] 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 store in the pigment containing organelles called melanosomes. Melanophores are larger cells which do not exist in mammals. [NIH] Melanoma: A form of skin cancer that arises in melanocytes, the cells that produce pigment. Melanoma usually begins in a mole. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Lipids: Lipids, predominantly phospholipids, cholesterol and small amounts of glycolipids found in membranes including cellular and intracellular membranes. These lipids may be arranged in bilayers in the membranes with integral proteins between the layers and peripheral proteins attached to the outside. Membrane lipids are required for active transport, several enzymatic activities and membrane formation. [NIH] Menorrhagia: Excessive menstrual flow. [NIH] Menstruation: The normal physiologic discharge through the vagina of blood and mucosal tissues from the nonpregnant uterus. [NIH]
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Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] Mental Health: The state wherein the person is well adjusted. [NIH] Mesenchymal: Refers to cells that develop into connective tissue, blood vessels, and lymphatic tissue. [NIH] Mesoderm: The middle germ layer of the embryo. [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] Metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors" and contain cells that are like those in the original (primary) tumor. The plural is metastases. [NIH] Metastatic: Having to do with metastasis, which is the spread of cancer from one part of the body to another. [NIH] Metastatic cancer: Cancer that has spread from the place in which it started to other parts of the body. [NIH] Methotrexate: An antineoplastic antimetabolite with immunosuppressant properties. It is an inhibitor of dihydrofolate reductase and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA. [NIH] Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated egg or embryo. The technique involves microinjection of DNA fragments from another species into the nucleus of the fertilized egg. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microcalcifications: Tiny deposits of calcium in the breast that cannot be felt but can be detected on a mammogram. A cluster of these very small specks of calcium may indicate that cancer is present. [NIH] Microcirculation: The vascular network lying between the arterioles and venules; includes capillaries, metarterioles and arteriovenous anastomoses. Also, the flow of blood through this network. [NIH] Microglia: The third type of glial cell, along with astrocytes and oligodendrocytes (which together form the macroglia). Microglia vary in appearance depending on developmental stage, functional state, and anatomical location; subtype terms include ramified, perivascular, ameboid, resting, and activated. Microglia clearly are capable of phagocytosis and play an important role in a wide spectrum of neuropathologies. They have also been suggested to act in several other roles including in secretion (e.g., of cytokines and neural growth factors), in immunological processing (e.g., antigen presentation), and in central nervous system development and remodeling. [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] Microsurgery: Surgical procedures on the cellular level; a light microscope and miniaturized instruments are used. [NIH]
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Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [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] 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] Mobility: Capability of movement, of being moved, or of flowing freely. [EU] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Modulator: A specific inductor that brings out characteristics peculiar to a definite region. [EU]
Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] 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] Mononuclear: A cell with one nucleus. [NIH] Morphological: Relating to the configuration or the structure of live organs. [NIH] Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Motility: The ability to move spontaneously. [EU] Mucinous: Containing or resembling mucin, the main compound in mucus. [NIH] Multiple sclerosis: A disorder of the central nervous system marked by weakness, numbness, a loss of muscle coordination, and problems with vision, speech, and bladder control. Multiple sclerosis is thought to be an autoimmune disease in which the body's immune system destroys myelin. Myelin is a substance that contains both protein and fat (lipid) and serves as a nerve insulator and helps in the transmission of nerve signals. [NIH] Mutagenesis: Process of generating genetic mutations. It may occur spontaneously or be induced by mutagens. [NIH] Mutagens: Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in
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chromosomes. [NIH] Mydriatic: 1. Dilating the pupil. 2. Any drug that dilates the pupil. [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 known as cardiac muscle. [NIH] Myopia: That error of refraction in which rays of light entering the eye parallel to the optic axis are brought to a focus in front of the retina, as a result of the eyeball being too long from front to back (axial m.) or of an increased strength in refractive power of the media of the eye (index m.). Called also nearsightedness, because the near point is less distant than it is in emmetropia with an equal amplitude of accommodation. [EU] Natural killer cells: NK cells. A type of white blood cell that contains granules with enzymes that can kill tumor cells or microbial cells. Also called large granular lymphocytes (LGL). [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] 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 Processes: The pathological mechanisms and forms taken by tissue during degeneration into a neoplasm and its subsequent activity. [NIH] Nephropathy: Disease of the kidneys. [EU] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Networks: Pertaining to a nerve or to the nerves, a meshlike structure of interlocking fibers or strands. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neuritis: A general term indicating inflammation of a peripheral or cranial nerve. Clinical manifestation may include pain; paresthesias; paresis; or hypesthesia. [NIH] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neuropathy: A problem in any part of the nervous system except the brain and spinal cord.
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Neuropathies can be caused by infection, toxic substances, or disease. [NIH] Neuroretinitis: Inflammation of the optic nerve head and adjacent retina. [NIH] Neurotoxin: A substance that is poisonous to nerve tissue. [NIH] Neurotransmitter: Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel across the synaptic cleft to either excite or inhibit the target cell. Among the many substances that have the properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic acid, substance P, enkephalins, endorphins, and serotonin. [EU] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] Neutrophil: A type of white blood cell. [NIH] Night Blindness: Anomaly of vision in which there is a pronounced inadequacy or complete absence of dark-adaptation. [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] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Observational study: An epidemiologic study that does not involve any intervention, experimental or otherwise. Such a study may be one in which nature is allowed to take its course, with changes in one characteristic being studied in relation to changes in other
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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] Occult: Obscure; concealed from observation, difficult to understand. [EU] Ocular: 1. Of, pertaining to, or affecting the eye. 2. Eyepiece. [EU] Ocular Hypertension: A condition in which the intraocular pressure is elevated above normal and which may lead to glaucoma. [NIH] Oedema: The presence of abnormally large amounts of fluid in the intercellular tissue spaces of the body; usually applied to demonstrable accumulation of excessive fluid in the subcutaneous tissues. Edema may be localized, due to venous or lymphatic obstruction or to increased vascular permeability, or it may be systemic due to heart failure or renal disease. Collections of edema fluid are designated according to the site, e.g. ascites (peritoneal cavity), hydrothorax (pleural cavity), and hydropericardium (pericardial sac). Massive generalized edema is called anasarca. [EU] Oligo: Chemical and mineral elements that exist in minimal (oligo) quantities in the body, in foods, in the air, in soil; name applied to any element observed as a microconstituent of plant or animal tissue and of beneficial, harmful, or even doubtful significance. [NIH] Oliguria: Clinical manifestation of the urinary system consisting of a decrease in the amount of urine secreted. [NIH] Omega-3 fatty acid: A type of fat obtained in the diet and involved in immunity. [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] Open Reading Frames: Reading frames where successive nucleotide triplets can be read as codons specifying amino acids and where the sequence of these triplets is not interrupted by stop codons. [NIH] Ophthalmic: Pertaining to the eye. [EU] Ophthalmic Artery: Artery originating from the internal carotid artery and distributing to the eye, orbit and adjacent facial structures. [NIH] Ophthalmologic: Pertaining to ophthalmology (= the branch of medicine dealing with the eye). [EU] Ophthalmologist: A medical doctor specializing in the diagnosis and medical or surgical treatment of visual disorders and eye disease. [NIH] Ophthalmology: A surgical specialty concerned with the structure and function of the eye and the medical and surgical treatment of its defects and diseases. [NIH] Ophthalmoscope: A lighted instrument used to examine the inside of the eye, including the retina and the optic nerve. [NIH] Ophthalmoscopy: Examination of the interior of the eye with an ophthalmoscope. [NIH] Opsin: A protein formed, together with retinene, by the chemical breakdown of metarhodopsin. [NIH] Optic Atrophy: Atrophy of the optic disk which may be congenital or acquired. This condition indicates a deficiency in the number of nerve fibers which arise in the retina and
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converge to form the optic disk, optic nerve, optic chiasm, and optic tracts. Glaucoma, ischemia, inflammation, a chronic elevation of intracranial pressure, toxins, optic nerve compression, and inherited conditions are relatively common causes of this condition. [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 disc: The circular area (disc) where the optic nerve connects to the retina. [NIH] Optic Disk: The portion of the optic nerve seen in the fundus with the ophthalmoscope. It is formed by the meeting of all the retinal ganglion cell axons as they enter the optic nerve. [NIH]
Optic Nerve: The 2nd cranial nerve. The optic nerve conveys visual information from the retina to the brain. The nerve carries the axons of the retinal ganglion cells which sort at the optic chiasm and continue via the optic tracts to the brain. The largest projection is to the lateral geniculate nuclei; other important targets include the superior colliculi and the suprachiasmatic nuclei. Though known as the second cranial nerve, it is considered part of the central nervous system. [NIH] Optic nerve head: The circular area (disc) where the optic nerve connects to the retina. [NIH] Optic Neuritis: Inflammation of the optic nerve. Commonly associated conditions include autoimmune disorders such as multiple sclerosis, infections, and granulomatous diseases. Clinical features include retro-orbital pain that is aggravated by eye movement, loss of color vision, and contrast sensitivity that may progress to severe visual loss, an afferent pupillary defect (Marcus-Gunn pupil), and in some instances optic disc hyperemia and swelling. Inflammation may occur in the portion of the nerve within the globe (neuropapillitis or anterior optic neuritis) or the portion behind the globe (retrobulbar neuritis or posterior optic neuritis). [NIH] Optometry: The professional practice of primary eye and vision care that includes the measurement of visual refractive power and the correction of visual defects with lenses or glasses. [NIH] Orbital: Pertaining to the orbit (= the bony cavity that contains the eyeball). [EU] Organ Culture: The growth in aseptic culture of plant organs such as roots or shoots, beginning with organ primordia or segments and maintaining the characteristics of the organ. [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] 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] Ovarian Follicle: Spheroidal cell aggregation in the ovary containing an ovum. It consists of an external fibro-vascular coat, an internal coat of nucleated cells, and a transparent, albuminous fluid in which the ovum is suspended. [NIH]
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Ovary: Either of the paired glands in the female that produce the female germ cells and secrete some of the female sex hormones. [NIH] Overexpress: An excess of a particular protein on the surface of a cell. [NIH] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]
Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). [NIH] 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] Oxygenation: The process of supplying, treating, or mixing with oxygen. No:1245 oxygenation the process of supplying, treating, or mixing with oxygen. [EU] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] 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] Parenteral: Not through the alimentary canal but rather by injection through some other route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intravenous, etc. [EU] Paresis: A general term referring to a mild to moderate degree of muscular weakness, occasionally used as a synonym for paralysis (severe or complete loss of motor function). In the older literature, paresis often referred specifically to paretic neurosyphilis. "General paresis" and "general paralysis" may still carry that connotation. Bilateral lower extremity paresis is referred to as paraparesis. [NIH] Paresthesias: Abnormal touch sensations, such as burning or prickling, that occur without an outside stimulus. [NIH] Parietal: 1. Of or pertaining to the walls of a cavity. 2. Pertaining to or located near the parietal bone, as the parietal lobe. [EU] Particle: A tiny mass of material. [EU] Parturition: The act or process of given birth to a child. [EU] Patch: A piece of material used to cover or protect a wound, an injured part, etc.: a patch
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over the eye. [NIH] Pathogen: Any disease-producing microorganism. [EU] Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Pathologies: The study of abnormality, especially the study of diseases. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]
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] Pentoxifylline: A methylxanthine derivative that inhibits phosphodiesterase and affects blood rheology. It improves blood flow by increasing erythrocyte and leukocyte flexibility. It also inhibits platelet aggregation. Pentoxifylline modulates immunologic activity by stimulating cytokine production. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Perception: The ability quickly and accurately to recognize similarities and differences among presented objects, whether these be pairs of words, pairs of number series, or multiple sets of these or other symbols such as geometric figures. [NIH] Percutaneous: Performed through the skin, as injection of radiopacque material in radiological examination, or the removal of tissue for biopsy accomplished by a needle. [EU] Perfusion: Bathing an organ or tissue with a fluid. In regional perfusion, a specific area of the body (usually an arm or a leg) receives high doses of anticancer drugs through a blood vessel. Such a procedure is performed to treat cancer that has not spread. [NIH] Pericytes: Smooth muscle cell that wraps around normal blood vessels. [NIH] Periodontal disease: Disease involving the supporting structures of the teeth (as the gums and periodontal membranes). [NIH] Periodontal disease: Disease involving the supporting structures of the teeth (as the gums and periodontal membranes). [NIH] Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] Peripheral Vascular Disease: Disease in the large blood vessels of the arms, legs, and feet. People who have had diabetes for a long time may get this because major blood vessels in their arms, legs, and feet are blocked and these limbs do not receive enough blood. The signs of PVD are aching pains in the arms, legs, and feet (especially when walking) and foot sores that heal slowly. Although people with diabetes cannot always avoid PVD, doctors say they have a better chance of avoiding it if they take good care of their feet, do not smoke, and keep both their blood pressure and diabetes under good control. [NIH]
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Peripheral vision: Side vision; ability to see objects and movement outside of the direct line of vision. [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] Perivascular: Situated around a vessel. [EU] Petechiae: Pinpoint, unraised, round red spots under the skin caused by bleeding. [NIH] Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] 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] Phorbol: Class of chemicals that promotes the development of tumors. [NIH] Phosphatidic Acids: Fatty acid derivatives of glycerophosphates. They are composed of glycerol bound in ester linkage with 1 mole of phosphoric acid at the terminal 3-hydroxyl group and with 2 moles of fatty acids at the other two hydroxyl groups. [NIH] Phosphodiesterase: Effector enzyme that regulates the levels of a second messenger, the cyclic GMP. [NIH] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Phosphorylated: Attached to a phosphate group. [NIH] Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. [NIH] Photocoagulation: Using a special strong beam of light (laser) to seal off bleeding blood vessels such as in the eye. The laser can also burn away blood vessels that should not have grown in the eye. This is the main treatment for diabetic retinopathy. [NIH] Photodynamic therapy: Treatment with drugs that become active when exposed to light. These drugs kill cancer cells. [NIH] Photoreceptor: Receptor capable of being activated by light stimuli, as a rod or cone cell of the eye. [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.
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[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] Pigmentation: Coloration or discoloration of a part by a pigment. [NIH] Pilot study: The initial study examining a new method or treatment. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [NIH] Placenta: A highly vascular fetal organ through which the fetus absorbs oxygen and other nutrients and excretes carbon dioxide and other wastes. It begins to form about the eighth day of gestation when the blastocyst adheres to the decidua. [NIH] Plana: The radiographic term applied to a vertebral body crushed to a thin plate. [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] Plasmin: A product of the lysis of plasminogen (profibrinolysin) by plasminogen activators. It is composed of two polypeptide chains, light (B) and heavy (A), with a molecular weight of 75,000. It is the major proteolytic enzyme involved in blood clot retraction or the lysis of fibrin and quickly inactivated by antiplasmins. EC 3.4.21.7. [NIH] Plasminogen Activator Inhibitor 1: A member of the serpin family of proteins. It inhibits both the tissue-type and urokinase-type plasminogen activators. [NIH] Plasminogen Activators: A heterogeneous group of proteolytic enzymes that convert plasminogen to plasmin. They are concentrated in the lysosomes of most cells and in the vascular endothelium, particularly in the vessels of the microcirculation. EC 3.4.21.-. [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.
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Also called thrombocytes. [NIH] Pleura: The thin serous membrane enveloping the lungs and lining the thoracic cavity. [NIH] Pleural: A circumscribed area of hyaline whorled fibrous tissue which appears on the surface of the parietal pleura, on the fibrous part of the diaphragm or on the pleura in the interlobar fissures. [NIH] Pleural cavity: A space enclosed by the pleura (thin tissue covering the lungs and lining the interior wall of the chest cavity). It is bound by thin membranes. [NIH] Pneumonia: Inflammation of the lungs. [NIH] Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Polyunsaturated fat: An unsaturated fat found in greatest amounts in foods derived from plants, including safflower, sunflower, corn, and soybean oils. [NIH] 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] Posterior chamber: The space between the back of the iris and the front face of the vitreous; filled with aqueous fluid. [NIH] 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] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] 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] Potentiates: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Preclinical: Before a disease becomes clinically recognizable. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU]
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Predisposition: A latent susceptibility to disease which may be activated under certain conditions, as by stress. [EU] Preeclampsia: A toxaemia of late pregnancy characterized by hypertension, edema, and proteinuria, when convulsions and coma are associated, it is called eclampsia. [EU] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Presynaptic: Situated proximal to a synapse, or occurring before the synapse is crossed. [EU] 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 exploring or sounding body cavities. [NIH] Prodrug: A substance that gives rise to a pharmacologically active metabolite, although not itself active (i. e. an inactive precursor). [NIH] Professional Practice: The use of one's knowledge in a particular profession. It includes, in the case of the field of biomedicine, professional activities related to health care and the actual performance of the duties related to the provision of health care. [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH] Proliferative Retinopathy: A disease of the small blood vessels of the retina of the eye. [NIH] Proline: A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Prone: Having the front portion of the body downwards. [NIH] Prophase: The first phase of cell division, in which the chromosomes become visible, the nucleus starts to lose its identity, the spindle appears, and the centrioles migrate toward opposite poles. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Proportional Hazards Models: Statistical models used in survival analysis that assert that the effect of the study factors on the hazard rate in the study population is multiplicative and does not change over time. [NIH] Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] Prostaglandin: Any of a group of components derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway that are extremely potent mediators of a diverse group of physiologic processes. The abbreviation for prostaglandin is PG; specific compounds are designated by adding one of the letters A through I to indicate the type of substituents found on the hydrocarbon skeleton and a subscript (1, 2 or 3) to indicate the number of double bonds in the hydrocarbon skeleton e.g., PGE2. The predominant naturally occurring prostaglandins all have two double bonds and are synthesized from arachidonic acid (5,8,11,14-eicosatetraenoic acid) by the pathway shown in
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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 D: Physiologically active prostaglandins found in many tissues and organs. They show pressor activity, are mediators of inflammation, and have potential antithrombotic effects. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein Isoforms: Different forms of a protein that may be produced from different genes, or from the same gene by alternative splicing. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Proteinuria: The presence of protein in the urine, indicating that the kidneys are not working properly. [NIH] Proteoglycans: Glycoproteins which have a very high polysaccharide content. [NIH] Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Psoriasis: A common genetically determined, chronic, inflammatory skin disease characterized by rounded erythematous, dry, scaling patches. The lesions have a predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region. Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in
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psoriasis. [NIH] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]
Pulmonary: Relating to the lungs. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] Pulmonary Edema: An accumulation of an excessive amount of watery fluid in the lungs, may be caused by acute exposure to dangerous concentrations of irritant gasses. [NIH] Pulmonary Embolism: Embolism in the pulmonary artery or one of its branches. [NIH] Pulmonary Fibrosis: Chronic inflammation and progressive fibrosis of the pulmonary alveolar walls, with steadily progressive dyspnea, resulting finally in death from oxygen lack or right heart failure. [NIH] Pulmonary hypertension: Abnormally high blood pressure in the arteries of the lungs. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]
Pupil: The aperture in the iris through which light passes. [NIH] Purines: A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include adenine and guanine, constituents of nucleic acids, as well as many alkaloids such as caffeine and theophylline. Uric acid is the metabolic end product of purine metabolism. [NIH] Purpura: Purplish or brownish red discoloration, easily visible through the epidermis, caused by hemorrhage into the tissues. [NIH] Pyrimidines: A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (cytosine, thymine, and uracil) and form the basic structure of the barbiturates. [NIH] Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] Quiescent: Marked by a state of inactivity or repose. [EU] 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
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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] Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH] Radiological: Pertaining to radiodiagnostic and radiotherapeutic procedures, and interventional radiology or other planning and guiding medical radiology. [NIH] Radiotherapy: The use of ionizing radiation to treat malignant neoplasms and other benign conditions. The most common forms of ionizing radiation used as therapy are x-rays, gamma rays, and electrons. A special form of radiotherapy, targeted radiotherapy, links a cytotoxic radionuclide to a molecule that targets the tumor. When this molecule is an antibody or other immunologic molecule, the technique is called radioimmunotherapy. [NIH] Random Allocation: A process involving chance used in therapeutic trials or other research endeavor for allocating experimental subjects, human or animal, between treatment and control groups, or among treatment groups. It may also apply to experiments on inanimate objects. [NIH] Randomization: Also called random allocation. Is allocation of individuals to groups, e.g., for experimental and control regimens, by chance. Within the limits of chance variation, random allocation should make the control and experimental groups similar at the start of an investigation and ensure that personal judgment and prejudices of the investigator do not influence allocation. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Randomized clinical trial: A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be in a randomized trial. [NIH] Reactive Oxygen Species: Reactive intermediate oxygen species including both radicals and non-radicals. These substances are constantly formed in the human body and have been shown to kill bacteria and inactivate proteins, and have been implicated in a number of diseases. Scientific data exist that link the reactive oxygen species produced by inflammatory phagocytes to cancer development. [NIH] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH]
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Refer: To send or direct for treatment, aid, information, de decision. [NIH] Reference Standards: A basis of value established for the measure of quantity, weight, extent or quality, e.g. weight standards, standard solutions, methods, techniques, and procedures used in diagnosis and therapy. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Refractive Errors: Deviations from the average or standard indices of refraction of the eye through its dioptric or refractive apparatus. [NIH] Refractive Power: The ability of an object, such as the eye, to bend light as light passes through it. [NIH] Regeneration: The natural renewal of a structure, as of a lost tissue or part. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Regression Analysis: Procedures for finding the mathematical function which best describes the relationship between a dependent variable and one or more independent variables. In linear regression (see linear models) the relationship is constrained to be a straight line and least-squares analysis is used to determine the best fit. In logistic regression (see logistic models) the dependent variable is qualitative rather than continuously variable and likelihood functions are used to find the best relationship. In multiple regression the dependent variable is considered to depend on more than a single independent variable. [NIH]
Rehabilitative: Instruction of incapacitated individuals or of those affected with some mental disorder, so that some or all of their lost ability may be regained. [NIH] Reliability: Used technically, in a statistical sense, of consistency of a test with itself, i. e. the extent to which we can assume that it will yield the same result if repeated a second time. [NIH]
Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Renal failure: Progressive renal insufficiency and uremia, due to irreversible and progressive renal glomerular tubular or interstitial disease. [NIH] Renin: An enzyme which is secreted by the kidney and is formed from prorenin in plasma and kidney. The enzyme cleaves the Leu-Leu bond in angiotensinogen to generate angiotensin I. EC 3.4.23.15. (Formerly EC 3.4.99.19). [NIH] Renin-Angiotensin System: A system consisting of renin, angiotensin-converting enzyme, and angiotensin II. Renin, an enzyme produced in the kidney, acts on angiotensinogen, an alpha-2 globulin produced by the liver, forming angiotensin I. The converting enzyme contained in the lung acts on angiotensin I in the plasma converting it to angiotensin II, the most powerful directly pressor substance known. It causes contraction of the arteriolar smooth muscle and has other indirect actions mediated through the adrenal cortex. [NIH] 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] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic
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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] Retinae: A congenital notch or cleft of the retina, usually located inferiorly. [NIH] Retinal: 1. Pertaining to the retina. 2. The aldehyde of retinol, derived by the oxidative enzymatic splitting of absorbed dietary carotene, and having vitamin A activity. In the retina, retinal combines with opsins to form visual pigments. One isomer, 11-cis retinal combines with opsin in the rods (scotopsin) to form rhodopsin, or visual purple. Another, all-trans retinal (trans-r.); visual yellow; xanthopsin) results from the bleaching of rhodopsin by light, in which the 11-cis form is converted to the all-trans form. Retinal also combines with opsins in the cones (photopsins) to form the three pigments responsible for colour vision. Called also retinal, and retinene1. [EU] Retinal Artery: Central retinal artery and its branches. It arises from the ophthalmic artery, pierces the optic nerve and runs through its center, enters the eye through the porus opticus and branches to supply the retina. [NIH] Retinal Detachment: Separation of the inner layers of the retina (neural retina) from the pigment epithelium. Retinal detachment occurs more commonly in men than in women, in eyes with degenerative myopia, in aging and in aphakia. It may occur after an uncomplicated cataract extraction, but it is seen more often if vitreous humor has been lost during surgery. (Dorland, 27th ed; Newell, Ophthalmology: Principles and Concepts, 7th ed, p310-12). [NIH] Retinal Ganglion Cells: Cells of the innermost nuclear layer of the retina, the ganglion cell layer, which project axons through the optic nerve to the brain. They are quite variable in size and in the shapes of their dendritic arbors, which are generally confined to the inner plexiform layer. [NIH] Retinal Hemorrhage: Bleeding from the vessels of the retina. [NIH] Retinal Neovascularization: Formation of new blood vessels originating from the retinal veins and extending along the inner (vitreal) surface of the retina. [NIH] Retinal pigment epithelium: The pigment cell layer that nourishes the retinal cells; located just outside the retina and attached to the choroid. [NIH] Retinal Vein: Central retinal vein and its tributaries. It runs a short course within the optic nerve and then leaves and empties into the superior ophthalmic vein or cavernous sinus. [NIH]
Retinal Vein Occlusion: Occlusion of the retinal vein. Those at high risk for this condition include patients with hypertension, diabetes mellitus, arteriosclerosis, and other cardiovascular diseases. [NIH] Retinal Vessels: The vessels which supply and drain the retina. [NIH] 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 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] 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]
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Retrobulbar: Behind the pons. [EU] Retroviral vector: RNA from a virus that is used to insert genetic material into cells. [NIH] Rheology: The study of the deformation and flow of matter, usually liquids or fluids, and of the plastic flow of solids. The concept covers consistency, dilatancy, liquefaction, resistance to flow, shearing, thixotrophy, and viscosity. [NIH] 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] Rhodopsin: A photoreceptor protein found in retinal rods. It is a complex formed by the binding of retinal, the oxidized form of retinol, to the protein opsin and undergoes a series of complex reactions in response to visible light resulting in the transmission of nerve impulses to the brain. [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] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Ristocetin: An antibiotic mixture of two components, A and B, obtained from Nocardia lurida (or the same substance produced by any other means). It is no longer used clinically because of its toxicity. It causes platelet agglutination and blood coagulation and is used to assay those functions in vitro. [NIH] Rod: A reception for vision, located in the retina. [NIH] Scans: Pictures of structures inside the body. Scans often used in diagnosing, staging, and monitoring disease include liver scans, bone scans, and computed tomography (CT) or computerized axial tomography (CAT) scans and magnetic resonance imaging (MRI) scans. In liver scanning and bone scanning, radioactive substances that are injected into the bloodstream collect in these organs. A scanner that detects the radiation is used to create pictures. In CT scanning, an x-ray machine linked to a computer is used to produce detailed pictures of organs inside the body. MRI scans use a large magnet connected to a computer to create pictures of areas inside the body. [NIH] Sclera: The tough white outer coat of the eyeball, covering approximately the posterior fivesixths of its surface, and continuous anteriorly with the cornea and posteriorly with the external sheath of the optic nerve. [EU] 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] 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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Segmental: Describing or pertaining to a structure which is repeated in similar form in successive segments of an organism, or which is undergoing segmentation. [NIH] Segregation: The separation in meiotic cell division of homologous chromosome pairs and their contained allelomorphic gene pairs. [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] 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] Sequence Homology: The degree of similarity between sequences. Studies of amino acid and nucleotide sequences provide useful information about the genetic relatedness of certain species. [NIH] Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from glycine or threonine. It is involved in the biosynthesis of purines, pyrimidines, and other amino acids. [NIH] Serine Endopeptidases: Any member of the group of endopeptidases containing at the active site a serine residue involved in catalysis. EC 3.4.21. [NIH] Serine Proteinase Inhibitors: Exogenous or endogenous compounds which inhibit serine endopeptidases. [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] Sharpness: The apparent blurring of the border between two adjacent areas of a radiograph having different optical densities. [NIH] Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled
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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] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]
Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] 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] Soma: The body as distinct from the mind; all the body tissue except the germ cells; all the axial body. [NIH] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Somatic cells: All the body cells except the reproductive (germ) cells. [NIH] Somatic mutations: Alterations in DNA that occur after conception. Somatic mutations can occur in any of the cells of the body except the germ cells (sperm and egg) and therefore are not passed on to children. These alterations can (but do not always) cause cancer or other diseases. [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] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectroscopic: The recognition of elements through their emission spectra. [NIH] Sperm: The fecundating fluid of the male. [NIH] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in
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the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Stabilization: The creation of a stable state. [EU] Staging: Performing exams and tests to learn the extent of the cancer within the body, especially whether the disease has spread from the original site to other parts of the body. [NIH]
Statistically significant: Describes a mathematical measure of difference between groups. The difference is said to be statistically significant if it is greater than what might be expected to happen by chance alone. [NIH] Stem Cells: Relatively undifferentiated cells of the same lineage (family type) that retain the ability to divide and cycle throughout postnatal life to provide cells that can become specialized and take the place of those that die or are lost. [NIH] Stereoscopic: Accurate depth perception in the presence of binocular single vision, due to the slight disparity in the two retinal images of the same object. [NIH] Steroids: Drugs used to relieve swelling and inflammation. [NIH] Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stool: The waste matter discharged in a bowel movement; feces. [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] Stroma: The middle, thickest layer of tissue in the cornea. [NIH] Stromal: Large, veil-like cell in the bone marrow. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subconjunctival: Situated or occurring beneath the conjunctiva. [EU] Subcutaneous: Beneath the skin. [NIH] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]
Substrate: A substance upon which an enzyme acts. [EU] Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts. [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
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(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] 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] Synapse: The region where the processes of two neurons come into close contiguity, and the nervous impulse passes from one to the other; the fibers of the two are intermeshed, but, according to the general view, there is no direct contiguity. [NIH] 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] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Systemic: Affecting the entire body. [NIH] Systemic disease: Disease that affects the whole body. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Systolic blood pressure: The maximum pressure in the artery produced as the heart contracts and blood begins to flow. [NIH] Telangiectasia: The permanent enlargement of blood vessels, causing redness in the skin or mucous membranes. [NIH] Telecommunications: Transmission of information over distances via electronic means. [NIH]
Telemedicine: Delivery of health services via remote telecommunications. This includes interactive consultative and diagnostic services. [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] Tendon: A discrete band of connective tissue mainly composed of parallel bundles of collagenous fibers by which muscles are attached, or two muscles bellies joined. [NIH] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH]
Dictionary 235
Thrombocytes: Blood cells that help prevent bleeding by causing blood clots to form. Also called platelets. [NIH] Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thromboxanes: Physiologically active compounds found in many organs of the body. They are formed in vivo from the prostaglandin endoperoxides and cause platelet aggregation, contraction of arteries, and other biological effects. Thromboxanes are important mediators of the actions of polyunsaturated fatty acids transformed by cyclooxygenase. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU] Tomography: Imaging methods that result in sharp images of objects located on a chosen plane and blurred images located above or below the plane. [NIH] Tonometry: The standard to determine the fluid pressure inside the eye (intraocular pressure). [NIH] Tooth Preparation: Procedures carried out with regard to the teeth or tooth structures preparatory to specified dental therapeutic and surgical measures. [NIH] Topical: On the surface of the body. [NIH] Torsion: A twisting or rotation of a bodily part or member on its axis. [NIH] Toxaemia: 1. The condition resulting from the spread of bacterial products (toxins) by the bloodstream. 2. A condition resulting from metabolic disturbances, e.g. toxaemia of pregnancy. [EU] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxin: A poison; frequently used to refer specifically to a protein produced by some higher plants, certain animals, and pathogenic bacteria, which is highly toxic for other living organisms. Such substances are differentiated from the simple chemical poisons and the vegetable alkaloids by their high molecular weight and antigenicity. [EU] Trace element: Substance or element essential to plant or animal life, but present in extremely small amounts. [NIH] Traction: The act of pulling. [NIH] Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. [NIH] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle
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(pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transgenes: Genes that are introduced into an organism using gene transfer techniques. [NIH]
Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] 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] Triad: Trivalent. [NIH] Triamcinolone Acetonide: An esterified form of triamcinolone. It is an anti-inflammatory glucocorticoid used topically in the treatment of various skin disorders. Intralesional, intramuscular, and intra-articular injections are also administered under certain conditions. [NIH]
Tricuspid Atresia: Absence of the orifice between the right atrium and ventricle, with the presence of an atrial defect through which all the systemic venous return reaches the left heart. As a result, there is left ventricular hypertrophy because the right ventricle is absent or not functional. [NIH] 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] Trophic: Of or pertaining to nutrition. [EU] Trypsin: A serine endopeptidase that is formed from trypsinogen in the pancreas. It is converted into its active form by enteropeptidase in the small intestine. It catalyzes hydrolysis of the carboxyl group of either arginine or lysine. EC 3.4.21.4. [NIH] Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Tumor model: A type of animal model which can be 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] Tumour: 1. Swelling, one of the cardinal signs of inflammations; morbid enlargement. 2. A new growth of tissue in which the multiplication of cells is uncontrolled and progressive; called also neoplasm. [EU] Type 2 diabetes: Usually characterized by a gradual onset with minimal or no symptoms of metabolic disturbance and no requirement for exogenous insulin. The peak age of onset is 50 to 60 years. Obesity and possibly a genetic factor are usually present. [NIH] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Urban Health: The status of health in urban populations. [NIH]
Dictionary 237
Urban Population: The inhabitants of a city or town, including metropolitan areas and suburban areas. [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] 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] 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] Urokinase: A drug that dissolves blood clots or prevents them from forming. [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] Uvea: The middle coat of the eyeball, consisting of the choroid in the back of the eye and the ciliary body and iris in the front of the eye. [NIH] Uveitis: An inflammation of part or all of the uvea, the middle (vascular) tunic of the eye, and commonly involving the other tunics (the sclera and cornea, and the retina). [EU] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Vancomycin: Antibacterial obtained from Streptomyces orientalis. It is a glycopeptide related to ristocetin that inhibits bacterial cell wall assembly and is toxic to kidneys and the inner ear. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vascular endothelial growth factor: VEGF. A substance made by cells that stimulates new blood vessel formation. [NIH] Vascular Resistance: An expression of the resistance offered by the systemic arterioles, and to a lesser extent by the capillaries, to the flow of blood. [NIH] Vasoactive: Exerting an effect upon the calibre of blood vessels. [EU] Vasodilator: An agent that widens blood vessels. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venous: Of or pertaining to the veins. [EU] Venous Thrombosis: The formation or presence of a thrombus within a vein. [NIH] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Ventricular: Pertaining to a ventricle. [EU] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH]
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Vertebral: Of or pertaining to a vertebra. [EU] Vertigo: An illusion of movement; a sensation as if the external world were revolving around the patient (objective vertigo) or as if he himself were revolving in space (subjective vertigo). The term is sometimes erroneously used to mean any form of dizziness. [EU] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Viral vector: A type of virus used in cancer therapy. The virus is changed in the laboratory and cannot cause disease. Viral vectors produce tumor antigens (proteins found on a tumor cell) and can stimulate an antitumor immune response in the body. Viral vectors may also be used to carry genes that can change cancer cells back to normal cells. [NIH] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Viscera: Any of the large interior organs in any one of the three great cavities of the body, especially in the abdomen. [NIH] Visual Acuity: Acuteness or clearness of vision, especially of form vision, which is dependent mainly on the sharpness of the retinal focus. [NIH] Visual Cortex: Area of the occipital lobe concerned with vision. [NIH] Visual field: The entire area that can be seen when the eye is forward, including peripheral vision. [NIH] Vitelline Membrane: The plasma membrane of the egg. [NIH] Vitrectomy: Removal of the whole or part of the vitreous body in treating endophthalmitis, diabetic retinopathy, retinal detachment, intraocular foreign bodies, and some types of glaucoma. [NIH] Vitreoretinal: A rare familial condition characterized by a clear vitreous, except for preretinal filaments and veils which have been loosened from the retina, a dense hyaloid membrane which is perforated and detached, and masses of peripheral retinal pigmentation inters. [NIH] Vitreoretinopathy, Proliferative: Vitreoretinal membrane shrinkage or contraction secondary to the proliferation of primarily retinal pigment epithelial cells and glial cells, particularly fibrous astrocytes, followed by membrane formation. The formation of fibrillar collagen and cellular proliferation appear to be the basis for the contractile properties of the epiretinal and vitreous membranes. [NIH] Vitreous: Glasslike or hyaline; often used alone to designate the vitreous body of the eye (corpus vitreum). [EU] Vitreous Body: The transparent, semigelatinous substance that fills the cavity behind the crystalline lens of the eye and in front of the retina. It is contained in a thin hyoid membrane and forms about four fifths of the optic globe. [NIH] Vitreous Humor: The transparent, colorless mass of gel that lies behind the lens and in front of the retina and fills the center of the eyeball. [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
Dictionary 239
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]
War: Hostile conflict between organized groups of people. [NIH] Warfarin: An anticoagulant that acts by inhibiting the synthesis of vitamin K-dependent coagulation factors. Warfarin is indicated for the prophylaxis and/or treatment of venous thrombosis and its extension, pulmonary embolism, and atrial fibrillation with embolization. It is also used as an adjunct in the prophylaxis of systemic embolism after myocardial infarction. Warfarin is also used as a rodenticide. [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]
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] Yolk Sac: An embryonic membrane formed from endoderm and mesoderm. In reptiles and birds it incorporates the yolk into the digestive tract for nourishing the embryo. In placental mammals its nutritional function is vestigial; however, it is the source of most of the intestinal mucosa and the site of formation of the germ cells. It is sometimes called the vitelline sac, which should not be confused with the vitelline membrane of the egg. [NIH]
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INDEX 3 3-dimensional, 60, 175 A Abdomen, 175, 196, 210, 221, 233, 238 Abdominal, 175, 176, 192, 219, 221 Aberrant, 43, 49, 52, 175 Ablate, 30, 175 Ablation, 105, 175 Acatalasia, 175, 185 Accommodation, 9, 175, 215 Acetylcholine, 175, 216 Acidosis, 39, 175 Actin, 24, 175 Activities of Daily Living, 27, 175 Acuity, 12, 34, 69, 175 Acyl, 29, 175, 211 Adaptability, 175, 185 Adaptation, 64, 71, 175, 191, 216 Adenovirus, 27, 29, 36, 175 Adipocytes, 176, 189, 209 Adjustment, 175, 176, 191 Adolescence, 99, 176 Adrenal Cortex, 176, 190, 191, 228 Adrenergic, 176, 193, 196, 234 Adverse Effect, 176, 177, 231 Afferent, 176, 209, 218 Affinity, 14, 50, 176, 181, 210 Agar, 176, 222 Age of Onset, 176, 236 Aggravation, 72, 137, 176 Agonist, 19, 48, 176, 193 Albumin, 12, 16, 54, 151, 176, 222 Aldose Reductase Inhibitor, 14, 128, 129, 176 Algorithms, 57, 177, 182 Alimentary, 177, 207, 219 Alkaline, 29, 175, 177, 183 Alleles, 25, 177, 203 Allograft, 138, 177 Alpha Particles, 177, 226 Alternative medicine, 150, 177 Alternative Splicing, 131, 140, 177, 225 Amaurosis, 81, 177 Amaurosis Fugax, 81, 177 Amblyopia, 78, 177 Ameliorating, 139, 177 Amino Acid Sequence, 177, 179, 197
Amino Acids, 131, 177, 178, 217, 220, 223, 225, 230, 231, 236 Anaesthesia, 178, 205 Analogous, 178, 194, 236 Anaphylatoxins, 178, 188 Anatomical, 163, 178, 181, 205, 213, 230 Androgens, 176, 178, 190 Anemia, 4, 178, 202 Anesthesia, 39, 178 Angiogenesis Factor, 140, 178 Angiogenesis inhibitor, 37, 60, 178, 196 Angiography, 87, 178 Angiopathy, 137, 178 Angiotensinogen, 23, 178, 228 Animal model, 31, 32, 35, 38, 41, 59, 65, 66, 68, 149, 150, 178, 236 Anions, 176, 178, 208 Anomalies, 39, 179 Anterior chamber, 138, 179, 208 Anterior Eye Segment, 44, 179 Antiallergic, 179, 190 Antiangiogenesis, 133, 179 Antiangiogenic, 39, 49, 65, 179 Antibiotic, 179, 191, 193, 230 Antibodies, 33, 37, 130, 139, 179, 181, 201, 203, 204, 222 Antibody, 16, 131, 141, 176, 179, 188, 201, 203, 205, 208, 212, 214, 227, 232, 239 Anticoagulant, 133, 179, 225, 239 Antigen, 32, 40, 176, 179, 188, 203, 204, 205, 206, 212, 213 Antigen-Antibody Complex, 179, 188 Anti-inflammatory, 43, 134, 179, 181, 190, 192, 200, 236 Anti-Inflammatory Agents, 179, 181, 190 Antimetabolite, 179, 213 Antineoplastic, 179, 190, 193, 199, 213 Antioxidant, 119, 179, 181, 219 Antithrombotic, 54, 179, 225 Anuria, 179, 208 Anus, 179, 207 Aorta, 45, 179, 237 Aphakia, 179, 229 Apolipoproteins, 180, 210 Aponeurosis, 180, 199 Apoptosis, 29, 32, 38, 40, 43, 51, 86, 133, 135, 138, 180, 184 Applicability, 42, 180
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Approximate, 15, 180 Aqueous, 72, 99, 106, 180, 182, 183, 187, 191, 204, 209, 223 Aqueous fluid, 180, 223 Aqueous humor, 99, 180, 183, 187 Arachidonic Acid, 21, 43, 180, 194, 209, 224 Arginine, 46, 178, 180, 216, 236 Argon, 76, 97, 136, 180 Arterial, 30, 38, 132, 133, 137, 180, 186, 190, 204, 225, 234 Arteries, 23, 41, 57, 178, 179, 180, 183, 190, 211, 215, 226, 235 Arteriolar, 21, 57, 180, 183, 228 Arterioles, 180, 183, 184, 213, 237 Arteriolosclerosis, 180 Arteriosclerosis, 25, 180, 204, 229 Arteriovenous, 57, 180, 213 Artery, 37, 53, 180, 181, 190, 192, 195, 217, 226, 229, 234 Articular, 181, 210, 236 Ascites, 141, 181, 217 Ascorbic Acid, 121, 181, 204 Aseptic, 181, 218 Aspartate, 19, 181 Aspirin, 7, 34, 54, 73, 181 Assay, 60, 181, 230 Astigmatism, 181, 228 Astrocytes, 26, 181, 203, 213, 238 Atrial, 181, 190, 236, 239 Atrial Fibrillation, 181, 239 Atrioventricular, 181, 190 Atrium, 181, 190, 236, 237 Attenuation, 68, 181 Autoantibodies, 77, 181 Autoantigens, 181 Autologous, 46, 181 Axons, 181, 218, 229 B Bacteria, 175, 179, 181, 182, 195, 198, 203, 211, 213, 227, 235, 237 Bacterial Physiology, 175, 181 Bacterium, 181, 188 Basal Ganglia, 182, 199 Base, 16, 24, 29, 182, 208, 234 Basement Membrane, 20, 36, 66, 67, 93, 140, 182, 197, 209 Benign, 55, 180, 182, 199, 201, 215, 227 Benzoic Acid, 152, 182 Bilateral, 61, 182, 219, 229 Bilirubin, 176, 182 Bioavailability, 37, 182
Biochemical, 23, 35, 50, 57, 75, 177, 179, 182, 208, 231 Bioengineering, 46, 156, 182 Biological therapy, 182, 201 Biological Transport, 182, 192 Biopsy, 54, 182, 220 Biosynthesis, 180, 182, 231 Biotechnology, 70, 150, 157, 182 Bladder, 182, 188, 199, 205, 214, 237 Blastocyst, 182, 189, 222 Blood Cell Count, 182, 202 Blood Coagulation, 133, 183, 184, 230 Blood Coagulation Factors, 183 Blood Glucose, 3, 4, 10, 12, 35, 49, 116, 137, 152, 162, 163, 164, 183, 202, 204, 206 Blood pressure, 11, 12, 23, 54, 58, 76, 97, 151, 164, 173, 183, 184, 204, 214, 220, 226 Blood vessel, 15, 25, 27, 29, 30, 37, 39, 40, 45, 52, 58, 60, 130, 131, 137, 138, 139, 140, 162, 164, 178, 179, 183, 184, 186, 187, 190, 195, 196, 200, 201, 208, 209, 210, 211, 213, 220, 221, 224, 229, 232, 233, 234, 235, 237 Blood-Aqueous Barrier, 76, 183 Blood-Retinal Barrier, 43, 110, 183 Blot, 36, 66, 183 Bone Marrow, 183, 191, 200, 211, 232, 233 Bone scan, 183, 230 Brachytherapy, 183, 207, 208, 227, 239 Bradykinin, 183, 216, 222 C Cadaver, 24, 183 Calcification, 137, 180, 183 Calcium, 19, 183, 188, 212, 213, 231 Callus, 184, 195 Capillary, 20, 23, 37, 47, 66, 120, 138, 164, 183, 184, 200, 237 Capillary Resistance, 120, 184 Capsules, 184, 200 Carbogen, 56, 184 Carbohydrate, 47, 184, 190, 200, 201, 223 Carbon Dioxide, 184, 222, 228 Carcinogenic, 184, 206, 217, 224 Carcinogens, 184, 186, 217 Carcinoma, 141, 184 Cardiac, 64, 181, 184, 190, 196, 197, 215 Cardiomyopathy, 129, 184 Cardiovascular, 7, 8, 21, 41, 48, 64, 92, 130, 152, 184, 209, 210, 229, 231 Cardiovascular disease, 7, 8, 21, 48, 92, 130, 184, 210, 229 Cardiovascular System, 64, 184
243
Carotene, 184, 229 Case report, 4, 184, 187 Caspase, 38, 184 Catalase, 33, 175, 185 Cataract, 13, 22, 48, 61, 72, 77, 100, 102, 179, 185, 229 Catecholamine, 185, 193 Cathode, 185, 195 Cations, 29, 185, 208 Caudal, 185, 223 Causal, 185, 202, 207 Cavernous Sinus, 185, 229 Cell Adhesion, 133, 185, 206 Cell Communication, 15, 185 Cell Cycle, 138, 185 Cell Death, 19, 32, 38, 41, 180, 185, 215 Cell Differentiation, 45, 185, 231 Cell Division, 181, 185, 201, 212, 214, 222, 224, 231 Cell Extracts, 33, 185 Cell membrane, 133, 182, 185, 192, 197, 221, 239 Cell motility, 185, 203 Cell proliferation, 14, 29, 39, 59, 62, 133, 137, 138, 180, 185, 231 Cell Survival, 37, 185, 201 Cellular adhesion, 20, 186 Central Nervous System, 175, 186, 199, 201, 202, 209, 213, 214, 218, 231 Centrifugation, 186, 202 Cerebral, 57, 182, 186, 189, 196, 197 Cerebral Cortex, 186, 197 Cerebrovascular, 184, 186 Cerebrum, 186 Chemotactic Factors, 186, 188 Chemotaxis, 46, 186 Chemotherapy, 186, 209 Cholesterol, 21, 58, 97, 135, 186, 190, 194, 204, 210, 211, 212 Cholesterol Esters, 186, 210 Chondrocytes, 186, 198 Chorioretinitis, 186, 229 Choroid, 13, 32, 63, 186, 229, 237 Choroidal Neovascularization, 32, 35, 63, 186 Chromatin, 180, 186, 211 Chromium, 120, 186 Chromosome, 186, 210, 231 Chronic, 13, 20, 29, 30, 62, 140, 144, 152, 186, 187, 193, 196, 205, 208, 218, 225, 226, 233 Chronic Disease, 152, 186
Chylomicrons, 186, 210 Ciliary, 180, 183, 187, 237 Ciliary Body, 183, 187, 237 Ciliary processes, 180, 187 Circulatory system, 140, 187 Cirrhosis, 187, 202 CIS, 53, 187, 229 Clinical Medicine, 187, 223 Clinical study, 187, 189 Clinical trial, 5, 6, 12, 13, 14, 16, 18, 19, 42, 43, 62, 132, 157, 187, 189, 191, 193, 220, 225, 227 Cloning, 140, 182, 187 Clot Retraction, 187, 222 Coagulation, 183, 187, 203, 209, 222, 239 Codons, 187, 217 Coenzyme, 181, 187 Cofactor, 46, 187, 225 Cohort Studies, 18, 42, 187 Collagen, 59, 61, 66, 68, 80, 133, 137, 182, 188, 198, 212, 222, 224, 238 Colloidal, 176, 188 Competency, 31, 188 Complement, 46, 59, 82, 178, 188, 200, 206, 222 Complement Activation, 82, 178, 188 Complementary and alternative medicine, 119, 123, 188 Complementary medicine, 119, 188 Compliance, 54, 74, 188 Computational Biology, 157, 188 Computed tomography, 189, 230 Computerized axial tomography, 189, 230 Conception, 189, 198, 232 Cones, 189, 229 Conjugated, 182, 189, 191 Conjunctiva, 68, 189, 233 Connective Tissue, 35, 61, 181, 183, 188, 189, 190, 198, 213, 234 Connective Tissue Cells, 189 Constitutional, 189, 229 Constriction, 189, 208 Contraindications, ii, 189 Contrast medium, 178, 189 Contrast Sensitivity, 69, 94, 189, 218 Control group, 7, 31, 54, 189, 227 Controlled clinical trial, 48, 189 Controlled study, 54, 189 Convulsions, 189, 194, 224 Cor, 36, 190 Cornea, 28, 36, 67, 128, 138, 179, 180, 181, 190, 208, 230, 233, 237
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Diabetic Retinopathy
Corneal Stroma, 36, 190 Coronary, 37, 52, 53, 184, 190, 215 Coronary heart disease, 52, 184, 190 Coronary Thrombosis, 190, 215 Corpus, 140, 190, 238 Corpus Luteum, 140, 190 Corpuscle, 190, 197 Cortex, 177, 190 Cortical, 24, 61, 64, 177, 190, 197 Corticosteroid, 138, 190 Cortisol, 176, 191 Cortisone, 191, 192 Cranial, 191, 201, 215, 218, 220 Creatinine, 12, 100, 191, 208 Criterion, 10, 14, 191 Crossing-over, 191, 227 Curative, 136, 191, 234 Cyclic, 185, 191, 201, 216, 221, 225 Cyclosporine, 138, 191 Cytochrome, 38, 191 Cytokine, 191, 207, 220 Cytoplasm, 180, 185, 191, 196, 201, 211, 230 Cytoskeleton, 133, 191, 206 Cytostatic, 138, 191 Cytotoxic, 131, 191, 227, 232 D Dark Adaptation, 69, 191 Daunorubicin, 191, 193 Decidua, 191, 222 Defense Mechanisms, 191, 206 Degenerative, 192, 211, 229 Deletion, 15, 95, 180, 192 Delivery of Health Care, 192, 202 Dendrites, 15, 192, 215 Dendritic, 16, 192, 212, 229 Depolarization, 192, 232 Deprivation, 177, 192 Depth Perception, 192, 233 Deuterium, 192, 203 Developed Countries, 136, 192 Dexamethasone, 68, 192 Diagnostic procedure, 127, 151, 192 Diagnostic Services, 192, 234 Diaphragm, 192, 223 Diastole, 192 Diastolic, 5, 12, 192, 204 Diastolic blood pressure, 5, 12, 192 Diffusion, 38, 68, 182, 192, 205 Digestion, 177, 192, 210, 233 Digestive tract, 192, 232, 239 Digital photography, 78, 192
Dihydrotestosterone, 193, 227 Dilation, 163, 183, 193 Direct, iii, 10, 26, 36, 63, 136, 185, 187, 193, 211, 221, 228, 234 Discrete, 66, 193, 210, 234 Discrimination, 5, 193 Disease Progression, 43, 58, 193 Disparity, 193, 233 Dissociation, 176, 193 Distal, 47, 193, 225 Diuretic, 193, 232 Dominance, 59, 193 Dopamine, 21, 193, 216, 221 Dorsal, 193, 223 Dorsum, 193, 199 Double-blind, 54, 193 Doxorubicin, 131, 193 Drive, ii, vi, 6, 10, 11, 15, 108, 115, 144, 193 Drug Delivery Systems, 68, 194 Drug Design, 14, 60, 194 Drug Interactions, 194 Drug Tolerance, 194, 235 Duodenum, 194, 233 Dyslipidemia, 20, 194 Dyspnea, 194, 226 Dystrophy, 35, 194 E Eclampsia, 194, 224 Edema, 6, 11, 13, 18, 36, 62, 63, 66, 72, 80, 87, 97, 109, 120, 143, 194, 217, 224 Effector, 43, 175, 188, 194, 221 Efficacy, 11, 13, 24, 31, 48, 49, 65, 73, 83, 194 Eicosanoids, 43, 194 Elasticity, 48, 180, 194 Elastin, 188, 194, 198 Electrolysis, 178, 185, 194 Electrolyte, 190, 194, 208, 214, 223 Electrons, 179, 182, 185, 195, 208, 211, 219, 226, 227 Electroretinogram, 38, 63, 101, 195 Elementary Particles, 195, 211, 216, 225 Emboli, 195, 239 Embolism, 195, 226, 239 Embolization, 195, 239 Embolus, 195, 205 Embryo, 25, 182, 185, 195, 205, 213, 239 Embryogenesis, 58, 195 Empirical, 42, 195 Enalapril, 54, 195 Endoderm, 195, 239
245
Endogenous, 19, 29, 46, 49, 52, 65, 181, 183, 193, 194, 195, 196, 231, 235 Endometrium, 140, 191, 195 Endonucleases, 33, 195 Endophthalmitis, 195, 238 Endorphins, 195, 216 Endostatin, 36, 106, 196 Endothelium, 25, 37, 51, 196, 216, 222 Endothelium, Lymphatic, 196 Endothelium, Vascular, 196 Endothelium-derived, 196, 216 Endotoxins, 188, 196, 208 End-stage renal, 151, 196 Energy balance, 196, 209 Enkephalins, 196, 216 Enteropeptidase, 196, 236 Environmental Health, 156, 158, 196 Enzymatic, 21, 184, 188, 196, 212, 229 Epidemic, 9, 196 Epidemiological, 3, 8, 11, 42, 49, 59, 69, 151, 196 Epigastric, 196, 219 Epinephrine, 176, 193, 196, 216, 236 Epiretinal Membrane, 21, 24, 82, 101, 197 Epithelial, 32, 36, 86, 93, 182, 187, 191, 197, 203, 209, 238 Epithelial Cells, 32, 86, 197, 203, 209, 238 Epithelium, 36, 49, 65, 99, 110, 182, 183, 196, 197, 208, 229 Erectile, 48, 152, 197 Erection, 197 Erythrocyte Membrane, 72, 86, 197 Erythrocytes, 178, 182, 183, 197, 202 Esophagus, 192, 197, 233 Estrogen, 85, 197 Eukaryotic Cells, 197, 205 Evoke, 26, 197, 233 Excitability, 15, 197 Excitation, 197, 216 Excitatory, 26, 41, 197, 201 Excrete, 179, 197, 208 Exocrine, 197, 219 Exogenous, 29, 85, 195, 197, 231, 236 Exon, 177, 197 Expiration, 197, 228 Expiratory, 8, 197 Extensor, 197, 225 External-beam radiation, 197, 208, 226, 239 Extracellular, 15, 19, 26, 35, 37, 41, 131, 133, 137, 181, 189, 197, 198, 206, 212
Extracellular Matrix, 15, 35, 37, 131, 133, 189, 197, 198, 206, 212 Extracellular Matrix Proteins, 198, 212 Extracellular Space, 197, 198 Extraction, 57, 179, 198, 229 Extrapyramidal, 193, 198 Eye Infections, 175, 198 F Family Planning, 157, 198 Fat, 89, 176, 178, 180, 183, 184, 190, 195, 198, 209, 210, 214, 217, 223, 232, 236 Fatty acids, 20, 120, 176, 194, 198, 201, 221, 224 Fetus, 140, 198, 222, 224, 237 Fibrin, 54, 183, 187, 198, 222, 234 Fibrinogen, 198, 222, 234 Fibroblast Growth Factor, 130, 198 Fibroblasts, 189, 198, 207 Fibronectin, 66, 103, 131, 133, 137, 198 Fibrosis, 137, 198, 226, 230 Fluorescein Angiography, 65, 111, 144, 163, 198 Fold, 23, 25, 198, 219 Forearm, 183, 198 Fovea, 45, 198 Free Radicals, 21, 179, 193, 199 Functional magnetic resonance imaging, 56, 199 Fundus, 5, 18, 19, 26, 28, 30, 35, 45, 53, 57, 58, 71, 73, 83, 102, 108, 109, 199, 218 Fungistatic, 182, 199 G Galactitol, 129, 199 Galactokinase, 199 Galactosemia, 199 Gallbladder, 175, 199 Gamma-interferon, 199, 206 Ganglion, 15, 19, 199, 218, 229 Gas, 180, 184, 192, 199, 203, 216 Gastric, 129, 199 Gastrin, 199, 203 Gastrointestinal, 4, 134, 141, 183, 196, 199, 209, 231, 233 Gene Expression, 20, 25, 32, 106, 199 Gene Expression Profiling, 25, 199 Gene Therapy, 24, 35, 38, 51, 175, 199 Genetic Engineering, 182, 187, 200 Genetics, 25, 72, 75, 94, 100, 114, 129, 193, 200 Genotype, 26, 91, 200, 221 Germ Cells, 200, 212, 219, 232, 239 Gestation, 200, 222
246
Diabetic Retinopathy
Gestational, 50, 200 Gland, 176, 191, 200, 219, 222, 230, 233, 235 Glomerular, 46, 54, 59, 87, 137, 200, 207, 208, 228 Glomerular Filtration Rate, 54, 200, 208 Glomeruli, 40, 200 Glomerulosclerosis, 62, 200 Glomerulus, 200 Glucocorticoid, 192, 200, 236 Glucose Intolerance, 192, 200 Glucose tolerance, 18, 48, 152, 200 Glucose Tolerance Test, 152, 200, 201 Glutamate, 15, 19, 21, 26, 41, 83, 201, 213 Glutamic Acid, 201, 216, 224 Glycerol, 201, 221 Glycerophospholipids, 201, 221 Glycine, 19, 182, 201, 216, 231 Glycoprotein, 80, 89, 198, 201, 209 Governing Board, 201, 223 Grade, 20, 49, 61, 145, 201 Grading, 19, 21, 83, 90, 108, 201 Grafting, 201, 205 Granule, 201, 230 Granulocytes, 201, 232, 239 Growth factors, 32, 36, 59, 62, 90, 91, 201, 213 Guanylate Cyclase, 201, 216 H Haematoma, 201 Haemorrhage, 88, 201 Haptens, 176, 201 Headache, 177, 201 Health Care Costs, 22, 202 Health Education, 58, 163, 202 Health Expenditures, 202 Health Services, 192, 202, 234 Heart attack, 184, 202 Heart failure, 202, 217, 226 Hematocrit, 17, 183, 202 Hematopoiesis, 64, 202 Hemochromatosis, 72, 202 Hemodialysis, 202, 208 Hemodynamics, 17, 112, 202 Hemoglobin, 4, 5, 8, 12, 21, 30, 89, 178, 183, 197, 202, 209, 219 Hemoglobin A, 30, 89, 202 Hemoglobinopathies, 200, 202 Hemolysis, 197, 202 Hemorrhage, 4, 6, 11, 24, 102, 112, 144, 202, 203, 226, 233 Hemostasis, 203, 206, 231
Heparan Sulfate Proteoglycan, 98, 203 Hepatic, 176, 200, 203 Hepatocyte, 14, 77, 92, 203 Hepatocyte Growth Factor, 14, 77, 203 Hereditary, 59, 203, 229 Heredity, 152, 199, 200, 203 Heterodimer, 64, 133, 203 Heterogeneity, 17, 176, 203 Heterozygotes, 193, 203 Histology, 34, 38, 56, 203 Homeostasis, 37, 41, 50, 67, 203 Homogeneous, 17, 180, 203 Homologous, 40, 177, 191, 199, 203, 231, 234 Homozygotes, 193, 203 Hormonal, 190, 203 Hormone, 7, 16, 83, 86, 91, 102, 190, 191, 194, 196, 199, 203, 206, 209, 230, 231, 234, 235 Hybrid, 40, 203 Hybridomas, 203, 207 Hydrogen, 133, 137, 175, 182, 184, 185, 192, 198, 203, 204, 210, 214, 216, 219, 225 Hydrogen Peroxide, 185, 204, 210 Hydrolysis, 195, 204, 221, 223, 225, 236 Hydrophobic, 201, 204, 210 Hydroxylysine, 188, 204 Hydroxyproline, 188, 204 Hypercholesterolemia, 194, 204 Hyperglycemia, 10, 11, 20, 32, 35, 40, 46, 59, 135, 204 Hyperlipidemia, 11, 94, 194, 204 Hyperopia, 204, 228 Hyperoxia, 39, 94, 204 Hypersensitivity, 204, 209, 230 Hypertension, 5, 6, 11, 21, 23, 57, 58, 94, 180, 184, 195, 202, 204, 224, 229 Hypertriglyceridemia, 194, 204 Hypertrophy, 20, 35, 190, 204, 236 Hypesthesia, 204, 215 Hypoglycemia, 152, 204 Hypoglycemic, 8, 10, 204 Hypoglycemic Agents, 10, 204 Hypotension, 81, 189, 204 Hypoxia, 4, 13, 27, 30, 31, 53, 56, 63, 64, 67, 204 Hypoxic, 30, 52, 64, 178, 204 I Immune response, 51, 179, 181, 190, 191, 201, 204, 205, 233, 238 Immune system, 182, 204, 205, 210, 211, 214, 237, 239
247
Immunity, 204, 207, 217 Immunohistochemistry, 46, 66, 204 Immunologic, 186, 205, 220, 227 Immunology, 40, 140, 176, 205 Immunomodulator, 138, 205 Immunosuppressant, 205, 213 Impairment, 4, 10, 31, 56, 58, 69, 80, 86, 92, 198, 205 Implant radiation, 205, 207, 208, 227, 239 Implantation, 138, 189, 205 Impotence, 197, 205 In situ, 33, 36, 46, 68, 72, 145, 205 In Situ Hybridization, 33, 36, 46, 205 In vitro, 20, 21, 29, 32, 35, 36, 40, 43, 44, 46, 48, 51, 59, 68, 138, 200, 205, 230 In vivo, 20, 21, 26, 33, 36, 38, 43, 46, 48, 51, 57, 59, 65, 67, 112, 131, 140, 200, 205, 235 Incision, 205, 207 Incontinence, 17, 205 Incubation, 46, 205 Induction, 15, 20, 40, 46, 50, 138, 178, 205 Infancy, 205 Infantile, 39, 205 Infarction, 129, 205 Infection, 51, 152, 181, 182, 186, 187, 198, 205, 211, 216, 230, 233, 239 Infiltration, 51, 133, 205, 209 Informed Consent, 22, 206 Infusion, 112, 206 Ingestion, 5, 200, 206 Initiation, 43, 68, 206, 235 Initiator, 62, 206, 207 Inner ear, 206, 237 Inositol, 206, 213 Inotropic, 193, 206 Insight, 25, 67, 121, 206 Insulin, 5, 7, 9, 10, 12, 23, 35, 50, 58, 87, 88, 94, 98, 110, 113, 129, 151, 152, 200, 206, 219, 236 Insulin-dependent diabetes mellitus, 87, 94, 98, 110, 151, 206 Insulin-like, 35, 87, 88, 113, 206 Integrins, 133, 206 Intercellular Adhesion Molecule-1, 70, 206 Interferon, 96, 131, 199, 206, 207 Interleukin-1, 131, 207 Interleukin-12, 131, 207 Interleukin-2, 131, 207 Interleukin-6, 95, 207 Internal Medicine, 8, 11, 14, 88, 97, 207 Internal radiation, 207, 208, 226, 239 Interstitial, 183, 198, 207, 208, 228, 239
Intervention Studies, 58, 207 Intestinal, 184, 196, 200, 207, 239 Intestinal Mucosa, 207, 239 Intestines, 129, 175, 199, 207 Intracellular, 16, 19, 26, 32, 38, 40, 42, 137, 205, 206, 207, 212, 213, 216, 223, 225, 231 Intramuscular, 207, 219, 236 Intraocular, 30, 34, 64, 77, 138, 195, 207, 217, 235, 238 Intraocular pressure, 30, 34, 64, 138, 207, 217, 235 Intravascular, 51, 207, 209 Intravenous, 198, 206, 207, 219 Intrinsic, 46, 176, 182, 207 Inulin, 200, 207 Invasive, 13, 17, 24, 30, 31, 44, 57, 204, 207, 211, 219 Involuntary, 207, 215 Ion Channels, 16, 181, 207 Ions, 182, 193, 194, 203, 208 Iridis, 87, 208 Iris, 36, 179, 190, 208, 223, 226, 237 Irradiation, 136, 208, 239 Ischemia, 20, 21, 23, 27, 52, 65, 67, 120, 208, 218 K Kb, 156, 208 Keto, 14, 208 Kidney Disease, 7, 116, 156, 208 Kidney Failure, 53, 196, 200, 208 Kidney Failure, Acute, 208 Kidney Failure, Chronic, 208 Kidney Transplantation, 74, 208 Kinetic, 14, 208 L Labile, 188, 208 Laminin, 36, 66, 133, 182, 198, 209 Large Intestine, 192, 207, 209, 227, 232 Laser Coagulation, 43, 209 Laser Surgery, 163, 164, 209 Laser therapy, 8, 128, 209 Latent, 15, 69, 209, 224 Laxative, 176, 209, 232 Least-Squares Analysis, 209, 228 Lens, 14, 36, 52, 67, 86, 129, 179, 180, 185, 199, 209, 238 Leptin, 96, 209 Lesion, 56, 66, 209, 210 Lethal, 138, 209 Leukemia, 52, 193, 200, 209 Leukemic Infiltration, 209 Leukostasis, 70, 209
248
Diabetic Retinopathy
Leukotrienes, 180, 194, 209 Ligaments, 190, 210 Ligands, 47, 137, 138, 206, 210 Light microscope, 210, 213 Likelihood Functions, 210, 228 Linear Models, 210, 228 Linkage, 26, 210, 221 Lipid, 43, 47, 92, 98, 180, 201, 206, 208, 210, 214, 219, 236 Lipid Peroxidation, 210, 219 Lipophilic, 44, 132, 210 Lipoprotein, 80, 92, 98, 108, 194, 210, 211 Lipoprotein(a), 92, 98, 210 Liver, 175, 176, 180, 182, 187, 199, 200, 202, 203, 209, 210, 228, 230 Liver scan, 210, 230 Localization, 29, 38, 69, 204, 210 Localized, 29, 37, 39, 68, 201, 205, 209, 210, 217, 222 Logistic Models, 61, 210, 228 Longitudinal Studies, 9, 44, 210 Loop, 28, 37, 211 Low vision, 27, 69, 211 Low-density lipoprotein, 194, 210, 211 Lucida, 209, 211 Luciferase, 33, 211 Lymph, 187, 190, 196, 211 Lymphatic, 196, 205, 211, 213, 217, 232 Lymphatic system, 211, 232 Lymphocytes, 38, 179, 199, 203, 207, 211, 215, 239 Lymphoid, 179, 211 Lysine, 46, 57, 204, 211, 236 Lysophospholipids, 43, 211 M Macrophage, 207, 211 Macula, 45, 66, 198, 211 Macula Lutea, 211 Magnetic Resonance Imaging, 211, 212, 230 Magnetic Resonance Spectroscopy, 56, 211 Malignant, 28, 179, 180, 212, 215, 227 Malnutrition, 176, 212 Mammary, 133, 212 Mammogram, 183, 212, 213 Manifest, 36, 41, 66, 212 Matrix metalloproteinase, 35, 36, 45, 212 Medial, 180, 212, 218 Mediate, 15, 47, 59, 112, 193, 212 Mediator, 38, 50, 52, 64, 207, 212, 231 Medical Records, 7, 50, 212
Medicament, 140, 212 MEDLINE, 8, 157, 212 Meiosis, 212, 234 Melanin, 208, 212, 221, 236 Melanocytes, 212 Melanoma, 28, 212 Membrane Lipids, 212, 221 Menorrhagia, 4, 212 Menstruation, 4, 138, 191, 212 Mental, iv, 12, 156, 158, 186, 193, 213, 226, 228, 237 Mental Health, iv, 12, 156, 158, 213, 226 Mesenchymal, 45, 62, 213 Mesoderm, 213, 239 Metabolite, 42, 213, 224 Metabotropic, 15, 213 Metastasis, 14, 60, 133, 140, 212, 213 Metastatic, 35, 141, 213, 230 Metastatic cancer, 35, 141, 213 Methotrexate, 68, 213 Mice, Transgenic, 57, 213 Microbe, 213, 235 Microbiology, 175, 213 Microcalcifications, 183, 213 Microcirculation, 47, 77, 92, 213, 222 Microglia, 181, 213 Microorganism, 187, 213, 220, 238 Microscopy, 46, 86, 182, 213 Microsurgery, 145, 213 Migration, 14, 29, 37, 43, 51, 59, 60, 133, 140, 206, 214 Mineralocorticoids, 176, 190, 214 Mitochondrial Swelling, 214, 215 Mitosis, 138, 180, 214 Mobility, 27, 69, 214 Modeling, 38, 194, 214 Modification, 46, 200, 214, 226 Modulator, 67, 214 Molecule, 20, 44, 131, 133, 179, 182, 187, 188, 193, 194, 196, 197, 202, 204, 214, 219, 227, 231, 233, 237 Monitor, 22, 44, 50, 164, 191, 214, 216 Monoclonal, 141, 203, 208, 214, 227, 239 Monocyte, 41, 214 Mononuclear, 41, 214 Morphological, 57, 150, 195, 212, 214 Morphology, 33, 40, 44, 185, 214 Motility, 51, 214, 231 Mucinous, 199, 214 Multiple sclerosis, 214, 218 Mutagenesis, 14, 33, 214 Mutagens, 214
249
Mydriatic, 78, 84, 193, 215 Myocardial infarction, 129, 190, 215, 239 Myocardium, 51, 215 Myopia, 215, 228, 229 N Natural killer cells, 207, 215 Nausea, 177, 215, 237 NCI, 1, 155, 187, 215 Necrosis, 90, 131, 180, 195, 205, 215 Neonatal, 46, 215 Neoplasia, 130, 139, 215 Neoplasm, 215, 236 Neoplastic Processes, 4, 215 Nephropathy, 8, 18, 35, 40, 49, 53, 93, 94, 98, 102, 129, 130, 137, 151, 152, 208, 215 Nervous System, 176, 186, 212, 215, 220, 234 Networks, 19, 56, 63, 215 Neural, 55, 113, 176, 213, 215, 229 Neuritis, 64, 215, 218 Neuronal, 20, 26, 41, 215 Neurons, 26, 38, 41, 47, 192, 197, 215, 234 Neuropathy, 8, 18, 40, 120, 129, 130, 137, 152, 177, 215 Neuroretinitis, 216, 229 Neurotoxin, 41, 216 Neurotransmitter, 21, 175, 183, 185, 193, 201, 208, 216, 231, 233 Neutrons, 177, 208, 216, 226 Neutrophil, 206, 216 Night Blindness, 216, 229 Nitric Oxide, 56, 96, 117, 216 Nitrogen, 178, 180, 198, 208, 216, 236 Norepinephrine, 176, 193, 216 Nuclear, 47, 50, 61, 182, 195, 197, 199, 215, 216, 229 Nuclei, 177, 195, 199, 200, 211, 214, 216, 218, 225 Nucleic acid, 205, 214, 216, 226 Nucleus, 180, 186, 191, 192, 195, 197, 211, 212, 213, 214, 216, 224, 225 O Observational study, 113, 216 Occult, 63, 217 Ocular Hypertension, 138, 217 Oedema, 77, 111, 217 Oligo, 66, 217 Oliguria, 208, 217 Omega-3 fatty acid, 119, 217 Oncogene, 203, 217 Oncogenic, 206, 217 Opacity, 185, 217
Open Reading Frames, 51, 217 Ophthalmic, 7, 22, 23, 44, 74, 75, 77, 91, 95, 96, 104, 110, 113, 114, 121, 134, 136, 217, 229 Ophthalmic Artery, 217, 229 Ophthalmologic, 6, 8, 34, 61, 217 Ophthalmologist, 7, 53, 55, 217 Ophthalmoscope, 33, 66, 217, 218 Ophthalmoscopy, 10, 163, 217 Opsin, 217, 229, 230 Optic Atrophy, 56, 217 Optic Chiasm, 218 Optic disc, 45, 218 Optic Disk, 211, 217, 218 Optic Nerve, 6, 30, 63, 177, 216, 217, 218, 229, 230 Optic nerve head, 30, 216, 218 Optic Neuritis, 64, 218 Optometry, 78, 84, 218 Orbital, 218 Organ Culture, 46, 218 Orthostatic, 81, 218 Osmotic, 176, 214, 218 Osteoporosis, 133, 218 Outpatient, 50, 218 Ovarian Follicle, 190, 218 Ovary, 190, 218, 219 Overexpress, 57, 219 Ovum, 190, 191, 200, 218, 219 Oxidation, 179, 191, 210, 219 Oxidative Stress, 21, 33, 219 Oximetry, 30, 55, 219 Oxygenation, 30, 38, 56, 63, 219 P Palliative, 26, 219, 234 Pancreas, 74, 83, 175, 202, 206, 219, 236 Pancreas Transplant, 83, 219 Pancreas Transplantation, 83, 219 Parenteral, 43, 219 Paresis, 215, 219 Paresthesias, 215, 219 Parietal, 219, 223 Particle, 219, 235 Parturition, 138, 219 Patch, 47, 219 Pathogen, 205, 220 Pathologic, 30, 35, 175, 180, 182, 190, 204, 209, 220, 225 Pathologic Processes, 35, 180, 220 Pathologies, 29, 40, 44, 50, 220 Pathophysiology, 4, 55, 80, 148, 220
250
Diabetic Retinopathy
Patient Education, 49, 162, 164, 168, 170, 174, 220 Patient Selection, 4, 220 Pentoxifylline, 120, 220 Peptide, 5, 13, 27, 43, 114, 132, 196, 198, 209, 220, 223, 225 Perception, 27, 192, 220 Percutaneous, 54, 220 Perfusion, 17, 23, 47, 68, 204, 220 Pericytes, 20, 45, 47, 67, 220 Periodontal disease, 35, 220 Peripheral Nervous System, 196, 216, 220, 233 Peripheral Vascular Disease, 49, 220 Peripheral vision, 132, 221, 238 Peritoneal, 181, 217, 221 Peritoneal Cavity, 181, 217, 221 Perivascular, 59, 213, 221 Petechiae, 201, 221 Pharmacokinetic, 49, 221 Pharmacologic, 45, 104, 178, 221, 235 Phenotype, 20, 60, 221 Phenylalanine, 221, 236 Phorbol, 51, 221 Phosphatidic Acids, 211, 221 Phosphodiesterase, 220, 221 Phospholipases, 221, 231 Phospholipids, 43, 198, 206, 210, 212, 221 Phosphorus, 184, 221 Phosphorylated, 29, 187, 221 Phosphorylation, 40, 221 Photodynamic therapy, 63, 136, 221 Photoreceptor, 38, 84, 221, 230 Physiologic, 19, 29, 176, 182, 207, 212, 221, 224, 227 Physiology, 16, 17, 20, 58, 163, 222 Pigment, 32, 36, 49, 65, 99, 110, 182, 212, 222, 229, 238 Pigmentation, 222, 238 Pilot study, 27, 31, 222 Pituitary Gland, 190, 198, 222 Placenta, 29, 113, 140, 222 Plana, 78, 96, 103, 222 Plants, 184, 199, 200, 207, 214, 216, 222, 223, 235 Plaque, 37, 222 Plasma cells, 179, 222 Plasma protein, 176, 196, 222 Plasmin, 14, 37, 222 Plasminogen Activator Inhibitor 1, 95, 222 Plasminogen Activators, 37, 222 Platelet Activation, 222, 232
Platelet Aggregation, 133, 178, 216, 220, 222, 235 Platelets, 129, 216, 222, 231, 235 Pleura, 223 Pleural, 141, 217, 223 Pleural cavity, 217, 223 Pneumonia, 189, 223 Polymorphic, 89, 186, 223 Polymorphism, 75, 86, 98, 100, 102, 129, 150, 223 Polypeptide, 177, 188, 198, 222, 223 Polysaccharide, 179, 223, 225 Polyunsaturated fat, 121, 223, 235 Posterior, 44, 67, 186, 193, 208, 218, 219, 223, 230 Posterior chamber, 67, 223 Postmenopausal, 218, 223 Postnatal, 223, 233 Postoperative, 4, 223 Postsynaptic, 223, 231 Potassium, 26, 214, 223 Potentiates, 207, 223 Potentiation, 223, 232 Practice Guidelines, 158, 223 Preclinical, 49, 223 Precursor, 29, 39, 45, 51, 178, 180, 193, 194, 195, 196, 216, 221, 223, 224, 236 Predisposition, 129, 224 Preeclampsia, 65, 224 Prenatal, 195, 224 Presynaptic, 21, 216, 224 Prevalence, 5, 7, 8, 11, 17, 21, 23, 34, 58, 80, 104, 105, 109, 110, 116, 117, 224 Probe, 50, 55, 224 Prodrug, 128, 129, 224 Professional Practice, 218, 224 Progressive, 4, 33, 36, 94, 163, 180, 185, 187, 194, 208, 215, 222, 224, 226, 228, 229, 236 Projection, 192, 216, 218, 224 Proliferative Retinopathy, 5, 6, 11, 27, 52, 164, 224 Proline, 188, 204, 224 Promoter, 24, 33, 224 Prone, 23, 224 Prophase, 224, 234 Prophylaxis, 137, 224, 239 Proportional Hazards Models, 50, 224 Prospective study, 58, 224 Prostaglandin, 21, 94, 224, 235 Prostaglandins A, 21, 224, 225 Prostaglandins D, 225
251
Protease, 140, 225 Protein C, 176, 177, 180, 210, 225 Protein Isoforms, 177, 225 Protein S, 182, 225, 230 Proteinuria, 73, 79, 200, 224, 225 Proteoglycans, 182, 198, 225 Proteolytic, 15, 188, 196, 198, 222, 225 Protocol, 18, 19, 63, 71, 106, 225 Protons, 177, 203, 211, 225, 226 Proximal, 47, 193, 224, 225 Psoriasis, 14, 130, 132, 133, 137, 138, 139, 140, 225 Public Health, 19, 22, 58, 135, 158, 226 Public Policy, 157, 226 Publishing, 4, 70, 152, 226 Pulmonary, 48, 62, 183, 190, 208, 209, 226, 237, 239 Pulmonary Artery, 183, 226, 237 Pulmonary Edema, 208, 226 Pulmonary Embolism, 226, 239 Pulmonary Fibrosis, 48, 62, 226 Pulmonary hypertension, 190, 226 Pulse, 195, 214, 219, 226 Pupil, 28, 163, 190, 193, 215, 218, 226 Purines, 226, 231 Purpura, 201, 226 Pyrimidines, 226, 231 Q Quality of Life, 8, 32, 110, 147, 226 Quiescent, 37, 51, 138, 226 R Race, 17, 48, 49, 214, 226 Radiation, 128, 136, 175, 184, 195, 197, 199, 207, 208, 226, 227, 230, 239 Radiation therapy, 175, 184, 197, 207, 208, 226, 239 Radioactive, 183, 203, 205, 207, 208, 210, 216, 217, 226, 227, 230, 239 Radiolabeled, 208, 227, 239 Radiological, 220, 227 Radiotherapy, 183, 208, 227, 239 Random Allocation, 227 Randomization, 22, 227 Randomized, 6, 22, 31, 49, 54, 63, 194, 227 Randomized clinical trial, 6, 227 Reactive Oxygen Species, 32, 227 Reagent, 211, 227 Recombinant, 15, 37, 49, 65, 130, 131, 139, 227, 237 Recombination, 40, 199, 227 Rectum, 179, 192, 199, 205, 209, 227 Recurrence, 24, 227
Reductase, 14, 79, 81, 114, 129, 137, 150, 177, 213, 227 Refer, 1, 53, 188, 195, 210, 211, 216, 228, 235 Reference Standards, 78, 228 Refraction, 21, 215, 228 Refractive Errors, 177, 228 Refractive Power, 215, 218, 228 Regeneration, 133, 198, 228 Regimen, 9, 50, 194, 228 Regression Analysis, 26, 228 Rehabilitative, 22, 228 Reliability, 11, 31, 64, 83, 106, 228 Remission, 227, 228 Renal failure, 11, 228 Renin, 23, 53, 104, 106, 109, 178, 228 Renin-Angiotensin System, 23, 104, 228 Respiration, 184, 214, 228 Retinae, 21, 211, 229 Retinal Artery, 30, 77, 229 Retinal Detachment, 6, 24, 38, 144, 229, 238 Retinal Ganglion Cells, 16, 218, 229 Retinal Hemorrhage, 6, 229 Retinal Neovascularization, 36, 49, 63, 65, 67, 100, 229 Retinal pigment epithelium, 33, 229 Retinal Vein, 21, 63, 229 Retinal Vein Occlusion, 21, 63, 229 Retinal Vessels, 52, 57, 66, 229 Retinitis, 38, 64, 138, 229 Retinitis Pigmentosa, 38, 64, 138, 229 Retinol, 229, 230 Retrobulbar, 218, 230 Retroviral vector, 199, 230 Rheology, 220, 230 Rheumatoid, 29, 35, 39, 40, 45, 58, 130, 131, 139, 140, 230 Rheumatoid arthritis, 29, 35, 39, 40, 45, 58, 130, 131, 139, 140, 230 Rhodopsin, 217, 229, 230 Ribose, 46, 230 Ribosome, 68, 230, 236 Ristocetin, 230, 237 Rod, 181, 221, 230 S Scans, 19, 230 Sclera, 68, 186, 189, 230, 237 Sclerosis, 132, 133, 180, 214, 230 Secondary tumor, 213, 230 Secretion, 35, 140, 190, 206, 213, 214, 230 Segmental, 200, 231
252
Diabetic Retinopathy
Segregation, 227, 231 Self Care, 175, 231 Senile, 218, 231 Sensor, 28, 231 Sequence Homology, 65, 231 Serine, 19, 65, 231, 236 Serine Endopeptidases, 231 Serine Proteinase Inhibitors, 65, 231 Serotonin, 216, 231, 236 Serous, 196, 223, 231 Serum, 12, 29, 35, 80, 92, 95, 97, 100, 108, 113, 121, 176, 178, 188, 208, 211, 214, 231 Sex Characteristics, 176, 178, 231, 234 Sharpness, 231, 238 Side effect, 56, 68, 129, 134, 135, 144, 147, 176, 182, 231, 235 Signal Transduction, 40, 140, 206, 231 Skeleton, 134, 175, 224, 232 Skull, 232, 234 Small intestine, 187, 194, 203, 207, 232, 236 Smooth muscle, 23, 24, 37, 43, 45, 178, 189, 220, 228, 232, 233 Social Environment, 226, 232 Soft tissue, 183, 232 Solid tumor, 29, 58, 60, 140, 178, 193, 196, 232 Soma, 16, 232 Somatic, 39, 176, 195, 212, 214, 220, 232 Somatic cells, 212, 214, 232 Somatic mutations, 39, 232 Sorbitol, 104, 129, 137, 177, 232 Specialist, 11, 31, 165, 193, 232 Species, 13, 23, 33, 59, 196, 203, 212, 213, 214, 226, 227, 231, 232, 233, 236, 238, 239 Specificity, 14, 29, 53, 108, 133, 140, 176, 232 Spectroscopic, 44, 211, 232 Sperm, 178, 186, 232 Spinal cord, 181, 186, 199, 215, 220, 232 Stabilization, 33, 37, 46, 63, 233 Staging, 230, 233 Statistically significant, 48, 233 Stem Cells, 51, 233 Stereoscopic, 8, 19, 26, 53, 83, 233 Steroids, 190, 200, 233 Stimulus, 30, 177, 194, 197, 207, 219, 233, 234 Stomach, 129, 175, 192, 197, 199, 200, 203, 207, 209, 215, 221, 232, 233 Stool, 205, 209, 233 Stress, 4, 7, 12, 16, 17, 56, 68, 185, 191, 215, 219, 224, 230, 233
Stroke, 23, 53, 57, 156, 184, 233 Stroma, 36, 208, 233 Stromal, 36, 233 Subacute, 205, 233 Subclinical, 205, 233 Subconjunctival, 68, 233 Subcutaneous, 35, 141, 176, 194, 217, 219, 233 Subspecies, 232, 233 Substance P, 213, 230, 233 Substrate, 29, 33, 129, 133, 233 Substrate Specificity, 29, 233 Suppression, 29, 35, 91, 137, 190, 233 Survival Analysis, 224, 233 Sympathomimetic, 193, 196, 216, 234 Synapse, 176, 224, 234, 236 Synapsis, 234 Synaptic, 16, 41, 216, 232, 234 Synergistic, 23, 234 Systemic, 11, 46, 57, 58, 68, 86, 138, 179, 183, 196, 202, 205, 208, 217, 227, 234, 236, 237, 239 Systemic disease, 57, 234 Systolic, 5, 9, 12, 204, 234 Systolic blood pressure, 5, 9, 12, 234 T Telangiectasia, 59, 234 Telecommunications, 234 Telemedicine, 10, 45, 111, 234 Temporal, 38, 211, 234 Tendon, 199, 234 Testosterone, 227, 234 Therapeutics, 37, 43, 98, 117, 234 Threonine, 231, 234 Threshold, 42, 108, 197, 204, 234 Thrombin, 198, 222, 225, 234 Thrombocytes, 223, 235 Thrombosis, 80, 206, 225, 233, 235 Thromboxanes, 21, 180, 194, 235 Thyroid, 235, 236 Thyroxine, 176, 221, 235 Tolerance, 7, 48, 175, 200, 235 Tomography, 17, 44, 66, 103, 189, 212, 235 Tonometry, 163, 235 Tooth Preparation, 175, 235 Topical, 68, 138, 204, 235 Torsion, 205, 235 Toxaemia, 224, 235 Toxic, iv, 177, 191, 204, 216, 235, 237 Toxicity, 13, 51, 129, 138, 194, 230, 235 Toxicology, 158, 235 Toxin, 235
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Trace element, 186, 235 Traction, 112, 235 Transcription Factors, 60, 235 Transduction, 47, 140, 231, 235 Transfection, 29, 182, 199, 236 Transgenes, 51, 236 Translation, 68, 236 Translational, 105, 236 Transmitter, 41, 175, 181, 193, 207, 212, 216, 236 Transplantation, 74, 95, 141, 236 Trauma, 202, 215, 236 Triad, 18, 236 Triamcinolone Acetonide, 96, 236 Tricuspid Atresia, 190, 236 Triglyceride, 135, 204, 236 Trophic, 23, 236 Trypsin, 66, 196, 236 Tryptophan, 188, 231, 236 Tumor model, 131, 236 Tumour, 138, 199, 236 Type 2 diabetes, 22, 25, 72, 75, 91, 93, 95, 104, 110, 116, 236 Tyrosine, 134, 193, 236 U Urban Health, 22, 236 Urban Population, 236, 237 Uremia, 208, 228, 237 Urethra, 237 Urinary, 12, 16, 17, 54, 205, 217, 237 Urine, 10, 12, 35, 58, 59, 152, 179, 182, 191, 193, 205, 208, 217, 225, 237 Urokinase, 15, 140, 222, 237 Uterus, 190, 191, 195, 199, 212, 237 Uvea, 138, 195, 237 Uveitis, 138, 237 V Vaccine, 225, 237 Vagina, 212, 237 Vancomycin, 68, 237 Vascular Resistance, 54, 237 Vasoactive, 47, 237 Vasodilator, 183, 193, 237 Vector, 33, 51, 235, 237
Vein, 29, 30, 52, 55, 180, 207, 216, 229, 237 Venous, 30, 39, 78, 180, 182, 185, 217, 225, 236, 237, 239 Venous Thrombosis, 237, 239 Ventricle, 181, 190, 226, 234, 236, 237 Ventricular, 190, 236, 237 Venules, 183, 184, 196, 213, 237 Vertebral, 222, 238 Vertigo, 177, 238 Veterinary Medicine, 157, 238 Viral, 46, 217, 235, 238 Viral vector, 46, 238 Virulence, 235, 238 Virus, 200, 222, 230, 235, 238 Viscera, 232, 238 Visual Acuity, 11, 12, 34, 43, 53, 69, 71, 78, 102, 105, 132, 163, 173, 189, 238 Visual Cortex, 177, 238 Visual field, 61, 64, 69, 218, 229, 238 Vitelline Membrane, 238, 239 Vitrectomy, 3, 5, 6, 11, 71, 78, 96, 103, 111, 112, 136, 144, 163, 238 Vitreoretinal, 4, 24, 88, 145, 238 Vitreoretinopathy, Proliferative, 91, 238 Vitreous Body, 19, 186, 229, 238 Vitreous Humor, 56, 229, 238 Vitro, 21, 40, 68, 238 Vivo, 17, 21, 33, 239 Voltage-gated, 15, 239 W War, 88, 239 Warfarin, 99, 239 White blood cell, 179, 211, 214, 215, 216, 222, 239 Wound Healing, 36, 40, 58, 65, 130, 133, 139, 178, 198, 206, 212, 239 X Xenograft, 141, 178, 236, 239 X-ray, 14, 185, 189, 208, 212, 216, 226, 227, 230, 239 X-ray therapy, 208, 239 Y Yeasts, 221, 239 Yolk Sac, 25, 64, 239
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Diabetic Retinopathy
