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

HORMONE THERAPY A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R EFERENCES

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

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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright ©2003 by ICON Group International, Inc. Copyright ©2003 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1

Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Hormone Therapy: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-597-83930-1 1. Hormone Therapy-Popular works. I. Title.

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

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

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Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on hormone therapy. 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 HORMONE THERAPY ................................................................................ 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Hormone Therapy ......................................................................... 5 The National Library of Medicine: PubMed ................................................................................ 62 CHAPTER 2. NUTRITION AND HORMONE THERAPY .................................................................... 103 Overview.................................................................................................................................... 103 Finding Nutrition Studies on Hormone Therapy ...................................................................... 103 Federal Resources on Nutrition ................................................................................................. 105 Additional Web Resources ......................................................................................................... 105 CHAPTER 3. ALTERNATIVE MEDICINE AND HORMONE THERAPY .............................................. 107 Overview.................................................................................................................................... 107 National Center for Complementary and Alternative Medicine................................................ 107 Additional Web Resources ......................................................................................................... 108 General References ..................................................................................................................... 109 CHAPTER 4. DISSERTATIONS ON HORMONE THERAPY ................................................................ 111 Overview.................................................................................................................................... 111 Dissertations on Hormone Therapy ........................................................................................... 111 Keeping Current ........................................................................................................................ 111 CHAPTER 5. CLINICAL TRIALS AND HORMONE THERAPY ........................................................... 113 Overview.................................................................................................................................... 113 Recent Trials on Hormone Therapy ........................................................................................... 113 Keeping Current on Clinical Trials ........................................................................................... 132 CHAPTER 6. PATENTS ON HORMONE THERAPY ........................................................................... 135 Overview.................................................................................................................................... 135 Patents on Hormone Therapy .................................................................................................... 135 Patent Applications on Hormone Therapy ................................................................................ 139 Keeping Current ........................................................................................................................ 145 CHAPTER 7. BOOKS ON HORMONE THERAPY .............................................................................. 147 Overview.................................................................................................................................... 147 Book Summaries: Federal Agencies............................................................................................ 147 Book Summaries: Online Booksellers......................................................................................... 148 The National Library of Medicine Book Index ........................................................................... 150 Chapters on Hormone Therapy .................................................................................................. 150 CHAPTER 8. MULTIMEDIA ON HORMONE THERAPY .................................................................... 153 Overview.................................................................................................................................... 153 Bibliography: Multimedia on Hormone Therapy....................................................................... 153 CHAPTER 9. PERIODICALS AND NEWS ON HORMONE THERAPY ................................................. 155 Overview.................................................................................................................................... 155 News Services and Press Releases.............................................................................................. 155 Newsletter Articles .................................................................................................................... 159 Academic Periodicals covering Hormone Therapy..................................................................... 160 CHAPTER 10. RESEARCHING MEDICATIONS................................................................................. 161 Overview.................................................................................................................................... 161 U.S. Pharmacopeia..................................................................................................................... 161 Commercial Databases ............................................................................................................... 162 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 167 Overview.................................................................................................................................... 167 NIH Guidelines.......................................................................................................................... 167 NIH Databases........................................................................................................................... 169

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Other Commercial Databases..................................................................................................... 172 APPENDIX B. PATIENT RESOURCES ............................................................................................... 173 Overview.................................................................................................................................... 173 Patient Guideline Sources.......................................................................................................... 173 Finding Associations.................................................................................................................. 176 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 179 Overview.................................................................................................................................... 179 Preparation................................................................................................................................. 179 Finding a Local Medical Library................................................................................................ 179 Medical Libraries in the U.S. and Canada ................................................................................. 179 ONLINE GLOSSARIES................................................................................................................ 185 Online Dictionary Directories ................................................................................................... 185 HORMONE THERAPY DICTIONARY .................................................................................... 187 INDEX .............................................................................................................................................. 263

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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 hormone therapy 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 hormone therapy, 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 hormone therapy, 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 hormone therapy. 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 hormone therapy, 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 hormone therapy. 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 HORMONE THERAPY Overview In this chapter, we will show you how to locate peer-reviewed references and studies on hormone therapy.

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

Preliminary Study of Growth Hormone Therapy for Crohn's Disease Source: New England Journal of Medicine. 342(22): 1633-1637. June 1, 2000. Summary: Crohn's disease is a chronic inflammatory disorder of the bowel. This article reports on a preliminary study in which the authors evaluated whether the administration of growth hormone (somatropin) as well as a high protein diet would reduce or eliminate the symptoms of the disease. The authors randomly assigned 37 adults with moderate to severe active Crohn's disease to four months of self administered injections of growth hormone or placebo. All patients increased their protein intake to at least 2 g per kilogram of body weight per day. Patients continued to be treated by their usual physicians and to receive other medications for Crohn's disease. At baseline, the mean score on the Crohn's Disease Activity Index (CDAI) was

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somewhat higher among the 19 patients in the growth hormone group than among the 18 patients in the placebo group. Three patients in the placebo group withdrew before their first follow up visit and were not included in the data analysis. At four months, the CDAI score had decreased by a mean of 143 in the growth hormone group, as compared with a decrease of 19 points in the placebo group. Side effects in the growth hormone group included edema (in 10 patients) and headache (in 5 patients) and usually resolved within the first month of treatment. The authors conclude that their preliminary study suggests that growth hormone may be a beneficial treatment for patients with Crohn's disease. 4 tables. 20 references. •

Growth Hormone Therapy for Children with Kidney Failure Source: aakpRenalife. 14(5): 7, 31. Spring 1999. Contact: Available from American Association of Kidney Patients (AAKP). 100 South Ashley Drive, Suite 280, Tampa, FL 33602. (800) 749-AAKP or (813) 223-7099. E-mail: [email protected]. Website: www.aakp.org. Summary: Progressive growth retardation is an all too frequent characteristic of children on dialysis and children who receive a kidney transplant. This results in as many of 60 percent of these children developing marked short stature and attaining a final adult height at or below the third percentile on a standard growth chart. This article discusses the use of growth hormone therapy for children with kidney failure. Growth hormone (GH) is synthesized in the pituitary gland and indirectly promotes the growth of a child by stimulating the production of insulin like growth factor 1 (IGF 1). Paradoxically, many children with renal disease and growth retardation have normal or elevated levels of GH in their blood. By contrast, the levels of IGF 1 that are needed to stimulate growth are low. The article reports on the results using recombinant human growth hormone in these children. Recombinant human growth hormone appears to work by increasing the availability of IGF 1 to directly stimulate growth and is only administered to children with 'growth potential' as evidenced by open bone growth plates on x ray evaluation. Because of the growth inhibiting effects of uremia, together with the need for dialysis and steroids following transplantation, the provision of recombinant human growth hormone during the pre end stage renal disease period is likely the optimal approach when the goal is to prevent or correct the growth retardation that occurs in these children.

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Growth Hormone Therapy and Lipid Profile in Children on Chronic Peritoneal Dialysis Source: Pediatric Nephrology. 17(10): 830-836. October 2002. Contact: Available from Springer-Verlag. Service Center Secaucus, 44 Hartz Way, Secaucus, NJ 07094. (201) 348-4033. Summary: This article reports on a study that assessed the effect of recombinant human growth hormone (rhGH) on serum lipids (fats in the blood) in children treated with chronic peritoneal dialysis. The study included 26 patients aged 5 to 18 years, including 13 patients treated with rhGH (weekly for 6 months) and a control group of 13 patients. The authors found a significant increase in the triglyceride (TG) level after 1 month of administration of rhGH in the treatment group compared with both baseline and the control group at 1 month. The authors found no change in total cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol, apolipoproteins A-1, and lipoprotein total protein. The authors conclude that it is difficult to establish whether the effect of rhGH on the lipid profile in patients treated with peritoneal dialysis might

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stimulate development of atherosclerotic vascular lesions ('hardening of the arteries'). However, the observed elevation of TG level was only transient and short lived. 1 figure. 4 tables. 53 references. •

Postmenopausal Hormone Therapy and Cognitive Function in Healthy Older Women Source: JAGS. Journal of the American Geriatrics Society. 48(7): 746- 752. July 2000. Summary: This journal article examined the association of postmenopausal hormone therapy and cognitive performance in healthy older women. The sample consisted of 2,138 women aged 70-78 years from the Nurses' Health Study. Four cognitive tests were administered by telephone between 1995 and 1999. Hormone use was ascertained from questionnaires. After adjusting for confounders, neither current nor long-term hormone use was associated with better performance on an overall measure of cognition or on the three measures of verbal memory. However, current hormone users performed significantly better than never users on the test of verbal fluency. Results were similar for women taking estrogen alone and those taking estrogen and a progestin. The findings suggest that verbal fluency may be enhanced with postmenopausal hormone use, but there is little evidence of benefit for overall cognitive function. 3 tables, 35 references.

Federally Funded Research on Hormone Therapy The U.S. Government supports a variety of research studies relating to hormone therapy. 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 hormone therapy. 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 hormone therapy. The following is typical of the type of information found when searching the CRISP database for hormone therapy: •

Project Title: AGE RELATED SLEEP IMPAIRMENT--POSSIBLE INTERVENTIONS Principal Investigator & Institution: Vitiello, Michael V.; Professor and Senior Scientist; Psychiatry and Behavioral Scis; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2001; Project Start 01-AUG-1994; Project End 31-JUL-2004 Summary: This is a competing renewal of Dr. Michael V. Vitiello's NIMH Independent Scientist Award, K02-MH01158, Age-Related Sleep Disturbance Possible Interventions. As much as 40% of the older population complains of significant, chronic sleep disturbance. Sleep complaints often lead to chronic sedative hypnotic use and the

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

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elderly receive a disproportionate number of such prescriptions. Sedative-hypnotics offer short-term relief but their long-term efficacy is unclear and chronic use has been associated with increased morbidity and mortality. A recent NIH Consensus Conference concluded that chronic hypnotic use is inappropriate and that non-sedative interventions for sleep disruption are sorely needed. Dr. Vitiello proposes three specific aims that will examine possible non-sedative hypnotic approaches to improving the sleep quality of the elderly: Specific Aim 1: Examine the usefulness of fitness training interventions to improve the sleep quality of older men and women. Specific Aim 2: Examine the usefulness of neuroendocrine interventions (e.g., growth hormone releasing hormone, estrogen, and testosterone supplementation) to improve the sleep quality of older men and women. Specific Aim 3: Examine the usefulness of cognitive behavioral techniques to improve the sleep quality of older men and women in a number of different settings. While pursuing these aims, Dr. Vitiello will develop additional expertise in the interactions of sex steroids and sleep quality, ambulatory monitoring of sleep and respiration, actigraphic recording of rest/activity rhythms and cognitive behavioral interventions for sleep disturbance in the elderly. Each of these proposed lines of research has considerable significance for our understanding of the causes of,and potential treatments for, sleep disturbance in the aged. Effective nonsedative interventions may significantly improve not only sleep quality but also overall the quality of life in the elderly. Further, such interventions may have significant impact in decreasing morbidity and mortality directly related to such sleep disturbance or its inappropriate treatment with chronic hypnotic medications. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: AGING AND HYPERTENSION--GENDER, GENES AND RISK Principal Investigator & Institution: Fisher, Naomi D.; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2001; Project Start 30-SEP-1998; Project End 31-AUG-2003 Summary: (Adapted from applicant's abstract). This application is for a Mentored Clinical Scientist Development Award. The applicant states that that sexual dimorphisms in cardiovascular risk evolve with increasing age, and that women experience significantly less hypertension and heart disease than do men -- though this difference disappears with increasing age, especially among Blacks. The research plan in this proposal aims to pursue preliminary evidence which suggests that age, gender and race play a key role in modifying the ultimate expression of genetic risk. In particular, preliminary data reveal that females are protected against expression of a common intermediate phenotype of essential hypertension, marked by abnormal responsiveness to angiotensin II. And among the many genes proposed to cause human hypertension, one of the very few for which linkage has been documented is that coding for angiotensinogen (AGT), a key element of the renin-angiotensin system - yet linkage has been convincingly shown only in males. The present proposal aims to test the hypothesis that the ultimate expression of the AGT gene is strongly influenced by age, gender, and hormonal status. It will test whether female hormone replacement therapy (HRT) can confer the same protection as do endogenous sex steroid hormones; whether race influences the relationship between AGT genotype and the phenotype of AngII responsiveness; and whether nutritional factors, ultimately involving obesity, contribute. With anticipated award the applicant's plan is to continue clinical research in hypertension, applying techniques and understanding of renal and adrenal physiology to the process of aging. Controlled physiologic studies by her will be performed on the Clinical Research Center of the Brigham and Women's Hospital. As well, she will be

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mentored by Dr. Lewis Lipsitz who is experienced in cardiovascular function and disease in the aging populations. The applicant's stated goal is to establish for herself an independent research career path for studying cardiovascular, renal, and adrenal function in relation to the pathogenesis of hypertension in the elderly. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: AR SIGNALING IN HORMONE REFRACTORY PROSTATE CANCER Principal Investigator & Institution: Pinski, Jacek; Medicine; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2005 Summary: (provided by applicant): The androgen receptor (AR) mediates androgen signaling in the prostate and plays a vital role during all phases of prostate cancer development including the final androgen-independent phases. Somatic AR mutations, increased AR expression, increased AR coactivator expression and/or AR androgenindependent activity are all potential mechanisms causing prostate cancer progression to androgen-independent disease. Such aberrant AR activities might affect and/or predict time to hormone ablation therapy failure. Since clinical practice at present does not consider these mechanisms in choice or timing of treatment, we propose the use of aggressive chemotherapy and/or alternative androgen ablation treatments in conjunction with knowledge of the underlying mechanism of failure. We propose that response to chemo- or alternative hormone ablation therapy will be affected by the underlying AR mechanism of the original ablation therapy failure. In specific aim #1, we will measure AR mutations and expression levels of AR, p160 coactivators and HER2 in archival tissue from men in cohorts representing different stages of disease. In specific aim #2, we intend to do a preclinical trial using the CWR22 tumor model in mice to test early therapy and how it relates to the particular molecular abnormality biologically selected for during the course of androgen ablation treatment. Overall our work will provide a molecular framework of hormone resistant prostate cancer, important indices of prognosis, and the basis for several future clinical trials in alternative treatment strategies of androgen-independent prostate cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: BENEFITS OF TESTOSTERONE ON STRENGTH IN ELDERLY MEN Principal Investigator & Institution: Katznelson, Laurence; Assistant Professor; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2001; Project Start 01-AUG-1998; Project End 31-JUL-2003 Summary: (Adapted from the Applicant's Abstract): In this proposal, the effects of testosterone administration alone, or, in combination with exercise, on muscle function in elderly, sedentary men with testosterone deficiency will be investigated. Aging is associated with skeletal muscle sarcopenia and diminished muscle performance, which lead to significant disability from falls and loss of independence. One factor that may lead to sarcopenia is the presence of testosterone deficiency. Serum testosterone levels decrease progressively with age and the majority of elderly men have serum testosterone and free-testosterone levels below the mean for young men. Because testosterone deficiency may lead to alterations in body composition that include decreases in lean mass and strength, it is hypothesized that administration of testosterone therapy to older men with testosterone deficiency (relative to young men) may lead to improvements in muscle function and overall performance. In this proposal, 96 physically inactive elderly men with relative testosterone deficiency will be

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randomized in a double blind, placebo controlled fashion to receive testosterone enanthate therapy as intramuscular injections at a dose of 200 mg given every 2 weeks versus placebo for a total of 12 weeks. This study will test the hypothesis that administration of gonadal steroids will have a beneficial effect on lean muscle mass, muscle strength, and overall function. These men will be randomized further either to maintain the same level of physical inactivity or to undergo a graded resistance exercise program. This part of the protocol will test the hypothesis that the combined modalities of testosterone and exercise will have additive beneficial effects on muscle mass and function. The goal of these studies will be to determine the efficacy and safety of testosterone administration and, additionally, a home-based exercise program on muscle function in older men with relative testosterone insufficiency. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CARCINOGENICITY OF B RING UNSATURATED ESTROGENS Principal Investigator & Institution: Spink, David C.; Research Scientist; Wadsworth Center Empire State Plaza Albany, Ny 12237 Timing: Fiscal Year 2001; Project Start 07-JAN-2000; Project End 31-DEC-2003 Summary: The major concern regarding estrogen replacement therapy (ERT) is the significant increase in the risk of breast cancer that accompanies long-term use. The most commonly used formulation for ERT is Premarin, a preparation consisting largely of B-ring unsaturated estrogens including conjugated forms of equilin (Eq) and equilenin (Eqn). Our preliminary studies show Ah-receptor-regulated metabolism of Eqn to 4-hydroxylated metabolites in several human breast-derived cell lines expressing cytochrome P4501B1 (CYP1Bl). Semiquinones and quinones derived from these 4hydroxy metabolites, which are adductive and lead to free radical production, may be involved in carcinogenesis. We hypothesize that estrogens are involved in both the initiation and promotion phases of carcinogenesis, and that aromaticity of the B-ring of steroidal estrogens increases carcinogenic potency. Our broad, long-term goal is to determine whether steroidal estrogens, including the B-ring unsaturated estrogens, Eq and Eqn, are carcinogenic through metabolic activation via catechol estrogens. 0ur Specific Aims are to: 1) Characterize Eq and Eqn metabolism in a series of immortalized tumor- and non-tumor-derived human breast-cell lines. Pathways of Eq and Eqn bioactivation involving hydrolysis of conjugates, reduction to 17beta-dihydro forms and hydroxyation to catechol estrogens will be investigated. 2) Determine the catechol synthetic activities of human cytochromes P450 of the CYP1, CYP2, and CYP3 families with Eq, Eqn, and their 17alpha- and 17beta-dihydro forms as substrates. 3) Establish transgenic mouse lines expressing human CYP1B1 in the mammary epithelium, 4) Determine the effects of treatment with Eq and Eqn on DNA damage and the incidence of mammary-gland tumors in human CYP1B1-transgenic mice. The studies described here will provide novel results regarding the metabolism of the B-ring unsaturated estrogens by human enzymes in breast epithelial cells, and may provide mechanistic data supporting a role of metabolic activation of Eq, Eqn, and endogenous in the initiation of carcinogenesis in the human breast. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CEREBRAL ISCHEMIA IN THE FEMALE Principal Investigator & Institution: Hurn, Patricia D.; Professor and Vice Chairman for Research; Anesthesiology/Crit Care Med; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218

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Timing: Fiscal Year 2001; Project Start 01-FEB-1995; Project End 31-JAN-2004 Summary: In this animal research protocol, the investigators propose to ascertain the cerebral blood flow and metabolic effects of the presumed neuroprotective female hormones during and following global cerebral ischemia. Specifically, the proposed study will determine the effect of global cerebral ischemia on cerebral blood flow (CBF), energy metabolism, and pial vessel reactivity in female animals compared to their male counterparts. The investigators also will evaluate whether or not the female hormone, beta- estradiol, plays an important role in recovery mechanisms from ischemia. Unneutered males also will be studied to determine if there are important gender-specific recovery responses during ischemia/reperfusion and if any therapeutic benefit from reproductive steroid administration is limited to females. The proposed experiments will explore two specific mechanisms of ischemic injury in vivo; specifically, 1) acidosis leading to depressed recovery of energy metabolism, loss of pH regulation, and related iron- catalyzed oxidant injury; and 2) microvascular endothelial dysfunction. To study these variables, the investigators will use magnetic resonance (MR) spectroscopy and intravital microscopy to determine if estradiol acts via specific cellular mechanisms. Four Specific Aims are presented. In Specific Aim #1, the investigators will test the hypothesis that ischemic acidosis is less in females, with consequently more complete recovery of brain energy phosphates compared to males; and that chronic estrogen therapy further improves post-ischemic recovery of energy metabolism and intracellular pH. Specific Aim #2 will examine the effect of pre-ischemic hyperglycemia and its consequent exaggerated tissue acidosis on metabolic recovery, testing the hypothesis that the anti- oxidant activity of estradiol decreases vulnerability to hyperglycemiamediated reperfusion injury. Intravital microscopy will be employed in Specific Aim #3 to determine if post-ischemic pial vessel reactivity to endothelium-dependent pharmacologic agents is impaired in females and estradiol-treated animals. Finally, Specific Aim #4 will test the hypothesis that chronic estradiol therapy increases brain cGMP, nitric oxide synthase activity and pial vessel responsivity to NO-mediated agents in a dose-dependent manner. The information derived from these experiments should contribute to our understanding of vascular function in females at decreased risk for cerebrovascular disease relative to males and of the role of estrogen as potential neuroprotective therapy for patients of either sex. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: COGNITION AND ESTROGEN IN MENOPAUSE:A MONKEY MODEL Principal Investigator & Institution: Voytko, Mary L.; Associate Professor; Pathology; Wake Forest University Health Sciences Winston-Salem, Nc 27157 Timing: Fiscal Year 2002; Project Start 01-MAY-1996; Project End 31-AUG-2007 Summary: (Provided by applicant): Ovarian hormone deficiency of menopause brings on changes that can have far reaching consequences on the future health and well being of women. Nondemented postmenopausal women frequently note alterations in cognitive functions, particularly memory and attention. Determining the relationship between ovarian hormones and cognitive function in menopause can be difficult to study in women because of a variety of confounding factors. We have developed a monkey model of menopause that allows us to more rigorously control many of these factors and additionally, that has allowed us to begin to identify cholinergic mechanisms of ovarian hormone action in the primate brain. Our initial behavioral and neurobiological studies were performed in young ovariectomized monkeys so that we could determine the effects of estrogen therapy (ERT) without the influence of other

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confounding factors, including advanced age. However, there are many important questions that remain unanswered, including the effects of estrogen plus progesterone therapy (HRT) and the effects of ovarian hormones in monkeys of an age that more closely models that of the middle-aged postmenopausal woman. These issues will be addressed in middle-aged monkeys in the present project. Behavioral experiments in Specific Aim 1 will determine the cognitive effects of ovarian hormone replacement therapy (ERT and HRT) using a series of behavioral tasks that measure several different cognitive functions that rely on the cholinergic system. In Specific Aim 2. functional imaging studies of the cholinergic system will be performed in the monkeys of Specific Aim 1 in parallel with their behavioral assessments to determine if measures of presynaptic cholinergic activity correlate with measures of cognitive function in monkeys treated with ovarian hormones. In Specific Aim 3. pharmacological studies will be performed in the monkeys following their initial behavioral and imaging studies to determine the effects of cholinergic, muscarinic and nicotinic receptor blockade on cognitive function in monkeys treated with ovarian hormones. Thus, the overall objectives of the experiments proposed in this application are to extend and broaden our initial investigations in young monkeys by determining the effects of ovarian hormone replacement therapy on cognitive function and in vivo cholinergic system function in middle-aged surgically menopausal rhesus monkeys. The findings from these novel experiments in middle-aged monkeys will significantly advance our understanding of the effects of ovarian hormone therapy on cognitive and neurobiological profiles of primates. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CONSEQUENCES OF MALE LH RECEPTOR GENE KNOCKOUT Principal Investigator & Institution: Lei, Zhenmin; Obstetrics and Gynecology; University of Louisville University of Louisville Louisville, Ky 40292 Timing: Fiscal Year 2001; Project Start 13-APR-2001; Project End 31-MAR-2003 Summary: (Provided by the Applicant) We recently succeeded in creating mice with the luteinizing hormone receptor gene knockout (LHRKO) by a homologous DNA recombination technology. Targeting deletion of the LHR gene at the promoter to exon one region completely inactivated the gene, which resulted in no detectable LHR in the gonads of homozygous animals. The LHR null males are not lethal but sterile, while their heterozygous littermates appear to be normal. The external and internal genitalia of homozygous males were grossly underdeveloped and spermatogenesis was arrested at the spermatocytes. The phenotype is believed to be caused by decreased androgen influence in the absence of LH stimulation of testicular Leydig cells. Testosterone replacement therapy, in spite of improvement in testicular morphology and spermatogenesis, did not restore male fertility, as homozygous males have very low sperm numbers and motility. In view of the fact that LH has pervasive actions, mediated by its receptors in gonadal and nongonadal tissues such as functional LHR in sperm and epididymis and with preliminary results obtained from LHRKO males, we hypothesize that the contribution of LH to spermatogenesis may be more than just acts on Leydig cells for androgen production. Having this unique LHRKO mouse model enables us to selectively investigate the crucial roles of LH in reproductive biology. This proposed research is aimed at searching for potential causes of infertility in LHRKO males even after androgen replacement therapy. Therefore, this small grant application will only focus on two aspects that are known to be critical in spermatogenesis and sperm maturation, listed as two specific aims: 1) investigating the effect of LHRKO on spermatogenic cells. 2) determining the effect of LHRKO on sperm maturation. These

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functional data are essential for us to further investigate the vital role of LH in male reproduction at biochemical and molecular levels. Infertility in human due to genetic defects in LHR or LH-p subunit are increasingly recognized, but there are no naturally occurring animal models with the corresponding mutations available for study. Thus, the data obtained from these LHRKO mice will not only advance our understanding on how important the actions of LH are for normal male reproductive physiology but will also facilitate developing better diagnostic and therapeutic options for male infertility and, conversely, developing more effective and safer male contraceptive reagents. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: COOPERATIVE MULTICENTER REPRODUCTIVE MEDICINE NETWORK Principal Investigator & Institution: Mc Govern, Peter G.; Ob/Gyn & Women's Health; Univ of Med/Dent Nj Newark Newark, Nj 07103 Timing: Fiscal Year 2001; Project Start 30-JUN-2000; Project End 31-MAR-2005 Summary: Infertility is a common problem in the United States. Technological advances have made therapy for infertility quite effective. However, all of the assisted reproductive techniques require the use of gonadotropins (whether recombinant or derived from menopausal urine) to induce ovulation. Serious complications of these therapies include multiple pregnancy, ovarian hyperstimulation syndrome (OHSS), and premature delivery (even in singletons). These complications exact a huge toll upon the physical, emotional and financial status of these couples, and place a major strain on the health care resources of our entire society. Our hypothesis is that the hypersecretion of luteal products (such as VEGF, renin and IL-6) caused by multiple corpora lutea is responsible for the development of OHSS. We also hypothesize that the hypersecretion of luteal products such as relaxin causes much of the prematurity associated with gonadotropin use. We have presented data that hyperrelaxinemia (in pregnancies conceived after the use of gonadotropins) correlates with prematurity. We have also demonstrated relaxin receptors in the human cervix, and that relaxin stimulates proMMP-1 and proMMP-3 expression as well as inhibiting TIMP-1 production, all effects which can contribute to increased collagen breakdown and cervical ripening. We plan to develop a method of superovulation which should result in luteal regression, which in turn should eliminate OHSS and decrease the risk of prematurity. This could have the secondary effect of making multiple pregnancies safer. hLH, with a much shorter half-life, will be substituted for hCG as the ovulatory stimulus. Pretreatment with a GnRH-agonist will eliminate endogenous LH secretion. The lack of continued luteotrophic stimulus will allow luteolysis. The endometrium will be maintained with exogenous estradiol and progesterone as is done in oocyte donation cycles. We will then test the hypothesis that this novel protocol, by preventing the hypersecretion of luteal products in gonadotropin-induced pregnancies, will result in safer infertility therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: COOPERATIVE MULTICENTER REPRODUCTIVE MEDICINE NETWORK Principal Investigator & Institution: Legro, Richard S.; Associate Professor; ObstetricsGynecology; Pennsylvania State Univ Hershey Med Ctr 500 University Dr Hershey, Pa 17033 Timing: Fiscal Year 2001; Project Start 30-JUN-2000; Project End 31-MAR-2005

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Summary: The overall hypothesis of this proposal is that insulin resistance is the fundamental pathophysiologic defect in women with polycystic ovary syndrome (PCOS), and therefore interventions to improve it are most likely to result in spontaneous ovulation and a singleton term pregnancy in infertile PCOS women. The primary aim is to identify the most effective form of ovulation induction in PCOS women that will result in a full term singleton intrauterine pregnancy with the safest profile. We propose to perform a multicenter-randomized trial of two methods of ovulation induction in clomiphene-resistant PCOS women (failure to either ovulate or conceive after an adequate trial of clomiphene). The women will be randomized to either gonadotropin or metformin treatment. Gonadotropins are the current standard method of ovulation induction in clomiphene resistant PCOS women and directly stimulate ovarian follicular development. The large cohort of arrested antral follicles and the unique pathophysiology of insulin resistance in PCOS places these women at particular risk for ovarian hyperstimulation syndrome (OHSS) and multiple pregnancy with this form of therapy. Metformin achieves ovulation through improvement in insulin sensitivity and suppression of hepatic gluconeogenesis. These changes induce secondary effects of decreased circulating insulin, androgens and gonadotropins, increased sex hormone binding globulin, and increased ovulatory function. PCOS women will be identified on the basis of unexplained hyperandrogenemic chronic anovulation, without other health problems, and no other major infertility factor. We hypothesize that the treatment arm that improves insulin sensitivity will be more likely to result in monofollicular ovulation and thus singleton pregnancy, and less likely to result in the complications of ovulation induction including multiple pregnancy and OHSS. This study could have a major impact on infertility in PCOS women while avoiding the risks and costly burden of OHSS and multiple pregnancy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DHEA EFFECTS ON MOOD IN DEPRESSED HIV+ PATIENTS Principal Investigator & Institution: Rabkin, Judith G.; Professor; New York State Psychiatric Institute 1051 Riverside Dr New York, Ny 10032 Timing: Fiscal Year 2001; Project Start 10-AUG-2000; Project End 31-JUL-2004 Summary: This is a double blind, placebo-controlled clinical trial of the antidepressant effect of DHEA among HIV+ individuals. Secondary goals will include determination of whether DHEA has anabolic effects or androgenic effects on enrolled subjects. The investigators will consider the basic endocrinology of adrenal steroid metabolism in the subjects, and propose to assess the effects of DHEA on immune status and viral activity with regard to the safety of the use of DHEA in HIV infected individuals. The study is an eight week double blind controlled trial of oral DHEA vs. placebo with an eight week maintenance phase for drug responders, and 16 weeks of open treatment offered to placebo non-responders (after the eight week double blind trial). They propose a 1:1 randomization and predict that 114 enrolled individuals will complete the eight week trial. If DHEA ameliorates depressive symptoms, as well as increasing libido and reducing loss of muscle mass, then the investigators will have identified an intervention with a broad spectrum of action suitable for both men and women with HIV infection, that is practical, inexpensive, and accessible. With regard to the endocrine studies, the investigators will assess precursors and metabolites of DHEA before and after oral administration of the compound, and examine effects of cortisol, triglycerides, insulin, cholesterol, growth hormone, IGF-1, and IGF-1 binding proteins. Tests will be administered at study baseline, weeks 4 and 8, including standard dose ACTH, low dose ACTH, CRF, and GNRH stimulation tests to assess the hypothalamic-pituitary-

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adrenal and hypothalamic-pituitary gonadal function before and after DHEA administration. This will permit the investigators to assess potential underlying mechanisms for the putative therapeutic effects of DHEA on mood, libido, and body composition. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DHEA REPLACEMENT IN HEALTHY OLDER MEN AND WOMEN Principal Investigator & Institution: Goodman-Gruen, Deborah L.; Family and Preventive Medicine; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, Ca 92093 Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 31-AUG-2005 Summary: (adapted from Investigator's abstract) Levels of dehydroepiandrosterone (DHEA) and DHEA-sulfate (DHEAS), the major secretory product of the adrenal gland, decrease dramatically with age, concurrent with the onset of degenerative changes and chronic diseases associated with aging. Epidemiological evidence in humans and numerous animal studies have suggested that DHEA(S) has cardioprotective, antiobesity, antidiabetic, immuno-enhancing, and cancer-preventing properties. These observations have led to the proposal that restoration of DHEA levels in older adults to those of young adults may offer protection from age-associated health deficits. To date, clinical trials of DHEA replacement have been limited due to small sample size, lack of adequate power, restriction to one gender, failure to adjust for potential confounders (baseline endogenous hormone levels and age), lack of placebo comparison groups, and short duration of administration. This double blind, placebo-controlled randomized trial will determine the acceptability, benefits, and adverse effects of 50 mg daily oral DHEA replacements for one year in 100 men and 100 women, 55 to 85 years of age, who are healthy and not currently using any hormone therapy. Data will be collected at a screening visit, baseline visit, and at three follow-up visits over the course of one year. A wide range or biological outcomes will be studied including bone mineral density and metabolism, body composition and muscle strength, immune function, and cardiovascular risk factors. Central effects of DHEA will be investigated by assessing changes in mood and well-being, cognitive function, and sexuality. Cross-sectional and longitudinal analyses comparing the treatment and placebo groups on each health outcome will be adjusted for potentially confounding covariates such as smoking, alcohol consumption, exercise, diet, and supplements and the influence of gender, age and baseline endogenous DHEA level on each outcome variable will be examined. Potential mechanisms of DHEA action will be studied including biotransformation of DHEA to active steroids and steroid metabolites, enhancement of IGF-1 bioavailability, and inhibition of IL-6 production. In addition, potential adverse effects of DHEA administration will be systematically monitored. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: DIET, HORMONE REPLACEMENT THERAPY AND BREAST CANCER Principal Investigator & Institution: Zhang, Shumin; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2003; Project Start 12-AUG-2003; Project End 31-JUL-2007 Summary: (provided by applicant): This is a resubmission of I K07 CA096619-01 "Diet, Hormone Replacement Therapy and Breast Cancer". Candidate: Shumin Zhang received her MD at the Harbin Medical University in 1986 and her ScD in epidemiology and

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nutrition at the Harvard School of Public Health in 1998. She then completed her postdoctoral training in 2000, and now is an Assistant Professor of Medicine at the Harvard Medical School (HMS). She applies for this Career Development Award to acquire the methodological and theoretical research skills needed to become an independent scientist in cancer and nutritional epidemiology. Sponsor and Environment: JoAnn Manson, MD, DrPH, is the Chief of the Division of Preventive Medicine at the Brigham and Women's Hospital, Professor of Medicine at the HMS and Co Principal investigator (Co-Principal Investigator) of the Women's Health Study ONHS). Julie Buring, ScD, is the Deputy Director of the Division, Professor of Ambulatory Care and Prevention at the HMS and Principal Investigator of the WHS. They have trained numerous investigators in the fields of diet, lifestyle and chronic diseases, areas in which they have published extensively. Research: We plan to conduct a prospective analysis within the WHS, an ongoing clinical trial of vitamin E and low-dose aspirin in the primary prevention of cancer and cardiovascular disease among 39,876 women. We will test 4 dietary hypotheses that moderate alcohol intake increases risk of breast cancer, whereas high intake of folate and fiber reduces risk; and caffeine intake is not associated with risk. We will link fiber intake to plasma endogenous sex steroid hormones in a subsample of the WHS. We will also test 4 hormone replacement therapy (HRT) hypotheses that tong-term use of estrogen plus progestin increases risk of breast cancer more than estrogen alone; estrogen plus cyclic progestin increases risk more than estrogen plus continuous progestin; low-dose estrogens confer lower risk than highdose; and use of estrogen is more strongly associated with risk among women drinking alcohol. The ongoing WHS will provide updated and repeated measures of HRT, comprehensive dietary assessment at baseline, and important covariates for breast cancer in addition to follow-up of the cohort and documentation of breast cancer cases (expected N = 1550). The findings from this project could have direct clinical application for efforts to reduce risk of breast cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EFFECT OF ANDROGEN REPLACEMENT ON FAT METABOLISM Principal Investigator & Institution: Jensen, Michael D.; Professor of Medicine; Mayo Clinic Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2001; Project Start 01-JUN-2001; Project End 31-MAY-2002 Summary: Aging is associated with increased body fatness, particularly in the trunk. This change in body fat and body fat distribution correlates with insulin resistance, hypertension, dyslipidemia and diabetes mellitus. Reduced levels of circulating androgens in aging men are associated with insulin resistance and centralization of body fat, whereas reduced levels of DHEA are associated with an upper body fat distribution in both aging men and women. If physiologic replacement of reduced levels of testosterone (men) or DHEA (men and women) can reverse some of the aging related changes in body fat distribution and fatty acid metabolism, this could provide a means of improving health as the United States population continues to age. The present experiments will assess whether reversing the age-related decline in androgens and DHEA can have positive effects on body fat distribution and fatty acid metabolism in the elderly. To accomplish these goals, the proposed experiments will address the following specific aims: 1) to determine whether the changes in body fat experiments will address the following specific aims: 1) to determine whether the changes in body fat experiments will address the following specific aims: 1) to determine whether the changes in body fat distribution which occur with aging are associated with differences in systemic FFA availability, fatty acid oxidation, and regional adipose tissue meal fatty

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acid uptake; 2) to determine whether the change in fat distribution expected to occur with testosterone replacement therapy is associated with improvements in FFA metabolism, increased fatty acid oxidation, or changes in adipose tissue meal fatty acid uptake; 3) to determine whether DHEA replacement therapy in the elderly is associated with decreased body fat and upper-body fat and, if so, to assess DHEA's effects on FFA metabolism, fatty acid oxidation and regional adipose tissue meal fatty acid uptake. In order to address these specific aims we will use state-of-the-art body composition techniques, measures of adipose FFA release, assessments of fatty acid oxidation at rest, following meal consumption, and during exercise. In addition, we will apply a relatively new technique of determining regional adipose tissue meal fatty acid uptake to father information about potential mechanisms of fat redistribution. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EFFECTS OF DIHYDROEPIANDROSTERONE ON BRAIN INJURY Principal Investigator & Institution: Hoffman, Stuart W.; Emergency Medicine; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2001; Project Start 01-APR-2001; Project End 31-MAR-2003 Summary: (provided by applicant): At present, there is no effective pharmacological agent to enhance neurobehavioral recovery after traumatic brain injury (TBI). The longterm objective of this research is to develop a safe and effective treatment that would enhance neurorehabilitation after traumatic injuries to the central nervous system. After the initial cascade of destructive events occurs, the brain is in a state of dysfunction due to injured neurons, disrupted synapses, continuing inflammatory responses, and decreased neuronal activity. However, the brain has the capability to recover significantly from this post-injury state, if proper behavioral or pharmacological therapies are administered. In this proposal, it is the investigators'goal to demonstrate that dihydroepiandrosterone (DHEA) will significantly increase recovery of function. DHEA is a special type of steroid hormone that is synthesized both inside and outside of the nervous system in both males and females. DHEA, a known neurosteroid, can stimulate the formation of new synapses, modulate the immune system, and increase neuronal activity involved in cognitive function. These same characteristics make DHEA worth considering as potential therapy to facilitate recovery of cognitive function after brain injury. In addition, long-term administration of DHEA has shown that it produces no adverse side-effects in rodents or humans. In this proposal, the investigators will investigate whether DHEA can promote a more complete recovery of function after experimental TBI. The investigators will use a controlled cortical impactor to create bilateral medial frontal contusions in rats to model TBI. The investigators goals will be to: (1) determine whether DHEA can promote functional recovery in both males and females, a subject that has received virtually no attention in the experimental literature; (2) determine the most effective dose of DHEA; (3) determine whether treatment with DHEA can affect the morphology and survival of neurons as well as the proliferation of glial cells; and (4) determine if the effects of DHEA on recovery of function can produce a dose dependent causal effect on histological measures. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ENDOCRINE CHANGES AND TREATMENT OF CONDUCT PROBLEMS Principal Investigator & Institution: Dorn, Lorah D.; Associate Professor of Nursing & Psychia; Health Promotion & Development; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260

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Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 31-AUG-2003 Summary: Antisocial behavior in youth is a growing problem in our society. Childhood antisocial behaviors (e.g., conduct problems) can become chronic as reflected in delinquency, adult interpersonal and domestic violence and other criminal behavior. A pattern of chronic child, adolescent and adult antisocial behavior weighs heavily on society with respect to the high cost of treatment, pain and suffering for the victims and their family, and even loss of lives. The majority of studies of antisocial behavior have focused on individual psychological factors, or peer and neighborhood influence. Few studies considered physiological aspects of antisocial behavior in children, in spite of the growing evidence linking physiological processes and crime in adults. The aims of the study are: (1) To examine the relationship between gonadal and adrenal hormone concentrations and conduct problems in children, (2) To examine whether gonadal and adrenal hormones moderate the effect of treatment on conduct problems, and (3) To examine whether treatment of conduct problems alters gonadal and adrenal hormones of children with conduct problems. In response to the NINR RFA, "Clinical Trials: Collaborations for Nursing Research," encouraging a link with an existing clinical trial, we will take advantage of a unique opportunity to assess the effect of a behavior intervention on hormone concentrations in a treatment trial to reduce severe conduct problems in sample of 6 to 11-year-old boys and girls (N = 158). There is random assignment to treatment conducted in either the experimental (EXP) community setting (home, school, neighborhood) or the clinic (CLIN). Services are provided by trained clinicians who administer specialized treatment protocols that address problems across participants (child, parent, teachers) and contexts (home, community). A comparison group for treatment as usual (TAU) in a community mental health center also will be included. Our proposed methodology of adding hormones enhances the field by addressing limitations of the few previous studies of children and conduct problems utilizing physiological measures. We anticipate that findings will contribute to further understanding of the neurophysiology of conduct problems in youth. The project is unique in that it is longitudinal and it examines for the first time, the effect of behavioral interventions on physiological processes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ENDOMETRIAL CANCER AND POSTMENOPAUSAL HORMONE THERAPY Principal Investigator & Institution: Weiss, Noel S.; Professor; Fred Hutchinson Cancer Research Center Box 19024, 1100 Fairview Ave N Seattle, Wa 98109 Timing: Fiscal Year 2001; Project Start 01-MAR-1998; Project End 31-DEC-2002 Summary: The increased risk of endometrial cancer associated with the use of postmenopausal estrogen therapy can be diminished by the concomitant use of progestogen on a cyclic basis. Nevertheless, it is quite uncertain whether the entirety of the increased risk is eliminated, especially in long-term users of cyclic estrogen/progestogen regimens. Additionally, the impact on endometrial cancer incidence of a now-common way of taking hormones, on a combined-continuous basis, has never been evaluated. To address these questions, a population-based case-control study of endometrial cancer is proposed for women 50-60 years of age who reside in three counties of western Washington. An attempt will be made to interview eligible cases diagnosed during 1997-1999 regarding the use of hormonal medications and other exposures and characteristics that bear on the incidence of endometrial cancer. As a basis of comparison for the cases who are 50-64 years of age, interviews will be sough with 50-64 year-old female residents of these counties identified through random digit

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dialing. Controls 65-69 years of age will be identified through the records of the Health Care Financing Administration, and they will be interviewed as well. Potential controls who have previously had a hysterectomy will be excluded. We anticipate obtaining interviews with approximately 300 cases and an equal number of controls. Exogenous hormones offer postmenopausal women substantial benefits with regard to their cardiovascular and skeletal systems. The proposed study has the potential to obtain information that can guide their choice of hormonal regimen so as to minimize the likelihood of endometrial cancer as an adverse effect of this otherwise useful therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ENDOMETRIOSIS :TRADITIONAL MEDICINE VS HORMONE THERAPY Principal Investigator & Institution: Hammerschlag, Richard; Research Director; None; Oregon College of Oriental Medicine 10525 Se Cherry Blossom Dr Portland, or 97216 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-AUG-2003 Summary: (APPLICANT'S ABSTRACT): Endometriosis is a significant public health problem affecting 10-15% of women of childbearing age, many of whom suffer persistent pelvic pain and infertility. Therapeutic options include surgery and hormone therapy that are often temporarily effective but produce unwanted side-effects. The present proposal, based on case series reports of the effectiveness of Traditional Chinese Medicine (TCM: acupuncture and Chinese herbs) for this condition, aims to evaluate whether TCM is as effective as hormone therapy for alleviating endometriosis-related chronic pain. The study is designed as a prospective trial of 66 women, with laparoscopy-diagnosed endometriosis, randomized to TCM or hormone therapy. Women assigned to TCM will be divided into four sub-groups on the basis of the diagnostic categories of endometriosis recognized by TCM. A pre-established acupuncture protocol and herbal formula specific for each sub-group will be followed. This aspect of the research design permits an important feature of the clinical practice of TCM (matching treatment to sub-group diagnosis) to be adopted in a clinical trial. Women assigned to hormone therapy will be treated with the gonadotropin releasing hormone agonist (GnRHa), nafarelin, chosen for this study on the basis of its clinical trial-established efficacy, ease of patient usage via intranasal spray and milder sideeffect profile relative to other GnRHa's. Pelvic pain symptoms (patient-scored) and signs (physician-scored) will be assessed at baseline, after 12 weeks of treatment, and at 12and 24-week post-treatment follow-up. Pelvic examination scores will be determined by a physician blinded to the treatment group assignments. Side effects, including those of pseudomenopause known to result from GnRHa therapy, will be recorded in both groups at 4-week intervals during the 12-week treatment, and at each follow-up time. A further objective is to make a preliminary assessment of whether diagnostic sub-groups of endometriosis recognized by TCM serve as predictors of differential response to hormone therapy. Data obtained from this study, on treatment effectiveness, side effect profiles, recurrence of symptoms, compliance with therapy and drop-out rates, will be used to design a large-scale clinical trial. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ESTROGEN AND EXERCISE--VASCULAR BENEFITS AFTER MENOPAUSE Principal Investigator & Institution: Brownley, Kimberly A.; Psychiatry; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, Nc 27599

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Timing: Fiscal Year 2001; Project Start 15-SEP-2000; Project End 31-AUG-2005 Summary: (Adapted from the applicant's abstract) This application describes a 5-year career development training program for Dr. Kim Brownley. The program includes extensive research and pedagogical training designed to facilitate her growth as an independent researcher investigating combination modality therapies in high-risk cardiac patient populations. The plan is structured around a randomized placebocontrolled study of raloxifene and aerobic exercise training in hypertensive postmenopausal women. Dr. Kathleen Light, whose expertise is in cardiovascular stress responses, hypertension, and hormone (estrogen) replacement therapy (HRT), will serve as mentor. A collaborative support team is also in place, including: 1) Dr. James Blumenthal, who specializes in exercise training interventions in coronary heart disease (CHD); and 2) Alan Hinderliter, M.D. (Cardiology consultant), who will provide training in ultrasound measurement of cardiovascular function, and oversee data interpretation from a clinical perspective. The proposed study will investigate cardiovascular, neuroendocrine, and metabolic functioning in borderline and stage I hypertensive postmenopausal women. This patient group is at increased CHD risk due to elevations in blood pressure (BP), insulin resistance, and low-density lipoproteins. HRT and exercise training can offset these harmful effects by enhancing vasodilatory processes, and their effects may be additive when combined. HRT improves cardiovascular and neuroendocrine function; yet despite these benefits, HRT use and compliance are low because of added cancer risks in some women. Raloxifene, a secondgeneration nonsteroidal selective anti-estrogen, has beneficial lipid and osteogenic effects but does not confer added cancer risks. However, the cardiovascular effects of raloxifene are unspecified. Also, HRT has only modest BP-reducing effects and is thus insufficient antihypertensive therapy for hypertensive postmenopausal women. In contrast, exercise training has robust BP-reducing potential, especially in hypertensive individuals. Therefore, after all subjects complete a 3-month intervention with raloxifene alone, they will be randomized to either an additional 3-month treatment with raloxifene alone or treatment with raloxifene plus exercise training. Pre- and posttreatment assessments will include: 1) impedance cardiography measures of hemodynamic responses to laboratory challenge, 2) 24-hour ambulatory BP and impedance cardiography monitoring, 3) echocardiography assessment of left-ventricular geometry and function, 4) B-mode ultrasound assessment of flow-mediated brachial artery dilatation, 5) assay of neuroendocrine and lipid levels at rest and in response to laboratory stress, and 6) euglycemic insulin clamp to assess insulin sensitivity. Implementation of this training will provide a unique and highly advantageous opportunity for Dr. Brownley to work with this team of senior scientist- practitioners within the collaborative environments of the University of North Carolina and Duke University. This investigation, coupled with the didactic experiences outlined in this plan, will lay the foundation for her future endeavors as a scientific advocate for the systematic investigation of underlying mechanisms of hypertensive heart disease, and for the delivery of effective combination behavioral and pharmacological interventions for stress- related cardiovascular disorders in patients at increased risk for CHD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ESTROGEN RECEPTOR VARIANCE AND CHD RISK IN HERS Principal Investigator & Institution: Herrington, David M.; Professor; Internal Medicine; Wake Forest University Health Sciences Winston-Salem, Nc 27157 Timing: Fiscal Year 2002; Project Start 27-SEP-2002; Project End 31-MAY-2005

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Summary: (provided by applicant): Estrogen raises HDL cholesterol levels - an effect that may account for the favorable association between hormone replacement therapy (HRT) and coronary heart disease (CHD) risk in postmenopausal women. Several lines of evidence suggest that genetic factors also influence HDL levels, although the precise genes involved have not yet been determined. Recent evidence from the Estrogen Replacement and Atherosclerosis (ERA) trial (N = 309) indicates that certain allelic variants in the estrogen receptor-alpha (ER-alpha) gene are associated with more than a twofold increase in estrogen's effects on HDL cholesterol. Women with the favorable genotype (ca. 20% of women) experienced a 26% increase in HDL with HRT compared with a 13% increase observed in the remaining women. However, this trial was too small to determine if these effects translate into an angiographic or clinical benefit. The Heart and Estrogen Replacement Study (HERS) was a large (N = 2763) randomized clinical endpoint trial of HRT for secondary prevention of CHD. This clinical trial cohort provides an ideal opportunity to confirm or refute the associations and interactions observed in the ERA trial with respect to lipids, and extend these observations to other estrogen-sensitive intermediate endpoints and clinical disease outcomes. Therefore, we propose to genotype HERS women with respect to several ER-alpha polymorphisms, and to examine the relationship between these ER-alpha genotypes, HRT use, change in HDL, and risk for CHD events. We will also examine the effects of ER-alpha polymorphisms on other plasma lipids, C-reactive protein, bone mineral density, risk for venous thromboembolic events, stroke, fractures, and all-cause mortality. Use of data and specimens from HERS is an efficient means to study the clinical impact of ER-alpha polymorphisms and possible modulation of estrogen action. If there are common polymorphisms in the ER-alpha gene that modify estrogen's effects on HDL and possibly other domains of estrogen action, this information could improve patients' and clinicians' ability to assess risks and benefits of HRT use. In addition, this information could lead to fundamentally important new knowledge about mechanisms of estrogen action, regulation of HDL cholesterol, and pathogenesis of CHD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ESTROGEN, CYTOKINES AND HEART FAILURE IN WOMEN Principal Investigator & Institution: Reis, Steven E.; Medicine; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 10-DEC-2001; Project End 30-NOV-2006 Summary: (provided by applicant): Congestive heart failure (CHF) is a leading cause of morbidity, mortality, and hospitalization in women. The observation that women with nonischemic cardiomyopathy have an age-related increase in mortality suggests that postmenopausal estrogen loss may alter the phenotypic expression of CHF. Because estrogen is a potent in vitro inhibitor of pro-inflammatory cytokines (e.g., TNFa, IL-1B, IL-6), which are re-expressed by the failing myocardium in patients with CHF and are related to an adverse prognosis, we postulate that estrogen replacement will improve the outcome of postmenopausal women with CHF. This hypothesis is supported by our preliminary data that demonstrate 1) female sex confers a survival advantage in transgenic mice with CHF due to over-expression of TNFa, 2) female sex is associated with an attenuated pathologic response of cardiac myocytes to TNFa, 3) estrogen and progesterone inhibit TNFa production by rat cardiac myocytes, 4) estrogen replacement therapy in postmenopausal women with CHF abrogates an age-related increase in TNFa, and 5) estrogen therapy in women with severe CHF is associated with a significant decrease in mortality. Our proposed randomized placebo-controlled doubleblind study of hormone replacement therapy in women with CHF will evaluate the

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hypothesis that estrogen has a protective effect in postmenopausal women with CHF related to modulation of TNFa and associated "downstream" cytokines (i.e., IL-lB. IL-6) and/or myocardial expression of cytokine receptors. We plan to compare the effects of hormones on functional capacity, biventricular mass and function, and quality of life with their effects on circulating cytokines in postmenopausal women with CHF. To determine the degree of hormone-induced cytokine suppression that is associated with favorable outcome, we will compare post-treatment cytokine levels in women with CHF with cytokine levels in a "control" group of women from the NHLBI WISE study who have no evidence of CHF and normal ventricular function. The results of this study will define the mechanism of estrogen's beneficial effect in postmenopausal women with CHF. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ESTROGEN, VITAMIN E, AND COGNITIVE CHANGE IN WOMEN Principal Investigator & Institution: Dunn, Julie E.; Research Scientist; New England Research Institutes, Inc. 9 Galen St Watertown, Ma 02472 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-AUG-2006 Summary: (provided by applicant): Primary Aims of this study will determine: 1. Effects of vitamin E supplement use (VitE) on cognitive function (CF) and 3-year change in cognitive function in women age 60 and over. Hypotheses: a) Vit E supplement users will have higher scores at baseline and less decline over 3 years on visual memory tests, compared to non-users. 2. Effects of estrogen replacement therapy (ERT) on CF measures over 3 years in women age 60 and over. Hypotheses: ERT users will have higher scores at baseline and three years on verbal memory tests than non-users. Secondary Aims will determine: 1. Effects of plasma alpha-tocopherol (a-tc) levels on CF over 3 years. Hypothesis: a-tc levels will be directly related to visual memory scores at 0 and 3 years. 2. Effects of Apolipoprotein E (ApoE) genotype on change in CF over 3 years and upon VitE and/or ERT effects: Hypotheses: a) test scores will be more likely to decline in women with one or more E4 alleles. b) associations of VitE and/or ERT with CF test scores(Aims 1 &2 above) may differ between those with and without ApoE in those with ApoE e4. Background: Cognitive loss in later life is associated with increased mortality and disability, and reduced quality of life, and may represent an early stage of dementia, possibly amenable to treatment. VitE and ERT are under study as possible means to prevent or delay progression of Alzheimer's disease (AD) and both are biologically plausible as neuroprotective agents. Less is known of their ability to preserve CF in non-demented individuals. Equivocal results of previous studies may be due to nonuniform methodology and use of non-specific or less sensitive CF tests. Methods: 575 women age 60+ will be recruited from Women's Health Initiative (WHI) Observational Study and Diet Modification Control enrollees. ERT history and vitamin supplement and medication data, already collected for WHI, will be updated. Blood samples will be collected for plasma VitE measurement and ApoE genotyping. CF will be assessed with a battery of neuropsychological tests performed on 2 occasions, 3 years apart. Tests will include measures of memory, language, visual-perceptual ability and attention, as well as assessments of functional ability and depressive symptoms. Primary analyses will specifically include tests of verbal memory, which may be more sensitive to ERT effects, and visual memory, which may be most sensitive to effects of age. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: FEMALE SEXUALITY: MODULATION BY ESTROGEN AND ANDROGEN Principal Investigator & Institution: Wallen, Kim; Dobbs Professor of Psychology and Behavi; Psychology; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2006 Summary: (provided by applicant): The hypothesis is investigated that female sexual interest is stimulated by the neural actions of ovarian estrogens and that androgens regulate the bioavailability of these estrogens through interactions with sex hormone binding globulin (SHBG). Three projects, using a rhesus monkey model of endocrine function and behavior, investigate the hormonal basis of female sexual initiation. Project I investigates sexual initiation in females across the menstrual cycle, comparing the occurrence of female sexual initiation in a social group context during normal cycles treated with an androgen receptor blocker (flutamide) or an estrogen receptor blocker (tamoxifen). This will clarify whether androgens or estrogens act neurally to modulate female sexual motivation. Project II tests the novel hypothesis that SHBG regulates bioavailable estrogens and androgens through these steroids' different affinities for SHBG. This project uses a monkey model of hormonal replacement therapy for reproductively prime females after surgical removal of their ovaries and tests the hypothesis that chronic estradiol (E2) ceases to effectively stimulate female sexual interest as estrogen is sequestered by SHBG. It further investigates whether an androgen, 5a-dihydrotestosterone (DHT), with a markedly higher affinity for SHBG than estradiol can acutely and rapidly reinstate female sexual interest by increasing free estradiol by displacing SHBG-bound estradiol. Ovariectomized females receiving chronic estradiol treatment mimicking mid-follicular estradiol levels will be observed for sexual initiation during chronic E2 treatment alone and following chronic E2 and an injection of DHT or E2. Concurrent administration of flutamide or tamoxifen with the estrogen or DHT will discriminate between behavioral changes resulting from the activation of neural androgen or estrogen receptors. The effects of these treatments on neuroendocrine function will also be investigated. Project III investigates whether common human hormonal replacement therapies of chronic estrogen, or chronic estrogen plus testosterone with or without concurrent progestin, can reinstate female sexual interest in reproductively prime ovariectomized female monkeys. The hypothesis will be tested that chronic progestin therapy reduces or eliminates the effectiveness of therapies that reinstate female sexual interest without progestin. These therapies will also be compared on their effects on neuroendocrine function. These studies will markedly increase our understanding of the role that ovarian steroids play in modulating women's sexuality. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: FETAL PANCREATIC DEVELOPMENT & INSULIN SECRETION Principal Investigator & Institution: Hay, William W.; Professor; Medicine; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007 Summary: (Provided By Applicant)The goal of this research project is to understand mechanisms regulating pancreatic development and function that are influenced by nutrients and secondary endocrine factors that augment the effects of nutrients and to focus specifically on the limited pancreatic growth and function in fetuses with intrauterine growth restriction (IUGR). We will test the hypothesis that reduced fetal nutrition from placental insufficiency will result in primary nutrient (glucose) and

22

Hormone Therapy

secondary hormonal (insulin, IGFs) deficiencies that lead to abnormal pancreatic endocrine development and function with 3 specific aims. 1. Analyze pancreatic development and function to define critical developmental periods and identify the adaptations imposed by decreased nutrient availability in the IUGR fetus. 2. Determine the effects of nutrient and hormonal deficiencies on insulin production and secretion in pancreatic endocrine cells in the IUGR fetus. 3. Test the ability to restore normal pancreatic development and function by in vivo nutrient and hormonal supplementation during critical periods of development in the IUGR fetus. The proposed studies will be conducted in our ovine model of IUGR produced by maternal exposure to a moderately hyperthermic environment during gestation. These fetuses develop hypoglycemia and hypoaminoacidemia and secondary deficiencies in insulin and GF concentrations in the latter third of gestation. in vivo and in vitro studies will characterize pancreatic development and function and determine mechanisms responsible for pancreatic abnormalities that are direct consequences of fetal nutrient deprivation. The studies also will provide insight into requirements for clinical interventions to ameliorate pancreatic insufficiency in IUGR fetuses and neonates, hopefully to reduce fetal and neonatal morbidity and mortality, and potentially to reduce the incidence of adult onset diseases that have been associated with low birth weight. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FT-IR OSTEOPOROSIS

MICROSCOPY

OF

MINERAL

STRUCTURE

IN

Principal Investigator & Institution: Boskey, Adele L.; Starr Chair in Mineralized Tissues; Hospital for Special Surgery 535 E 70Th St New York, Ny 10021 Timing: Fiscal Year 2001; Project Start 01-JAN-1993; Project End 31-JUL-2005 Summary: (provided by applicant): Osteoporosis is estimated to affect 15-20 million people (both women and men) each year, causing significant morbidity and mortality. The widely used predictors of fracture risk are bone mineral density (BMD) and incidence of a previous fracture. One of the dilemmas in the management of osteoporosis is that two individuals with the same bone density and similar life-styles can show extensive diversity in their tendency to fracture. There is little information on what, other than differences in life style and fall severity, can account for this discrepancy. The underlying hypothesis of this grant is that discrete differences in mineral and matrix properties contribute to the altered fracture risk in these individuals. Over the past two funding periods, we have shown that Fourier transform infrared microspectroscopy (FTIRM) and imaging (FTIRI) provide reproducible and valuable information on the mineral and matrix properties of bone. We now wish to extend this approach to two new research questions: Aim 1) Do the mineral and matrix properties differ in biopsies from patients with fracture compared with patients without fractures while controlling for age, gender, bone mineral density, and architecture? This question will be tested by assessing biopsied specimens from individuals with different fracture histories and with known age, gender, and bone mineral density. MicroCT will be used to assess architecture of the specimens, and FTIR will be used to characterize mineral and matrix properties. Under this specific aim, we will also examine associations between FTIR parameters and nanoindentation in a subset of biopsies to establish the nanoindentation technique and to test for significant correlations between mineral/matrix properties and indentation modulus and hardness. We will also develop the use of imaging ATR to establish an IR approach that does not required thin sections of embedded bone. Aim 2) Do therapeutic agents reverse the observed

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alterations in mineral and matrix properties? Specifically we shall examine the relative effects of a SERM (selective estrogen receptor modulator), raloxifene, Hormone Replacement Therapy, and a bisphosphonate (Risedronate) on the mineral and matrix properties in pre- and post- therapy biopsies, to identify the agent(s) that reverse(s) the observed alterations in mineral and matrix properties. Emphasis will be placed on those properties identified in Aim 1 that are most predictive of fracture. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENES AND THE ESTROGEN EFFECT ON ENDOMETRIAL CANCER Principal Investigator & Institution: Ross, Ronald K.; Professor; Preventive Medicine; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033 Timing: Fiscal Year 2002; Project Start 01-MAR-2002; Project End 31-DEC-2006 Summary: (provided by applicant): The etiology of endometrial cancer is relatively well understood. Estrogen stimulation of the endometrium without the modulatory effects of progestins is the major cause. Estrogen replacement therapy (ERT) in menopause and obesity are the principal risk factors. The effect of the latter is probably due to the association between postmenopausal obesity and circulating bioavailable estrogen levels. Oral contraceptives and pregnancy, both of which deliver estrogen stimulation to the endometrium but with the continuous modulatory influence of progestins, are associated with reduction in risk. Combination hormone replacement therapy in which a progestin is added to estrogen for all or part of the monthly cycle results in no increase in endometrial cancer risk over that of a non-user of hormone replacement. Despite the fact that ERT and obesity are the major risk factors, only a small proportion of women using ERT or even with extreme obesity will develop endometrial cancer. It would be important from a public health as well as from a mechanistic view to be able to predict which women those will be. We propose to evaluate a series of eight candidate genes (CYP17, CYP19, HSD17B1, ER, CYP1A1, CYP1B1, COMT andPR) in the estrogen biosynthesis, transactivation and metabolism pathways to determine if the effects of these risk factors might be mediated or modified by genetic variability. We will evaluate this question in the context of a prospective epidemiologic study of 133,000 female California teachers (the California Teachers Study) using a nested case-control design. We will also examine in detail the possible impact of phytoestrogens on endometrial cancer risk reduction in conjunction with HRT, obesity and the eight candidate genes under evaluation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GLUCOCORTICOIDS & VITAMIN D: ROLE IN ANTI-TUMOR EFFECTS Principal Investigator & Institution: Johnson, Candace S.; Professor of Pharmaceutical Sciences; Pharmacology; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2001; Project Start 01-FEB-2000; Project End 31-JAN-2004 Summary: Studies in our laboratory demonstrate that vitamin D or 1,25dihy6droxycholecalciferol (calcitriol) has significant anti proliferative activity in vivo and in vitro. Calcitriol induces G0/G1 arrest, modulates expression of p27/p21, induces PARP cleavage, increases the bax/bcl-2 ratio and enhances the anti-tumor activity of cisplatin, carboplatin and paclitaxel. Dexamethasone (dex) potentiates calcitriolmediated anti- tumor activity and vitamin D receptor (VDR) ligand binding in vitro and

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Hormone Therapy

in vivo whereas equivalent doses of methylpredinsolone (mp) do not. Both dex and mp enhance VDR protein expression; however, calcitriol plus dex results in an increase in retinoid X receptor (RXR) alpha levels and calcitriol/mp decreases RXRalpha. Calcitriol/dex suppresses activity mitogen-activated protein kinase ( MAPK) activity while calcitriol/mp have no effect. In a phase II clinical trial of hormone refractory prostate cancer with oral calcitriol and dex, we observed a 50% reduction in prostate specific antigen (PSA) in 31% of patients with no hypercalcemia and a modulation of VDR from peripheral blood monocytes. We propose to determine the mechanisms of calcitriol and dex/mp interaction by the following specific aims: 1) To determine the mechanisms involved in glucocorticoid effects on tumor cells by examining: a) the role of steroid binding to the glucocorticoid receptor (GR); b) the differential role of RXR; and c) whether glucocorticoid effects require calcitriol binding to the VDR, modulate binding to the VDRE, and/or tumor model systems by determining: a) the effect on receptor (VDR/GR) and non-receptor (MAPK) mediated activities, and b) the role of RXR; and 3) To evaluate oral calcitriol and dex in hormone refractory prostate cancer through conduct of a phase I trial to determine: a) the maximum tolerated dose (MTD), toxicities and calcitriol pharmacokinetics, b) the clinical and PSA response, and 4) modulation of peripheral blood monocyte VDR, RXR and MAPK activity by calcitriol and calcitriol/dex. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GONADAL HORMONES ON BODY COMPOSITION, HIV AND DRUG USE Principal Investigator & Institution: Dobs, Adrian S.; Professor of Medicine and Oncology; Medicine; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2001; Project Start 25-DEC-1999; Project End 30-NOV-2002 Summary: Metabolic and endocrine abnormalities are well-described in HIV- infected men and women. Several findings indicate a possible influence of sex hormone levels on AIDS progression. These include 1) the relationship of deceased serum sex hormone levels to HIV-associated wasting, 2) the possible benefits of testosterone replacement therapy on body composition, 3) the recent observation that men and women have varying levels of HIV- viral loads. The mechanisms of sex hormone deficiency in HIVinfected men and women may relate to the combined effects of chronic illness, undernutrition and a complex regimen of medications. Injection drug users (IDU), with or without co- existing HIV infection, may be susceptible to similar metabolic abnormalities, however little is known of the hormonal milieu of this cohort in which an estimated 50 percent of new HIV infections occur. Improved understanding of the overall health status of the IDU may enhance the effectiveness of the relative cures already available to the IDU and subsequently increase control of the AIDS epidemic in this cohort. We hypothesize that male and female IDU are predisposed to endocrine abnormalities, such as hypogonadism, which leads to reductions in lean body mass and quality of life (QOL), and that treatment of male hypogonadism with testosterone improves these parameters. Our overall goal is to understand the effects of IDU and HIV on the hormonal milieu. In a population of men and women, stratified by IDU and HIV status, our specific aims are: 1) To document gonadal function, 2) To determine the relationship of sex steroids to body composition, 3) To ascertain a prevalence estimate of the lipodystropy/metabolic syndrome (as defined in the grant), and 4) To evaluate the safety and efficacy of testosterone replacement therapy on QOL and body composition in men, stratified by HIV status, who have agreed to accept methadone treatment. We propose two clinical experiments: Study A is a cross-sectional study of heroin and/or

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cocaine dependent men and women, stratified by HIV status to evaluate their hormonal milieu and body composition. Study B is a randomized, placebo-controlled, clinical trial in which men with low serum testosterone levels on chronic methadone will be treated with active or placebo testosterone. Our outcome measures are serum hormones, body composition, muscle strength, and QOL. In summary, we intend to characterize the effects of HIV and IDU on the metabolic/endocrine system in men and women and to perform a clinical trial using testosterone replacement therapy in men. These studies can provide information to further our understanding of gender differences in disease progression and treatment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GROWTH FACTORS, SLEEP AND COGNITION Principal Investigator & Institution: Schwartz, Robert; Professor; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2001; Project Start 01-DEC-2000; Project End 30-NOV-2001 Summary: This project will examine the effect of five months of treatment with GEREF vs. placebo on the sleep quality and cognitive function of healthy older women not on estrogen replacement therapy. This project is a parallel study to CRC Study #976, which examines GHRH 1-29 effects on healthy older men and healthy older women on estrogen replacement replacement therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GROWTH CARDIOMYOPATHY

HORMONE

FOR

PEDIATRIC

DILATED

Principal Investigator & Institution: Newburger, Jane W.; Associate Cardiologist-InChief; Children's Hospital (Boston) Boston, Ma 021155737 Timing: Fiscal Year 2001; Project Start 01-JUN-1999; Project End 31-MAY-2003 Summary: Idiopathic dilated cardiomyopathy in children is a rare disorder that is usually progressive despite current available therapies. Cardiac transplantation remains the only current prospect for dramatically improving survival in many patients. Recently, growth hormone (GH) therapy has been shown to induce myocyte growth and enhance the efficiency of myocardial energy metabolism. We propose to obtain preliminary data on the efficacy, as well as safety and tolerability, of GH in improving myocardial function in children with dilated cardiomyopathy. Our goals will be pursued in a prospective, single-center, randomized, partially-blinded crossover trial in children with idiopathic dilated cardiomyopathy of at least six months duration. Patients will be randomly assigned to receive initial therapy with either GH (0.3 mg/kg/week divided into daily doses) plus conventional therapy versus conventional therapy alone. After treatment for 6 months, patients will cross over to the opposite treatment regimen for a period of 6 months. Finally, children treated with GH during the second 6 month block will be followed off GH therapy (i.e., on conventional therapy alone) for an additional 6 months. Specific Aim 1 is to assess the absolute changes in outcomes from baseline to 6 months after initiation of GH therapy. The primary outcome variable will be the change in shortening fraction, assessed by echocardiography. Secondary outcome variables will include changes in the following parameters: a) Measures of left ventricular function, assessed using echocardiographic techniques, including change in rate- corrected velocity of fiber shortening, left ventricular mass, mass-volume ratio, left ventricular shape (degree of eccentricity), wall stress, and stress-velocity, index. b) Measures of functional status, including anaerobic

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Hormone Therapy

threshold, assessed by exercise testing, and parent perception of functional status, assessed by score on the parent report of the Child Health Questionnaire. If GH does result in improved myocardial function, Specific Aim 2 will be to assess the effect of duration of such therapy on changes in fractional shortening and on secondary measures of left ventricular function. Similarly, to assess carryover effects, we will analyze the slope with which these parameters deteriorate after discontinuation of GH therapy. This goal will be accomplished by serial measurements of echocardiographic parameters at baseline; at one, three, and six months after institution of GH therapy; and then at one, three, and six months after its discontinuation. Specific Aim 3 will be to describe adverse side effects related to administration of GH in this population of children with idiopathic dilated cardiomyopathy. Adverse effects will be assessed at multiple time points within and after the period of GH administration. We hypothesize that GH therapy will have a very low rate of adverse effects in our study population, based upon its excellent safety profile when used in other pediatric populations with normal levels of endogenous GH. Inferences reached in this study may be broadly applicable to other, secondary forms of dilated cardiomyopathy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GROWTH HORMONE IN CHILDREN WITH SHORT BOWEL SYNDROMEN Principal Investigator & Institution: Duggan, Christopher P.; Children's Hospital (Boston) Boston, Ma 021155737 Timing: Fiscal Year 2001; Project Start 01-DEC-2000; Project End 30-NOV-2001 Summary: This is a multi-center prospective study to evaluate the effects of recombinant growth hormone (GH) on effecting intestinal adaptation in children with short bowel syndrome (SBS). The objectives are to define the effects of 3 months of treatment with growth hormone on body growth and composition and gut tissue and function by fat and carbohydrate absorption studies, small bowel biopsies for histologic examination for expression of IGF-I and II receptor and IGFR, and need for nutrition support, in patients with short bowel syndrome. Additionally, to define the metabolic actions of growth hormone used in conjunctin with total parenteral nutrition and/or enteral nutrition, with specific reference to the following: protein (whole body protein synthesis and proteolysis), carbohydrate (hepatic glucose production and glucose disposal), and fat (lipolysis). Background: Mortality rates among infants with short bowel syndrome have been reduced substantially by the use of parenteral nutrition (PN). Unfortunately, PN is primarily a supportive therapy, since it fails to correct the fundamental defect of SBS: inadequate mucosal surface area. Use of PN has also been associated with significant morbidites, including life-threatening sepsis, thrombotic disorders, inadequate bone mineralization and chronic liver disease. Surgical therapy for SBS has evolved to include small intestine transplantation, but success rates have been modest. A major advance in the field would be the design of new medical therapies to enhance the capacity of the bowel to adapt following extensive resection. Growth hormone has been postulated as an important hormone in intestinal adaptation. GH increases crypt cell proliferation of human duodenal mucosa in vitro and increases body weight, distal ileal weight and mucosal height in rats undergoing extensive small intestine resection. GH recetors have been located in both animal and human gastrointestinal tract tissues. GH potentiates protein anabolism associated with TPN in adult patients and, in conjunction with the amino acid glutamine and a modified diet, has been shown to improve nutrient absorption in adults with SBS. It has been postulated that adults who

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are many years past their intestinal resection might be less susceptible to its benefits than young children. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HISTORY OF HORMONE REPLACEMENT THERAPY, 1960-2000 Principal Investigator & Institution: Watkins, Elizabeth S.; Individual Award--Watkins, Elizabeth Sie 6516 Northumberland St Pittsburgh, Pa 15217 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2006 Summary: (provided by applicant): The goal of this project is to produce the first sociocultural historical study of the changing rationales for prescribing hormone replacement therapy (HRT) for menopausal and post-menopausal women from the 1960s to the present. The resulting book will provide a historical perspective for contemporary debates about the health care and health policy implications of menopause, aging, and HRT. The study is driven by three main questions. 1) How and where do physicians and patients get their information about menopause, aging, and medical treatments? This project investigates the interactions among scientists, physicians, drug companies, government agencies, feminist health activists, the media, and the public in the construction, dissemination, and translation of medical information for midlife and older women. 2) In what ways have the phenomena of menopause and aging been both medicalized and de-medicalized? While menopause and its sequence, like other aspects of women's health (e.g., childbirth, birth control), have increasingly come under medical control in the 20th century, there has also been a parallel trend in recent decades to redefine menopause as a "natural" event. This project will analyze the differences and similarities between these two views and set them in the larger context of health policy making and the American pursuit of health. 3) What is the relationship between the medical treatment of menopause and cultural conceptions of aging? This project locates the use of HRT in the context of changing expectations and changing roles for older women in American society. Using historical methodologies to investigate the variety of actors engaged in disseminating information about menopause, aging, and medical treatment, this study will enrich our understanding of the practices, contexts, and meanings of aging and related health-care issues among American women. The primary product will be a book written for a broad audience, including historians, health policy makers, physicians, nurses, other health care providers, and the general public. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: HIV: GENDER AND SEX HORMONE EFFECTS ON T CELL KINETICS Principal Investigator & Institution: Hellerstein, Marc K.; Professor of Medicine; J. David Gladstone Institutes 365 Vermont St San Francisco, Ca 94103 Timing: Fiscal Year 2001; Project Start 23-APR-2001; Project End 31-MAR-2006 Summary: (Abstract Provided by Applicant) Gender differences have been documented for many aspects of immune function and are likely mediated by the major reproductive hormones (androgens, estrogens and progesterone). Gender differences in the natural history of human immunodeficiency virus-type 1 (HIV-l) infection have also been described. In particular, a different relationship between HIV-1 viral load (VL) and progression of disease has been reported for women as compared to men. The in vivo effects of gender or reproductive hormones on proliferation and survival of T cells, including thymic production of T cells, in the setting of HIV- 1 infection have not been directly tested, however. The objectives of our proposed studies are to compare the

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Hormone Therapy

natural history of T cell turnover in men and women with early HIV-1 disease and to establish the consequences of sex steroids on T cell turnover, including thymopoiesis, in HIV-l infection. These studies are now possible in humans because of the recent development of stable isotope-mass spectrometric techniques for directly measuring the kinetics of purified T cell subpopulations in vivo. Three clinical studies will be performed. Study #1 will compare the natural history of CD4+ and CD8+ T cell kinetics in untreated, CD4-matched men and women with early HIV-l infection (CD4 counts 500-750 cells/uL; n~l5 per group). T cell kinetics will be measured by two complementary techniques ([6,6-2H2] glucose incorporation and die-away curves, to characterize memory/effector-phenotype T cell dynamics; long term 2H2O incorporation, to characterize kinetics of naive-phenotype T cells) at baseline then every 12-18 months over a 3-4 year follow-up. Correlation between VL, CD4 count, thymic mass (by CT scan), excision circles, and blood measurements (cytokines, hormones) will be compared in men and women. Our hypothesis is that chances in T cell kinetics will track with CD4 count in both genders, but at a lower VL in women. Study #2 will compare the effects of puberty in HIV-1 infected pre-adolescent boys and girls (n=8 per group). The outpatient 2H2O approach will be used to measure T cell dynamics. Other parameters will be correlated as in study #1. The central hypothesis is that the rise in sex steroids will suppress thymopoiesis in both genders. perhaps greater affecting boys. Study #3 will compare the effects of reproductive hormone replacement therapy in hypogonadal adult men and women with HIV-1 infection (n=8 per group). The 2H2O method for measuring T cell dynamics will be used. with other measurements as in Studies I and 2. The hypothesis is that sex steroids will reduce production of naivephenotype T cells in both men and women, with perhaps a greater effect in men. In summary, we propose to determine directly, in vivo, whether sex steroids alter T cell kinetics (particularly thymopoiesis) in HIV-1 infected humans. and whether T cell turnover tracks better with CD4 count than VL in women, compared to men. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HORMONE METABOLISM

REPLACEMENT

AND

CEREBRAL

GLUCOSE

Principal Investigator & Institution: Woodard, John; Psychology; Finch Univ of Hlth Sci/Chicago Med Sch North Chicago, Il 60064 Timing: Fiscal Year 2000; Project Start 30-SEP-2000; Project End 31-AUG-2004 Summary: Epidemiological studies have suggested that estrogen replacement therapy (ERT) may reduce the risk of developing Alzheimer?s disease and may slow cognitive decline in demented women. In women without dementia, higher serum estradiol levels have been associated with better memory performance, although there is also evidence that progestins may actually attenuate or reverse many cognitive benefits of estrogens. Neither the mechanisms by which ERT may produce beneficial cognitive effects nor the manner by which progestins could moderate the beneficial effects of estrogen are wellunderstood. Recent scientific interest has been directed toward investigating estrogen?s effects on glucose transport and utilization within the central nervous system (CNS). Given that glucose is the primary energy source of the brain, that impaired glucose transport promotes ATP depletion and compromise of a number of energy-dependent processes (particularly in synapses), and that estrogen exerts widespread cellular and behavioral effects on the CNS, the relationships between estrogen, glucose metabolism, and CNS functioning appear particularly compelling. It is not known whether ERT may produce an increase in global cerebral metabolic rate of glucose utilization (CMRglc) in humans or whether there are specific regional CMRglc increases that may modulate

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enhanced cognitive functioning. In this study, we propose a three-arm, randomized, double blind study of the effects of a 3-month intervention period of conjugated equine estrogen (CEE) alone, CEE plus medroxyprogesterone acetate (MPA), and placebo on modulation of global and regional CMRglc in healthy, cognitively intact postmenopausal women aged 60 to 65 years, inclusive. All participants will undergo pre- and post-intervention dynamic FDG-PET studies of CMRglc. The two intervention groups will include 3 women without and 3 with a uterus, respectively, and the placebo group will contain 3 with a uterus. We will use FDG PET to accomplish the following specific aims: 1) To determine whether ERT produces increases in global and/or regional CMRglc after 3 months by comparing hysterectomized women on ERT versus placebo; 2) To determine whether progestin-estrogen replacement therapy (PERT) produces increases in global and/or regional CMRglc after 3 months by comparing women with a uterus on PERT versus placebo; and 3) To determine whether PERT produces a different pattern or magnitude of global and/or regional CMRglc after 3 months compared to ERT. Secondary specific aims are: 1) To use dynamic PET imaging to ascertain whether either ERT or PERT may promote either glucose transport or phosphorylation by determining kinetic rate constants, and 2) To determine if cortical metabolic changes seen following ERT or PERT correlate with general or specific cognitive changes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HORMONE CARDIOVASCULAR RISK

REPLACEMENT

AND

METABOLIC

Principal Investigator & Institution: Sites, Cynthia K.; Obstetrics and Gynecology; University of Vermont & St Agric College 340 Waterman Building Burlington, Vt 05405 Timing: Fiscal Year 2001; Project Start 02-DEC-1998; Project End 30-NOV-2003 Summary: The menopause transition is associated with a pronounced increase in risk of cardiovascular disease. Hormone replacement therapy in postmenopausal women reduces the risk of cardiovascular disease by approximately 50 percent, although the mechanisms involved are poorly understood. We will examine the impact of hormone replacement therapy on metabolic risk factors affecting cardiovascular disease and future health in aging women. Our overall hypothesis is that hormone replacement therapy in the early postmenopausal period reduces the central accumulation of body fat and improves insulin sensitivity, thereby reducing a metabolic risk factor for cardiovascular disease. A total of 88 women will be recruited for this 2-year randomized double-blinded placebo-controlled longitudinal study. We will measure outcomes of changes in body fat distribution and insulin sensitivity on 4 occasions (baseline, 6 months, 1 year and 2 years) in women taking continuous conjugated estrogens plus medroxyprogesterone acetate or placebo. Our study will provide new information on the temporal sequence of changes in outcome variables. We will use: 1) computerized tomography (CT) and dual photon x- ray absorptiometry (DEXA) scanning to measure intra-abdominal body fat and total body fat, and 2) euglycemic clamps to measure insulin sensitivity. Analysis of these data will provide an understanding of the impact of hormone replacement on the syndrome of central obesity and insulin resistance, which predisposes women to increased risk for cardiovascular disease. In addition, our study may allow physicians to target hormone replacement to women with specific body compositions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: HORMONE REPLACEMENT FOR PREVENTION OF VISCERAL OBESITY Principal Investigator & Institution: Cefalu, William T.; Associate Professor of Medicine; Medicine; University of Vermont & St Agric College 340 Waterman Building Burlington, Vt 05405 Timing: Fiscal Year 2001; Project Start 01-JUL-2000; Project End 31-AUG-2003 Summary: The goal of this study is to determine the therapeutic role of hormone replacement therapy (HRT) to prevent visceral obesity in postmenopausal women. The hypothesis is that HRT will augment the loss of visceral fat in postmenopausal women who undergo a 6-month weight reduction program, and that HRT will be useful in preventing visceral fat regain in women who continue HRT after a one-year follow-up. In addition, the study will examine whether changes in visceral fat are predictive of alterations in insulin sensitivity. postmenopausal women with abdominal obesity will be randomly assigned to either HRT or placebo intervention. All women will participate in a 6-month program of exercise and dietary restriction designed to induce a moderate fat loss. Women will be re-examined after a one-year follow-up period. Total abdominal and visceral fat will be measured with CT, body composition with DXA, insulin sensitivity with an euglycemic/hyperinsulinemic clamp, and energy balance with indirect calorimetry and doubly-labeled water before and after the weight reduction program, and after the one-year follow-up. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: HORMONE REPLACEMENT THERAPY AND ISCHEMIC STROKE SEVERITY Principal Investigator & Institution: Bushnell, Cheryl D.; Associate in Medicine; Medicine; Duke University Durham, Nc 27706 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-AUG-2006 Summary: (provided by applicant): Experimental studies in laboratory animals have shown that estrogen reduces stroke severity, but the impact of hormone replacement therapy (HRT) on ischemic stroke severity in humans is not known. There are 2 broad, longterm objectives of this project. The first objective is to determine whether there are differences in stroke severity and outcome between women who are HRT users and women who are nonHRT users. The second objective is to determine whether any difference in these 2 groups is related to enhanced fibrinolysis. The Specific Aims of this proposal are 1) to compare the initial stroke severity in women who are users and nonusers of HRT, 2) to measure any differences in markers of the coagulation and fibrinolytic systems in the acute stroke period, and 3) to assess stroke outcomes in women based on poststroke use or nonuse of HRTs. Subjects for this prospective, observational study will be women admitted with acute ischemic stroke to an academic medical center. In the acute stroke period, initial stroke severity will be assessed using the NIHSS and markers of coagulation (prothrombin fragment F1,2 and thrombinantithrombin III complex) and fibrinolysis (plasminogen activator inhibitor type I) will be measured. Relevant historical and demographic data will be collected. At 3 months poststroke, neurologic impairment (NIHSS), functional status (Barthel Index and Modified Rankin), and quality of life (Stroke Impact Scale) will be assessed. The differences in initial stroke severity will be analyzed accounting for co-variates, and the 3month outcomes will be adjusted for initial stroke severity. This work will provide critical information for physicians prescribing HRT for women at risk for stroke and address whether it is safe to continue these medications in the sub-acute period after

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stroke. As a K23 proposal, this project will not only provide important clinical information, but is a natural extension of the candidate's previous experience with coagulopathies and stroke, now combined with the commitment to study the impact of stroke in women. This proposal will also provide critical transitional support in a mentored environment leading to the candidate's complete independence as a clinical investigator. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HORMONE REPLACEMENT THERAPY AND LARGE BOWEL CANCER RISK Principal Investigator & Institution: Newcomb, Polly A.; Member and Acting Head; Fred Hutchinson Cancer Research Center Box 19024, 1100 Fairview Ave N Seattle, Wa 98109 Timing: Fiscal Year 2002; Project Start 19-AUG-1998; Project End 31-MAY-2004 Summary: The benefits and risks of estrogen replacement therapy continue to confuse women and their physicians. Recent evidence suggests that estrogen replacement may be associated with reductions in large bowel cancer, a common disease among postmenopausal women. Further study of this potentially important association would provide more precise estimates of the magnitude of effect, identify salient patterns of use, and, importantly, supply insights into the biology of this tumor in women. A population-base case-control study is proposed to evaluate the association between postmenopausal hormones and the occurrence of colorectal cancer. This study will specifically assess use of estrogens with and without progestin, the duration and currency of hormone use, and inter-relationships with body mass. Additional aims of this study are to elucidate the mechanisms of this inverse association, specifically the relationship of HRT to hormone receptors and proliferation in the bowel, and to examine the modifying role of more common cancer susceptibility genes influencing the metabolism of estrogens. Over a three year period, interviews will be conducted with 1,100 women with newly diagnosed cancer of the colon or rectum selected from the population. In addition to the structured telephone interview, fixed diagnostic tissue will be obtained from 540 case in order to evaluate estrogen-receptor status and proliferation markers. Blood samples on a sample of 600 (most with diagnostic tissue) cases and 600 controls will be obtained for genetic studies of polymorphisms relevant to estrogen metabolism and function, specifically CYP17 and the estrogen receptor gene. The proposed study and its extensions should provide clear evidence for the degree to which HRT is protective against colorectal cancer and permit the determination of some of the relevant pathways for that protection. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: HORMONE REPLACEMENT THERAPY WITH PROGESTERONE CREAM Principal Investigator & Institution: Hermsmeyer, Kent R.; Dimera, Llc. 2525 Nw Lovejoy St, Ste 401 Portland, or 97210 Timing: Fiscal Year 2000; Project Start 13-AUG-1998; Project End 31-AUG-2004 Summary: The objective of this project is to further develop a new progesterone formulation that is effective for hormone replacement therapy-protecting the coronary arteries against hyperreactivity. Such hyperreactivity results from the deficiency of progesterone after the cessation of ovarian function after menopause during the normal aging process. The anticipated new product will be further studied in monkeys in the

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catheterization laboratory and in human stress test electrocardiogram and echo cardiology protocols. These studies will determine the effectiveness of progesterone in extending treadmill stress test duration, echocardiographic cardiac wall motion, and lipid biochemical measures of coronary function. We will also explore the possible relationship of changes in blood lipids and platelet function. The new formulation is designed to be accepted sufficiently well by post- menopausal women to encourage compliance among those who initiate hormone replacement therapy-for a duration of decades in many cases. Protection of the cardiovascular system by progesterone can be expected to provide for a significant decrease in the incidence of cardiovascular disease during aging, and improved quality of life in post-menopausal women. The skin cream formulation is well accepted by women, has optimal pharmacokinetics for a once a day treatment, and is hypothesized to reduce cardiovascular risks, including coronary artery disease. Even though the risk of death due to cardiovascular causes is nearly 50% for post-menopausal women, and is far greater than any other risk, the presently available forms of hormone replacement therapy are used by only a fraction of those who would benefit. This leading risk of death and' available measures to minimize that risk are neither well understood nor readily accepted by post-menopausal women. This formulation has the potential to significantly improve that situation and enhance quality of life in post-menopausal women. PROPOSED COMMERCIAL APPLICATIONS: The percutaneous formulation of progesterone will produce a blood level to minimize the risk of cardiovascular disease, and thus may find widespread application in hormone replacement therapy. The number of people who would be potential consumers for the product consists of all postmenopausal women, a rapidly growing number which already exceeds 20 million. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HRT AND EXERCISE EFFECTS ON CENTRAL ARTERIAL COMPLIANCE Principal Investigator & Institution: Moreau, Kerrie L.; Integrative Physiology; University of Colorado at Boulder Boulder, Co 80309 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2007 Summary: (provided by applicant): Candidate. The candidate, Kerrie L. Moreau, Ph.D., is a physiologist currently supported by an individual NRSA from NIA. Dr. Moreau's past and current research focus has been on physical activity, aging, and cardiovascular health, particularly in women. Her immediate goal is to acquire new research and professional skills to help her achieve her long-term goal of developing a successful independent extramurally-funded research program in aging. The proposed KO1 development plan should provide Dr. Moreau with the necessary training to achieve her goal. Career Development Plan. Dr. Moreau's research career development training activities consist of: 1) acquiring new research skills associated with and complimentary to (e.g., micro array gone expression analysis) the proposed research plan; and 2) structured activities including formal course work; attendance and presentation at journal clubs, seminar series, and scientific meetings; and regular interactions with her mentoring team. Environment. The environment for Dr. Moreau's training should be outstanding. The Sponsor and Co-sponsor, Drs. Douglas Seals and Wendy Kohrt, are well- established extramurally-funded scientists with strong records of successful mentoring in biomedical aging research. They are complimented by several consulting mentors who will provide guidance in specific areas of the training plan. Other faculty in aging research enhance the environment. Research. The general aim will be to determine the relative efficacy of 3 commonly used Hormone Replacement Therapy

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(HRT) regimens, regular aerobic exercise, and the combination of HRT and exercise for improving central (carotid) arterial compliance, the associated functional benefits, and the underlying mechanisms in healthy sedentary estrogen-deficient postmenopausal women. The general hypothesis is that HRT and exercise will, independently and additively, improve arterial compliance which will, in turn, result in functional benefits (e.g., improvements in cardiovagal baroreflex sensitivity and left-ventricular function/structure), and that these favorable adaptations will be mediated in part by a decrease in sympathetic tone (HRT only) and/or a reduced oxidative stress-associated improvement in vascular endothelium- dependent vasodilatory tone. Moreover, the amount of improvement with hormone supplementation and the additive effect of exercise will differ among HRT regimens. A 2-phase placebo controlled intervention trial employing state-of- the-art measurements of autonomic (e.g. micro neurography) and cardiovascular (e.g., high-resolution ultrasonography) function will be conducted. The expected results should provide new physiological and clinical information concerning the use of various HRT regimens and exercise for the primary prevention of reduced central arterial compliance with age and estrogen deficiency, the corresponding autonomic and cardiovascular functional benefits, as well as insight into the underlying mechanisms involved. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HYPOPITUITARISM AFTER MODERATE AND SEVERE HEAD INJURY Principal Investigator & Institution: Kelly, Daniel F.; Associate Professor; Harbor-Ucla Research & Educ Inst 1124 W Carson St Torrance, Ca 90502 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007 Summary: (Verbatim from applicant's abstract) Pituitary function is rarely considered in the care of patients with traumatic brain injury (TBI). Yet, TBI poses significant risk to pituitary function given the gland's encasement within the sella, its delicate infundibular-hypothalamic structures and vulnerable vascular supply. Autopsy studies of fatal head injury victims confirm that up to one third sustain pituitary necrosis and hundreds of case reports document chronic post-traumatic pituitary failure. The longterm neurobehavioral problems that plague a majority of TBI victims are quite similar to those of patients with hypopituitarism. It is the primary hypothesis of this study that many TBI victims suffer from unrecognized pituitary dysfunction that acutely and chronically compounds the initial brain injury and limits maximal recovery. The major hypotheses being tested in this study are that i) post-traumatic pituitary failure, both acute and chronic, results primarily from a vascular insult to the pituitary gland and/or its hypothalamic-infundibular connections; ii) in the acute phase of TBI such injury can result in acute secondary adrenal insufficiency, iii) in the chronic phase of TBI such injury can result in long-term hypopituitarism, and iv) treatment of pituitary hormone deficiencies will improve neurobehavioral functioning and quality of life in the chronic post-traumatic state. These hypotheses will be tested in a three-phase study. In the first phase, acutely post-injury, subjects will undergo serial determinations of adrenocortical function to diagnose and treat acute adrenal insufficiency. Patients found to have inappropriately low cortisol levels, will be randomized to placebo or hydrocortisone therapy for 48 hours, and changes in blood pressure and vasopressor requirements will be monitored. Pituitary/hypothalamic MRIs will also be performed at 10 days and 6 months post-injury to assess for acute structural lesions and chronic pituitary volumetric changes. In the second phase, at 2 and 6 months post-injury, pituitary function tests will be performed. Hormone deficient patients will be placed on hormone replacement

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except for growth hormone (GH) after the 2-month time point. In the third phase, from 6 to 12 months post-injury, TBI patients with GH deficiency or GH insufficiency, who have memory impairment, concentration deficits, depression, anxiety or fatigue will be entered into a double-blind placebo-controlled GH replacement therapy trial to assess changes in these neurobehavioral and quality of life complaints. By diagnosing and treating both acute and chronic traumatic neuroendocrine deficiencies, this study may dramatically improve the lone-term prognosis of many TBI patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INTERACTION OF CALORIC RESTRICTION WITH LONGEVITY GENES Principal Investigator & Institution: Bartke, Andrzej; Professor; Physiology; Southern Illinois University Carbondale 900 S. Normal Carbondale, Il 629014709 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-AUG-2006 Summary: (provided by applicant): Our long-term objective is to identify the molecular mechanism(s) responsible for delayed aging and prolonged longevity of animals exposed to caloric restriction (CR). We will approach this goal by examining interactions of CR and longevity assurance genes (LAGs) in a mammalian system. Will help identify the unique, intersecting and additive effects of CR and dwarfism upon aging to provide an inferential basis to determine which candidate and novel mechanisms specifically relate to aging in these models. This experimental design is unique and powerful. The proposed domains of phenotypic analysis combine careful study of standard candidates and exploratory use of microarrays. Hormone therapy is proposed as an experimental manipulation to further test the hypotheses. The concept is promising, but the design requires additional controls (revise and add to budget). The environment, investigators and model background provide high confidence for an informative study. Loss-offunction mutations at the Prop1 and Pit1 loci, as well as targeted disruption of the growth hormone receptor (GHR)/binding protein gene, delay aging and greatly prolong life in the mouse. Phenotypic characteristics of these novel models of delayed aging overlap with many of the well-documented effects of CR. We have recently demonstrated that in one of these models, the Ames dwarf (Prop1df) mouse, CR may extend life beyond the limits achievable with CR or dwarfism alone. We believe that studying interaction of CR with different LAGs is a powerful approach for identifying those changes in gene expression and in physiological characteristics that are consistently associated with prolonged longevity. These changes can be viewed as potential mechanisms and/or biomarkers of delayed aging. In the proposed studies, we will determine whether CR increases life span in Snell dwarf, in GHR knock out (GHRKO) mice, and in Ames dwarf mice given replacement therapy with thyroid hormone. We will also examine ad libitum (AL) fed and CR dwarfs at 2.0, 2.5 and 3.0 years of age to determine whether extension of life span in Ames dwarfs by 30% CR is associated with delay of aging as assessed by tests of cognitive and immune function. To identify mechanisms of CR action in long-lived mice, we will examine the effects of 6 months of CR on gene expression in the liver and muscle, on plasma glucose, insulin, and corticosterone levels, on activity of antioxidant enzymes, and on body temperature in dwarf and GHR-KO, as compared to normal mice. Gene expression will be assessed by microarrays as in our recent studies of the effects of Ames dwarfism on age-related changes in hepatic gene expression, and results of particular interest will be verified by Northern analysis. The results will be used to determine how CR and LAGs interact to delay aging, and to identify putative mechanisms of action of CR at the molecular and organismal levels. In future studies, we will verify involvement of these mechanisms in

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the control of normal and delayed aging and examine their potential in designing interventions that prolong health span. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: LONGITUDINAL CHANGES IN HIP GEOMETRY AND SKELETAL MUSCLE Principal Investigator & Institution: Chen, Zhao; University of Arizona P O Box 3308 Tucson, Az 857223308 Timing: Fiscal Year 2003; Project Start 15-AUG-2003; Project End 30-JUN-2008 Summary: (provided by applicant) This study will be conducted among a large multiethnic cohort (N = 11,432) from the nationwide Women's Health Initiative (WHI), which includes an observational study and three clinic trials. The age range of this cohort is between 50-79 years at the baseline, and it has multiple minority groups: 1583 black, 739 Hispanic and 149 Native American women. The maximal follow-up time of this cohort will be 9 years by 2005. Dual-energy x-ray absorptiometry (DXA) is used to measure bone mineral density (BMD) and body composition. The randomized clinical trials and longitudinal nature of the WHI study provide a unique opportunity to investigate: 1) treatment effects of hormone replacement therapy (HRT) and calcium and vitamin D supplementation on hip structural geometry; 2) longitudinal changes in skeletal muscle mass as a factor in hip fragility; and 3) ethnic differences of mean and rates of changes in hip geometry and muscle mass. Special computer software will be used for analyzing hip scans by dual-energy x-ray absorptiometry (DXA). Crosssectional area, subperiosteal width, estimated endocortical diameter, estimated mean cortical thickness, buckling ratio and section modulus at the femoral neck, at the intertrochanteric and the femoral shaft regions will be assessed. MRI scans will be used as references to calibrate total, appendicular and leg skeletal muscle measurements from DXA subregion analyses. Prevalence rates of sarcopenia (low muscle mass) among each age and ethnic group will be studied. Random Effects Models will be used to analyze the longitudinal data. This proposed study is not funded by the WHI program. Recourses that the WHI will provide include DXA scans, fall and fracture data, and information on covariates. Since the majority of data collection work has been or will be done by the WHI, we will be able to cost effectively test multiple important scientific hypotheses in this study. The novel approaches in this ancillary study will enhance scientific contributions of the WHI program. The significance of the proposed study is that it may demonstrate the utility of bone structural analysis in addition to bone mass measurements for understanding ethnic differences in fracture risk and/or for assessing the effect of pharmacologic therapy (i.e. HRT) on bone health. Furthermore, if the muscle variables are found to be a strong determinant of bone structure in the proximal femur and the risk of fall, then it may be important to develop interventions to increase muscle mass in this region to prevent hip fracture. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: LONG-TERM COMPLICATIONS OF CHILDREN/ADOLESCENTS & CANCER Principal Investigator & Institution: Green, Daniel M.; Associate Chief; Roswell Park Cancer Institute Corp Buffalo, Ny 14263 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2007 Summary: (provided by applicant): We propose to hold a two-day conference on June 28-29, 2002 at Queen's Landing Inn (Niagara-on-the-Lake, Ontario, Canada). The

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program will be of interest to pediatric hematologists/oncologists, pediatric nurse practitioners, pediatric psychologists, pediatric oncology social workers, medical oncologists, fellows, residents, interns, clinical research associates and other primary care providers. The topic of bone complications following treatment of children and adolescents for cancer will be addressed. The goals of the 7th International Conference on Long-Term Complications of Treatment of Children and Adolescents for Cancer will be to: 1) Review the biology of the basic multicellular unit; 2) review the role of the kidney in the regulation of calcium metabolism; 3) review the effect of cis-platinum on renal function and calcium metabolism; 4) review the late effects of ifosfamide on the kidney; 5) review the issues involved in the measurement of bone density; 6) review the effects of radiation therapy effects on bone density; 7) review the effects of glucocorticoid hormones on bone density; 8) review the roles of androgen and estrogen in skeletal physiology; 9) review the issues involved in the management of osteoporosis due to ovarian failure; 10) review the role of growth hormone in the regulation of bone density; and 11) review the issues involved in the duration of treatment with growth hormone replacement therapy. The conference will include presentations by nationally and internationally recognized experts in these areas. The conference will facilitate subsequent discussions among the investigators of the Childhood Cancer Survivor Study, most of whom attend this conference, regarding future research on bone complications among participants in the Childhood Cancer Survivor Study. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MALNUTRITION IN DIALYSIS PATIENTS Principal Investigator & Institution: Ikizler, Talat A.; Medicine; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2001; Project Start 30-SEP-1992; Project End 31-MAR-2003 Summary: Protein-energy malnutrition, a well-established major risk factor for morbidity and mortality, is found in 40% of patients with end-stage-renal disease. Investigators have shown that malnutrition develops before the initiation of dialysis in a large portion of patients, particularly when residual renal function declines to less than 25% of normal. Despite advances in renal replacement therapy, no significant improvement has been observed in the nutritional status of ESRD patients. To overcome this problem, three promising interventions have been highlighted. These include: 1) timely initiation of dialysis; 2) increased dose of hemodialysis; and 3) treatment with anabolic agents. The applicant proposed to investigate these three approaches to improve nutritional status of patients with chronic renal failure (CRF). The applicant will test a hypothesis that using "early" versus "conventional" criteria for initiation of dialysis preserves nutrient homeostasis and subsequent morbidity. Patients with moderate CRF will be randomized to dialysis using either early or conventional criteria for initiation to evaluate how nutritional status, hospitalization rate and death are altered over a two-year period. The applicant will also test the hypothesis that a higher than "adequate" dose of dialysis improves nutritional status in patients with CRF using patients who will be randomized to receive two doses of dialysis over a two-year period. Furthermore, the effect of the administration of recombinant-human- growth hormone on nutritional status will be evaluated in patients with ESRD. These three studies will establish the link between malnutrition and renal failure, and provide the basis for intervention to improve nutritional status. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MANDIBULAR BONE MINERAL DENSITY Principal Investigator & Institution: Lane, Nancy E.; Associate Professor; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 94122 Timing: Fiscal Year 2001; Project Start 01-AUG-1999; Project End 31-JUL-2004 Summary: Adult periodontitis is a chronic inflammatory disease of bacterial etiology that results in alveolar bone loss. It has been reported recently that alveolar bone mass is reduced in women who have adult periodontitis. In addition, individuals with spinal osteoporosis have low mandibular bone mass compared to normal women. Studies in animals and humans have shown that the bisphosphonate, alendronate, can prevent bone loss by inhibiting osteoclast-mediated bone resorption and may also reduce local and systemic levels of inflammatory cytokines and some new bone formation. However, bisphosphonates and other therapies do not return bone mass to normal. However, bisphosphonates and other therapies do not return bone mass to normal. Administration by daily infection of parathyroid hormone (hPTH 1-34) has been found to stimulate new bone formation in patients. The goal of the present study is to restore lost bone in adult patients with severe periodontitis and low mandibular bone mass. The hypothesis underlying this study are: (1) that two years of bisphosphonate administration in conjunction with conventional periodontal therapy will lead to significantly greater new bone formation and gains in clinical attachment and alveolar bone height than conventional therapy alone, and that (2) in patients with bisphosphonate, the addition of hPTH (1-34) treatment, when used in conjunction with conventional periodontal treatment will significantly increase alveolar bone mass and may restore alveolar bone mass toward normal as compared to individuals treated with placebo and bisphosphonate. To test these hypotheses, a two-study will be conducted. In years 1-3, a 2-year randomized, placebo-controlled trial will be performed to determine if conventional periodontal therapy plus bisphosphonate will promote gains in clinical attachment and alveolar bone height in patients with adult periodontitis and low mandibular bone mass. In phase two (years 3-4), the bisphosphonate treatment group will be re-randomized to either hPTH (1-34) or placebo to determine whether addition of hPTH further restores bone mass and clinical attachment levels. Secondary outcomes include determining whether there is an association about specific IL-1 genotype and responsiveness to treatments. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MECHANISMS OF HORMONE THERAPY IN POSTMENOPAUSAL WOMEN Principal Investigator & Institution: Newby, L K.; Medicine; Duke University Durham, Nc 27706 Timing: Fiscal Year 2001; Project Start 01-APR-1999; Project End 31-MAR-2004 Summary: The use of unopposed estrogen of combined estrogen/progestin therapy for primary and secondary prevention of coronary disease events in post- menopausal women is gaining favor in the United States. Support for this practice is based largely on epidemiological association of a reduction in the risk of death and non-fatal myocardial infarction in populations of women mostly without prior coronary artery disease who took estrogen for a variety of reasons. The effects of adding a progestin to estrogen are less well studied. Because the potential public health impact from treatment of postmenopausal women with hormone replacement therapy for prevention of coronary artery disease events is enormous, it is imperative to establish a fund of knowledge that supports and aids in the interpretation of clinical trials data to help establish the group

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or groups for whom treatment should be recommended and when it should be initiated. To accomplish these goals we propose: 1. Using non-invasive measurement of vascular reactivity, to quantify the effect on vascular endothelial function of the addition of progesterone to estrogen therapy in post-menopausal women with and without coronary artery disease. 2. To study the effect of various combinations of postmenopausal hormone therapy on the coagulation system. 3. To use accumulated clinical trials databases to study clinical factors that may influence the efficacy of hormone replacement therapy for secondary prevention of coronary artery disease in postmenopausal women. The propose work will provide additional understanding of the mechanism of estrogen action on endothelial function (which is postulated to be the major mechanism of the beneficial effects of estrogen) and the effects of adding progestins to estrogen replacement regimens. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MENOPAUSE AND MIDLIFE AGING EFFECTS ON SLEEP DISORDERS Principal Investigator & Institution: Young, Terry B.; Professor of Prventative Medicine; Population Health Sciences; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2002; Project Start 15-JAN-1997; Project End 31-DEC-2006 Summary: (provided by applicant): The long-range goals of this ongoing longitudinal study of midlife aging in women are to accurately quantify the associations of menopause with the development and progression of sleep apnea and diminished sleep quality and to identify factors that influence the associations. Understanding the role of menopause in the development of sleep apnea and diminished sleep quality has important clinical and public health significance. Sleep apnea and diminished sleep quality are associated with significant cardiovascular morbidity, depression, and decrements in daytime performance. Because menopause will become a persistent state in nearly every woman during her lifetime, even a small effect on sleep apnea and insomnia, the major sleep disorders, would translate into significant morbidity. Furthermore, if associations are causal, understanding whether hormone replacement therapy or other factors significantly modify a menopause-sleep disorder link may lead to interventions that could reduce the occurrence and severity of sleep disorders in midand later life. The proposed study is designed to: 1) Test the hypothesis that changes over the continuum of pre to post menopause increase the incidence and progression of sleep disordered breathing, adjusted for baseline age, body composition, and other potential confounders, 2) investigate the effects of change in body composition during midlife on associations of menopause and sleep apnea, 3) quantify the risk of insomnia, hypersomnia and diminished sleep quality attributable to early, middle and late perimenopause and post menopause, 4) investigate protective effects of hormone replacement therapy on sleep problems, and 5) investigate genetic vulnerability to diminished sleep quality during menopause. To accomplish these aims, we propose additional research on our unique longitudinal cohort of midlife women, with 7-15 years of previously collected polysomnographic and other data with a) new data collected from overnight in-laboratory protocols with polysomnography conducted at 4-year intervals on 621 women enrolled in the Wisconsin Sleep Cohort Study, b) new data collected semi-annually by in-home polysomnography and other procedures and monthly diaries on menstrual characteristics and sleep problems on a subset of 280 women over their pre to peri to post menopausal years. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MONITORING CHEMOTHERAPY IN PROSTATE CANCER BY PROTON NMR Principal Investigator & Institution: Zakian, Kristen L.; Sloan-Kettering Institute for Cancer Res New York, Ny 10021 Timing: Fiscal Year 2001; Project Start 01-JAN-2000; Project End 31-DEC-2002 Summary: (Adapted from applicant's abstract): The overall goal of this project is to evaluate the use of proton NMR spectroscopic imaging (1H-MRSI) as a surrogate marker to non-invasively detect residual tumor after non-adjuvant androgen ablation + chemotherapy and to assess the effectiveness of chemotherapy in prostate cancer. The specific aims of the study are: 1. To determine whether the data from pre-treatment 1HMRSI of the prostate correlates with neo-adjuvant hormone+chemotherapy outcome as measured by the presence and extent of residual disease in surgical specimens. 2. To determine whether the 1H MRSI data at the chemotherapy midpoint (2 months) or changes in this data between the baseline and 2 months can predict the presence and extent of residual disease after 4 months of treatment with chemotherapy+hormone therapy. 3. To determine whether the 1H-MRSI data after four months of chemotherapy+hormone therapy predicts the presence and extent of residual disease at surgery. The subjects of the study are prostate cancer patients who have clinically localized prostate cancer at diagnosis, but are considered to have a high risk of recurrence after surgery or radiotherapy alone based on elevated PSA and/or Gleason grade. These patients are taking part in a clinical trial of neo-adjuvant androgen ablation plus chemotherapy with the hope of improving prognosis after surgery or radiotherapy. MRI and 1H-MRSI employing an endorectal probe will be performed on consenting patients on three occasions: (1) prior to neo-adjuvant hormone+chemotherapy, (2) at the midpoint of the treatment and (3) at the end of the treatment. Choline, creatine, and citrate will be mapped at 6.1 mm spatial resolution in order to assess the presence and extent of cancer. 1H-MRSI results will be compared to step-section histopathology of surgically resected prostate specimens. Significance Prostate cancer is common and unpredictable. Because of the location of the prostate gland, and the morbidity associated with its surgical removal (urinary incontinence, impotence) alternatives to surgical removal are of great practical significance to the practice of urology in males. PSA measurements have allowed early diagnosis, but staging of the disease and predicting the few disastrous cases (as compared to the many indolent cases) remains a major challenge comparable to early detection and cure of breast cancer in women. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MUTATIONS, THROMBOEMBOLISM

HORMONE

THERAPY,

AND

VENOUS

Principal Investigator & Institution: Psaty, Bruce M.; Professor, Medicine and Epidemiology; Medicine; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2001; Project Start 30-SEP-1998; Project End 31-AUG-2004 Summary: (Adapted from Investigator's Abstract) Epidemiologic studies have identified Factor V Leiden as the most common cause of heritable thrombophilia a prothrombotic mutation associated with a 5 to 7-fold increase in the risk of venous thromboembolism (VTE). In pre-menopausal women, the use of oral contraceptives is associated with a 4fold increase in VTE risk, and the joint effects of oral contraceptive use and Factor V Leiden carriership increase the VTE risk of by a factor of 35 (95% IC = 8 154). Recently, the results of several observational studies and randomized clinical trials suggest that in post-menopausal women, the use of hormone replacement therapy is associated with a

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3-fold increase in VTE risk. Whether post-menopausal women with prothrombotic mutations experience a similar 20-fold increase in risk when they take post-menopausal hormones remains unknown. The primary aim of this ancillary study is to assess the interaction between hormone replacement therapy and the prothrombotic mutations, Factor V Leiden and the recently described prothrombin mutation (20210A) on the incidence of VTE in a population-based case-control study conducted at Group Health Cooperative of Puget Sound (GHC). The investigators state that using a variety of computerized surveillance systems at GHC will enable them to identify both in-patient and out-patient episodes of venous thromboembolism. They anticipate recruiting 300 post-menopausal women with a first episode of objectively confirmed venous thromboembolism, and 1,200 population-based controls will be identified and recruited from the GHC enrollment files. Controls will be frequency matched to the cases on age and calendar-year. Data collection includes a review of ambulatory medical record and a telephone interview. The GHC computerized pharmacy database will be used to assess exposure to hormone replacement therapy. A venous blood specimen will be obtained from consenting subjects, processed into aliquots of white cells, plasma, and red cells, and stored at 70 degrees C prior to laboratory analysis. DNA will be extracted from white cells, and molecular genotyping assays will be conducted to assess carriership of prothrombotic mutations. Data from these various sources will be entered, linked and analyzed to address the specific aims. Under an additive model, the expected joint effects of HRT and carriership of prothrombotic mutations is 7. Compared with the null hypothesis for the additive model of a joint effect of 7, the investigators have 80% power to detect a difference between the alternative hypothesis of 18 and the null hypothesis of 7. If there is an important interaction between hormone replacement therapy and prothrombotic mutations, such a finding would offer important opportunities of VTE risk reduction by pre-treatment screening in the clinical setting for the prothrombotic mutations. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NEUROBIOLOGICAL EFFECT OF LONG-TERM ESTROGEN REPLACEMENT Principal Investigator & Institution: Smith, Yolanda R.; Assistant Professor; Obstetrics and Gynecology; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002; Project Start 15-JUN-2002; Project End 31-MAY-2007 Summary: (provided by applicant): This Mentored Patient-Oriented Research Career Development Award proposal contains didactic coursework, mentored instruction, and a clinical research project designed to apply the principles learned. The investigators' clinical research interest is in the integration of reproductive endocrinology with cognition, aging, and brain function and neurochemistry. The proposed clinical training and research studies in this application are designed to increase her skills in study design, biostatistics, cognitive neurosciences and neuroimaging techniques, with the ultimate goal of developing into an independent clinical investigator. The curriculum of the K30 Training Grant in Clinical Research, leading to a Master of Science in Clinical Research Design and Statistical Analysis at the UM, is included in the coursework. The goal of the research proposal is to study the neurobiological effects of long-term hormone therapy in healthy postmenopausal women. Sixty postmenopausal women, 60 years or older, will be recruited for this cross-sectional study (20 will never have used hormones, 20 will have used estrogen only for at least 10 years, and 20 will have used estrogen and progestin for at least 10 years). All women will undergo an extensive

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neuropsychological testing battery, a single photon emission computed tomography (SPECT) scan with a marker of cholinergic synaptic terminal density, an anatomic magnetic resonance image (MRI), and measures of estradiol and estrone. Ten women from each group will also undergo a functional MRI (fMRI) during a cognitive task designed to activate brain areas affected by estrogen and altered in Alzheimer's Disease. Comparison between groups will offer a greater understanding of the effect of hormone therapies on brain neurochemistry and cognition. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NSABP MEMBER: MICHIGAN STATE UNIVERSITY Principal Investigator & Institution: Scholnik, Aaron P.; Medicine; Michigan State University 301 Administration Bldg East Lansing, Mi 48824 Timing: Fiscal Year 2001; Project Start 12-DEC-1980; Project End 31-JAN-2006 Summary: The Michigan State University Cancer Consortium (MSUCTC) consists of the community campuses of MSU along with community cancer programs across the state, with leadership and coordination at the main MSU campus. The MSUCTC is currently treating and following 1,105 patients on long-term NSABP protocols. Accrual to protocols will continue to increase by four mechanisms: 1) Increasing the scientific and logistic support for currently active community oncologists; and 2) Recruitment of additional oncologists and surgeons to the MSUCTC. Our administrative efforts will focus on: 1) Increasing the presence of the main campus NSABP staff in the activities of our widely dispersed communities (e.g., tumor boards, grand rounds, physicians and nursing seminars, etc.); 2) Clinical trials infrastructural support by increasing local audits in order to eliminate protocol violations and decrease delinquencies; 3) Development of a specific NSABP web site for MSU affiliates; 4) Participation in pilot research projects; 5) As in the past, our group will continue to participate extensively in the NSABP activities (PI member of the board, breast committee, colon committee, protocol design group, audit group, and nursing committee. The MSUCTC has been concerned about quality of life issues, therefore, our plans are to design a pilot study of the cognitive effects of adjuvant therapy which will serve as a model for a larger NSABP trial. In addition, we will be conducting a study of acceptance and compliance with NSABP protocols in Native American communities in Michigan which will help the group design a strategy for approach to accrual of this population. Our institution has a special program to foster and monitor accrual of ethnic minorities to NSABP trials supported by NIH supplemental grants. This experience will be conveyed to the NSABP. Having a well-developed laboratory, equipped with HPLC, GLC, and Mass Spectroscopy apparatuses, our institution will offer to the group additional studies related to drug and hormone metabolites. Recently, MSU has formed a strong group developing targeted therapy. We have detected substantial changes in MAP-kinases during chemotherapy (including use of surrogate tissues) which will serve as a basis for designing pilot studies during the execution of NSABP protocols. We are in the process of preparation of a pilot protocol with patients on protocol B-30 which will be submitted to the NSABP for approval. An interdisciplinary group at MSU is studying the interrelations and abberations of cell cycle regulatory genes and gene products and their effect on tumor progression from non-invasive (DCIS) to invasive and metastatic disease. This may help to predict biologic behavior as well as treatment response. These two areas of research complement each other and may help the group design protocols with pharmacogenomic elements. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ORAL /LEIOMYOMA

CONTRACEPTIVES

/ENDOGENOUS

SEX

STEROIDS

Principal Investigator & Institution: Sweet, Stephanie; Meharry Medical College 1005-D B Todd Blvd Nashville, Tn 37208 Timing: Fiscal Year 2003; Project Start 10-JUL-2003; Project End 30-JUN-2008 Summary: The presence of uterine leiomyomas, benign smooth muscle tumors of the uterus, has long perplexed clinicians and the patients who develop them. Their enigmatic appearance is usually silent, but in some women they can precipitate substantial symptoms that do not consistently respond to medical therapy. Leiomyomas develop almost exclusively in women during their reproductive years and their growth, seems to be influenced by endogenous sex steroids. Our hypothesis is that the addition of exogenous hormones via oral contraceptives will accelerate the growth rate of leiomyomas. This supposition is important because, to date, a key component of various medical treatments for menorrhagia caused by leiomyomas are the use of oral contraceptives. Additionally, Black women, who are believed to produce higher levels of estrogens and progestins during the menstrual cycle, have a greater propensity for developing leiomyomas. The oral contraceptives could, therefore, have an additive affect. Studies to determine the influence of leiomyoma growth by oral contraceptives have been largely speculative, conflicting, and infrequently used a case control study design. Their impact on the growth of leiomyomas in Black women, who have the largest percentage of these symptomatic tumors (3 times greater), has never been investigated. In our two-center, case-control observational study, we will directly monitor the growth of uterine leiomyomas in women using oral contraceptives by using serial ultrasound evaluations (every 6 months for 36 months). In addition, all subjects will have serum and urine assays to establish if Black women produce higher levels of sex steroids. Our deliberate effort to recruit a large number of Black subjects provides an excellent opportunity to corroborate those findings. Women selected for this study will be premenopausal and have reproducible evidence of uterine leiomyomas. The case population (n=240) will consist of women using oral contraceptives and the controls (n=80) will be women who have never used hormonal therapy. The patient base in Meharry's urban center will be an abundant resource for the inclusion of Black case subjects sufficient to detect if there truly is a racial difference in this populations' leiomyoma growth rate. This collaborative effort will be a monumental step in ascertaining if oral contraceptive pills accelerate leiomyoma growth. Additionally, this will become a landmark study evaluating the seemingly exaggerated growth of leiomyomas in Black women and possibly correlating that growth difference with their increases in hormone levels. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: OSTEOPOROSIS IN OLDER MEN AND WOMEN Principal Investigator & Institution: Greenspan, Susan L.; Professor of Medicine; Medicine; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2003; Project Start 01-JAN-2003; Project End 30-NOV-2007 Summary: (provided by applicant): Susan Greenspan, M.D., Professor of Medicine at University of Pittsburgh, is applying for the K24 Midcareer Investigator Award in Patient-Oriented Research to advance her career in clinical investigations of osteoporosis in older men and women. Her immediate career objectives are 1) to establish herself as a leading national authority on osteoporosis in the elderly with a new focus on older men,

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and 2) to serve as a mentor for medical trainees, including medical students, fellows, and junior faculty members pursuing patient-oriented research in osteoporosis and related geriatric fields. Her long-term objectives are 1) to apply the expertise and skills in patient-oriented osteoporosis research to clinical research in other fields involving common endocrine or geriatric syndromes, and 2) to actively participate in the institutional commitment to promote clinical research at the University of Pittsburgh through mentoring and teaching activities. Dr. Greenspan's research will center on two areas. First, she will explore novel treatments with combination therapy with antiresorptive and anabolic agents for postmenopausal osteoporosis. New techniques assessing outcomes of trabecular vs. cortical bone density and markers of bone turnover will be utilized. Secondly, a model of male osteoporosis will be examined-that of bone loss following androgen deprivation therapy in men with prostate cancer. She will examine the pathophysiology of this bone loss and its prevention. Dr. Greenspan has a strong track record in mentoring junior investigators. This award would ensure protected time for mentoring activities that provide appropriate direction, resources, and educational programs for her trainees. Furthermore, this proposal will allow protected time for the candidate's self education for additional training in statistical analysis, the essentials of mentoring, involvement of African American subjects in clinical research, and leadership in academic medicine for women. The clinical research and mentoring program will be conducted at the University of Pittsburgh, which has a strong institutional commitment to the professional development of the candidate and a mission to support patient-oriented activities of its faculty members. The General Clinical Research Center (Dr. Greenspan's clinical laboratory), the Center for Minority Health, and the recently funded Clinical Research Training Award (K30) will help facilitate this proposal. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: OVARIAN FAILURE IN LH/HCG RECEPTOR KNOCKOUT ANIMALS Principal Investigator & Institution: Rao, Ch V.; Professor and Director; Obstetrics and Gynecology; University of Louisville University of Louisville Louisville, Ky 40292 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2006 Summary: Both IIpo Huhtaniemi's and our group recently succeeded in generating LH receptor knockout mice by gene targeting in embryonic stem cells. Although this gene knockout was not lethal, it rendered animals infertile. While ovaries of wild- type and heterozygous animals contained LH receptors, ovaries of homozygous littermates contained none. Also, while ovaries of wild-type and heterozygous animals were normal in size and contained preovulatory follicles and corpora lutea, the ovaries of homozygous littermates were small and pale with an arrest of follicular growth at the antral stage. Preliminary studies indicated this arrest could, at least partly, be due to a decrease in telomerase levels and a consequent increase in apoptosis. In homozygous animals, LH levels were markedly elevated, FSH levels were moderately elevated, and estradiol and progesterone levels decreased but were not totally suppressed. Knockout animals can be extremely useful in answering a number of unknowns in LH biology. For example, we could learn: 1) whether LH actions are required for the presence of normal numbers of primordial, primary, preantral and antral follicles; 2) whether FSH can induce follicular growth and ovulation in the total absence of LH actions; 3) what role LH signaling plays in ovarian development and function from one week after birth through one year of age; 4) what ovarian actions of LH are mediated by estradiol, progesterone and testosterone; 5) identify and characterize previously unidentified

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Hormone Therapy

ovarian genes that are regulated by estradiol, progesterone, testosterone, LH or by their combination; and 6) whether using gene therapy to introduce LH receptors into ovaries of null animals makes them cyclic and ovulate but still not get pregnant because they do not have LH receptors in the uterus. These are only a few examples of how the use of null animals could advance our current understanding on the role of LH in different ovarian functions. We propose three specific aims in this application: 1) Investigate structural and functional defects in ovaries of 7-day, 25-day, 60-day and 1-year old null mice to compare with their age- matched, wild-type and heterozygous siblings. 2) Investigate whether estradiol, progesterone and testosterone replacement therapy can correct structural and functional defects in ovaries of LH receptor knockout animals. 3) Determine whether retroviral mediated LH receptor gene transfer can correct structural and functional defects in ovaries of null animals so they become cyclic and ovulate even though pregnancy may not occur due to the absence of LH receptors in the uterus. There are several strengths in this proposal. Foremost is studying LH biology using knockout technology. Second is using steroid hormone replacement and gene therapies. Third is using cDNA expression arrays, a powerful technique in gene expression analysis. All techniques to be used in the proposed studies have already been established to obtain preliminary data presented in the proposal. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PARACRINE DYSREGULATION OF OOCYTE COMPETENCE IN PCOS Principal Investigator & Institution: Dumesic, Daniel A.; Professor; Mayo Clinic Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2007 Summary: (provided by applicant): Polycystic ovary syndrome (PCOS) in women is characterized by anovulation, LH hypersecretion, hyperandrogenism and insulin resistance. As the most common endocrinopathy in females, affecting 4-7% of reproductive-aged women, and as a frequent cause of infertility, accounting for 75% of anovulation, PCOS has staggering adverse physiological, psychological and financial consequence on reproduction in women. During gonadotropin stimulation for in vitro fertilization (IVF), PCOS women experience decreased fecundity and increased pregnancy loss. Since experimental investigation of oocyte and embryo development in humans is limited by ethical constraints, we have developed the prenatally androgenized (PA) female rhesus monkey as a model for PCOS. PA female monkeys undergoing follicle stimulating hormone (FSH) therapy for IVF exhibit LH hypersecretion, circulating insulin excess, an exaggerated shift in intrafollicular steroidogenesis from estradiol (E2) and androstenedione (A4) to progesterone (P4), and impaired embryo development beginning with embryonic genome activation. Because insulin enhances FSH-induced granulose cell differentiation, leading to LH-induced P4 production, we hypothesize that a) premature follicle luteinization and b) impaired oocyte developmental competence in PA monkeys are caused by adverse effects of hyperinsulinemia on follicle maturation. We predict that such abnormalities in PA monkeys are reversed by improved insulin sensitivity from weight loss through dietary restriction and will test our prediction in Specific Aims 1 and 2. Based upon data from our recognized nonhuman primate model of PCOS, we also hypothesize that c) premature follicle luteinization is a cause of poor oocyte developmental competence in PCOS women undergoing FSH therapy for IVF. We predict that granulosa cell dysregulation of LH receptor, insulin receptor (IR) and growth differentiation factor-9 (GDF-9) transcription from premature follicle luteinization causes poor cumulus cell

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proliferation in PCOS women (Specific Aim 3). We further hypothesize that d) meiotically-competent and meiotically-incompetent oocytes of PCOS patients are impaired in expression of GDF-9 and other developmentally relevant messenger ribonucleic acids (mRNAs) (Specific Aim 4). The long-term objectives of this proposal are to: 1) define molecular markers of oocyte developmental competence that enhance IVF pregnancy outcome by improving rates of embryo cleavage and blastocyst formation; while minimizing pregnancy loss in women with PCOS and other insulin resistant states, such as obesity and Type II diabetes, and 2) to provide additional, unique, insight into the transgenerational effect of PCOS. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RECEPTORS

PATHOBIOLOGY

OF

BREAST

CANCER

AND

HORMONE

Principal Investigator & Institution: Press, Michael F.; Professor; Pathology; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033 Timing: Fiscal Year 2001; Project Start 01-APR-1988; Project End 31-JAN-2004 Summary: (adapted from the investigator's abstract) Molecular alterations in human breast cancer have provided both a better understanding of the disease process and an important rationale for clinical decision-making. Estrogen receptor (ER) and progesterone receptor (PR) were among the first alterations in any solid cancer wich proved to be clinically important. ER and PR have been shown to be correlated with clinical outcome and with responsiveness to hormonal therapies. Considerable evidence indicates that another receptor, HER-2/neu, is equally important in breast cancer specimens. HER-2/neu amplification and overexpression have been correlated with shorter disease-free interval and shorter overall survival in both node-positive and node-negative disease. Some investigators have not been able to confirm these clinical outcome correlations in their studies. They have addressed a number of potential problem areas with clinical correlation studies in an effort to resolve some controversy surroundings the clinical utility of HER-2/neu. Issues related to study design, especially sample size, sensitivity and specificity of analytic methods used for gene amplification / overexpression and the potential confounding effect of differential treatment responsiveness, have been considered. During the current funding period several studies were performed to address these issues. A wide range of antibody immunoreactivities were demonstrated among 28 different HER-2/neu antibodies in paraffin-embedded tissue specimens with known gene amplification and expression levels which were characterized in frozen specimens by Southern, Norther and Western blot analysis and immunohistochemical staining. The most sensitive antibodies were identified and used in additional studies. A method for quantitation of HER-2/neu protein using molecularly engineered cells and computerized image analysis was described and tested. Fluorescence in situ hybridization (FISH) was shown to be suitable for gene amplification studies in archival clinical specimens. Two retrospective studies of HER-2/neu, gene amplification or expression were conducted in women with axillary lymph-node negative breast cancer. Both studies were restricted to women who had no adjuvant radiation therapy, chemotherapy or hormone therapy and both studies demonstrated a significant correlation between HER-2/neu, alteration and poor clinical outcome. Similar correlations between poor survival and HER-2/neu amplification/overexpression were demonstrated in studies of patents with endometrial cancer and salivary gland carcinoma. Currently and in our proposal for the future renewal period, we are addressing issues related to HER-2/neu receptor as a predictor of responsiveness to treatment. In a preliminary, prospective study of taxol (paclitaxel)

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Hormone Therapy

chemotherapy in women with recurrent or metastatic breast cancer we have observed a correlation between HER-2/neu overexpression and prolonged overall survival. Paradoxically, this suggests greater responsiveness to taxol chemotherapy among breast cancers which overexpress a marker or more aggressive disease. A prospective clinical trial of HER-2/neu as a predictor of responsiveness to chemotherapy is proposed. A retrospective study of HER-2/neu as a predictor of tamoxifen responsiveness is also planned. These studies should lead to a greater understanding of this molecular genetic alteration and its use in clinical management decisions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PHYTOESTROGENS AND PROGRESSION OF ATHEROSCLEROSIS Principal Investigator & Institution: Hodis, Howard N.; Associate Professor; Medicine; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033 Timing: Fiscal Year 2003; Project Start 22-SEP-2003; Project End 31-MAY-2008 Summary: (provided by applicant): The fear and discontent with traditional hormone replacement therapy (HRT) coupled with the interest in natural products has resulted in an increased use of soy protein as a postmenopausal therapeutic alternative by both women and their physicians alike. Evidence from epidemiological and non-human primate studies indicate that isoflavone-rich soy protein has antiatherogenic activity, evidence supported by a large body of data that indicate mechanistic and biologic plausibility. No studies to our knowledge have been published or proposed to determine the long-term effects of soy protein on the progression of atherosclerosis in postmenopausal women. We propose to conduct a 2.5-year, randomized, double-blind, placebo-controlled trial of isoflavone-rich soy protein in 300 healthy postmenopausal women without clinical evidence of cardiovascular disease. We hypothesize that relative to placebo, isoflavone-rich soy protein (supplying genistein, daidzein and glycitein) will reduce the progression of subclinical atherosclerosis in healthy postmenopausal women. The primary end point will be the progression of subclinical atherosclerosis measured as the rate of change in common carotid artery intima-media thickness in computer image processed B-mode ultrasonograms, a well-established noninvasive arterial imaging end point for antiatherosclerosis trials, lsoflavone-rich soy protein may provide a safe and effective alternative approach for extending premenopausal cardioprotection afforded by endogenous estrogen into menopause without the increased risk of thromboembolic events and certain cancers associated with traditional HRT. Since many postmenopausal women are using soy products to maintain their health, it is important to understand whether soy protein has an antiatherogenic effect so that women can make a truly informed decision concerning their expectations of this form of postmenopausal therapy. The question as to whether soy protein is effective in reducing the progression of atherosclerosis in postmenopausal women is not only timely, but also of immense medical and financial importance since atherosclerosis remains the number I killer of postmenopausal women. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PKC AS A MARKER IN TAMOXIFEN RESISTANT BREST CANCER Principal Investigator & Institution: Tonetti, Debra A.; Assistant Professor; Pharmaceutics/Pharmacodynamics; University of Illinois at Chicago 1737 West Polk Street Chicago, Il 60612 Timing: Fiscal Year 2002; Project Start 04-SEP-2002; Project End 31-AUG-2004

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Summary: (provided by applicant): Resistance to tamoxifen (TAM), the most often prescribed endocrine treatment for breast cancer, represents a significant problem in the management of the disease. Identification of the key factors involved in the molecular mechanism of TAM resistance will undoubtedly lead to the development of logical therapeutic targets. We have previously reported that stable transfection of protein kinase C alpha (PKCa) into T47D human breast cancer cells results in a hormoneindependent phenotype and TAM-resistant tumor growth. Tumors formed from these cells grow in the presence of TAM and regress in the presence of 17Beta-estradiol (E2). Our finding that a pure antiestrogen can inhibit these TAM-resistant tumors may have important implications for the treatment of TAM-resistant breast cancer. This information may now allow us to predict the efficacy of endocrine therapy. For example, tumors overexpressing PKCa may be stimulated to grow if the patient is given TAM therapy, therefore a more appropriate therapy may be an estrogen-like compound or a pure antiestrogen. However our T47D/PKCalpha tumor model cannot determine whether PKCalpha overexpression occurs in patients prior to TAM exposure, or is a result of long-term TAM treatment. The following Specific Aims provide the framework to substantiate the role of PKCalpha as a predictor or as a marker of TAM treatment failure as well as elucidate the downstream genes that may participate in TAM-resistant breast cancer. 1. To determine whether PKCalpha expression is predictive of TAMtreatment failure. We will perform immunohistochemical analysis to determine PKCalpha expression in paraffin-embedded breast cancer specimens obtained from the National Cancer Institute's Cooperative Breast Cancer Tissue Resource (NCI CBCTR). 2. To determine whether PKCa expression increases in recurrent (TAM-resistant) tumors relative to the primary tumor. We propose to study paired biopsies from patients from the Lynn Sage database at NMH where both primary and recurrent paraffin-embedded tumors are available to identify changes, if any, in the intensity and/or frequency of PKCalpha expression by immunohistochemistry. 3. Identify specific genes that are differentially expressed downstream of PKCa that mediate the hormone-independent phenotype in T47D:A18/PKCalpha cells and tumors. To examine the PKCa-mediated signaling pathway we will utilize our T47D:A18/PKCalpha cell culture and tumor model to investigate differential gene expression as determined by Atlas Gene Array technology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: POST ABDOMINAL FAT

MENOPAUSAL

HORMONE

THERAPY

AND

INTRA

Principal Investigator & Institution: Gower, Barbara A.; Associate Professor; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2001; Project Start 01-DEC-2000; Project End 30-NOV-2001 Summary: Background: Hormonal and metabolic changes associated with the menopause may confer increased risk for cardiovascular disease (CVD). Data indicate that the postmenopausal period is associated with increases in total and central ("android") body fat; increases in the atherogenic components of the blood lipid profile; and deterioration of glucose tolerance - all risk factors for CVD. Changes in lipid and glucose metabolism may be secondary to accumulation of central fat, particularly intraabdominal fat (IAF), the compartment associated with dyslipidemia and insulin resistance. Hormone replacement therapy has positive effects on the lipid profile in postmenopausal women, and may affect regional fat deposition. However, the extent to which the beneficial effects of hormone therapy on disease risk factors are mediated by changes in fat distribution is not known. Few studies have examined the effects of

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Hormone Therapy

hormone replacement therapy on body composition and fat distribution, and non have examined the effect of exogenous hormones on IAF, the adipose compartment most closely associated with disease risk. Objective: To test the hypothesis that hormone replacement therapy (HRT, combined estrogen-progestin) in postmenopausal women decreases risk by limiting IAF deposition. The proposed research will examine the effect of HRT on total, regional, and intra-abdominal fat deposition, and on the relationships between adiposity, the plasma lipid profile, and glucose metabolism. Design: Longitudinal cohort study of 140 early postmenopausal women using or not using HRT. A baseline assessment (within the first year of hormone use) and one 2-year follow-up assessment will be conducted. Total body fat will be assessed with dual-energy X-ray absorptiometry, hydrodensitometry, and deuterium dilution; and regional adiposity (thigh, abdominal, intra-abdominal) will be quantified with computed tomography. Circulating levels of total cholesterol, high- and low-density lipoprotein cholesterol, and triglycerides will be determined. Insulin sensitivity and glucose tolerance will be assessed with the tolbutaminde-modified, frequently-sampled, intravenous glucose tolerance test and minimal modeling. Significance: HRT reduces risk and incidence of CVD in postmenopausal women. This study will determine if HRT reduces disease risk by influencing fat distribution and decreasing IAF. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: POSTMENOPAUSAL HORMONE REPLACEMENT THERAPY AFTER CABG Principal Investigator & Institution: Ouyang, Pamela C.; Associate Professor of Medicine; Medicine; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2001; Project Start 15-AUG-1996; Project End 31-JUL-2004 Summary: Coronary atherosclerosis is a major cause of death in women in the USA. Although coronary artery bypass surgery decreases symptomatic and clinical evidence of ischemia, it does not alter the underlying process. Patients may present several years later with recurrent symptoms that may be a result of occlusion of saphenous vein grafts, development of atherosclerotic disease in the vein grafts, or progression of underlying disease. Any intervention that can reduce the rate of progression of coronary atherosclerosis following bypass surgery would provide significant benefit for women following bypass surgery and possibly for other women with atherosclerotic disease. Observational studies suggest that postmenopausal estrogen replacement therapy is associated with a reduction in cardiac morbidity. However the benefit for hormone replacement therapy in women with established coronary disease has not been demonstrated. This randomized, double-blind controlled trial tests the hypothesis that postmenopausal hormone replacement therapy in women following coronary bypass surgery will reduce the occurrence of graft occlusion and delay the development of graft atherosclerosis. Women will be randomized to esnadiol with daily medroxyprogesterone or placebo within 4 weeks of bypass surgery. Graft occlusion and development of vein graft atherosclerosis will be measured by comparing quantitative coronary angiographic and intravascular ultrasonographic assessment of disease severity and extent performed at 6 months and 3.5 years after randomization. The primary outcome variables will be the occurrence of graft occlusion at 6 months and the change in severity and extent of atherosclerosis in the saphenous vein grafts over 3 years. The proposal will determine th influence of hormone replacement therapy on the primary outcome variables. The pathophysiologic mechanisms of interest in this proposal are platelet activation, fibrinogen binding to platelets, vascular reactivity, coagulation and fibrinolytic factors and lipoprotein composition. The proposal will test

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the hypothesis that these variables predict the occurrence of graft occlusion and rate o development of graft atherosclerosis. The proposal also tests the hypothesis that hormone replacement therapy exerts its beneficial effects by its effects on those risk factors in addition to more traditional risk factors including the lipids and lipoprotein profile. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: POSTMENOPAUSE CHD RISK: PLATELET GENES & HORMONE THERAPY Principal Investigator & Institution: Bray, Paul F.; Professor; Medicine; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2003; Project Start 27-SEP-2003; Project End 31-AUG-2007 Summary: Coronary heart disease (CHD) is the number one killer of women in the United States. Hormone replacement therapy (HRT) with estrogen (E) and progesterone (P) should probably no longer be considered cardioprotective. In fact, data from the HERS and WHI studies indicate E+P may increase myocardial infarction (MI) and stroke despite its beneficial effects on cholesterol levels. Since blood platelets play a central role in the pathophysiology of MI and stroke, these findings raise questions about the effect of HRT on platelet thrombus formation in coronary vessels. Our published and preliminary data show that 1) female platelets are hyperreactive compared to male platelets, 2) sex hormones enhance platelet reactivity, 3) platelets express estrogen receptor (ER) beta and ER alpha, 4) functional platelet polymorphisms are risks for CHD, and 5) there are pharmacogenetic interactions between functional polymorphisms of platelet genes and specific cardiovascular therapies (aspirin, statins, and GPIIb-Illa blockers). Because women are at least as predisposed as men to genetic influences on CHD development, we hypothesize that inherited platelet variants dictate which postmenopausal women are susceptible to the prothrombotic effects of HRT. Our goal in this proposal is to identify genetic predictors of CHD events in women. We will perform a case-control study on the Observational Study of the Women's Health Initiative, analyzing DNA from 1,060 women who have experienced a CHD death or documented nonfatal MI (cases) and from 2,120 controls not having a CHD event. With this large number of CHD cases and controls we will test for associations between functional platelet polymorphisms and CHD events (Aim 1) and interactions between these polymorphisms and HRT as a risk for CHD events (Aim 2). We have assembled an excellent group of investigators and have an extremely valuable resource, putting us in a unique position to achieve these goals and our long-term goal of optimizing the prevention and management of CHD in women. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PRENATAL GLUCOCORTICOID AND POSTNATAL BLOOD PRESSURE Principal Investigator & Institution: Figueroa, Jorge P.; Associate Professor; Obstetrics and Gynecology; Wake Forest University Health Sciences Winston-Salem, Nc 27157 Timing: Fiscal Year 2002; Project Start 01-DEC-2001; Project End 30-NOV-2006 Summary: (provided by applicant): During development, glucocorticoids (GC) are essential for organ maturation, particularly the fetal lung. In 1994 an NIH consensus panel recommended the use of glucocorticoids for enhancing fetal lung maturation in pregnancies threatened by premature labor between 24 and 34 weeks of gestation. As a consequence, the use of GC given as single or multiple doses has increased from 15

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percent to more than 50 percent in such pregnancies. The possibility that GC may have adverse effects has prompted the questioning of the growing use of GC in the perinatal period. Our working hypothesis is that maternal GC therapy to promote fetal lung maturation has a fetal programming effect on the kidney that will appear as hypertension later in life. Specifically, our hypotheses are: 1) Antenatal administration of synthetic GC predisposes the individual to hypertension in adult life; 2) Exposure to synthetic GC, at critical periods during fetal life, disrupts nephrogenesis resulting in kidneys with a reduced number of nephrons; 3) Synthetic GC disrupts nephrogenesis by downregulating the fetal ReninAngiotensin-System (RAS); 4) The intrarenal mechanism involved in the effects of synthetic GC on the fetal RAS includes inhibition of COX-2 and Type I NOS in macula densa and the downregulation of angiotensin AT1 and AT2 receptors in renal tissue; 5) Reduction in nephron number during fetal life results in hypertension during adulthood. We will test these hypotheses by administering single or multiple clinically relevant doses of betamethasone to pregnant sheep at a gestational age equivalent to that used in clinical practice (0.6 of gestation). To specifically test whether reducing nephron mass at this specific stage of development produces hypertension in adults, we will perform fetal unilateral nephrectomy at 0.6 of gestation and monitor blood pressure and renal function at selected intervals after birth until adulthood. In addition, using molecular biology tools we will study potential mechanisms by which GC may alter fetal kidney development. Specifically, we will study the expression of the RAS system and of two important regulators of this system during fetal development, i.e., Type I NOS and PGHS-2. These data will provide important information on the potential impact of prenatal GC administration on blood pressure in adult life and the mechanism by which GC exerts this effect. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PREVENTION OF STERIOD INDUCED OSTEOPOROSIS IN CHILDREN Principal Investigator & Institution: Green, Rebecca P.; Pediatrics; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2001; Project Start 01-JUL-2001; Project End 31-MAY-2006 Summary: (Taken from the applicants abstract): Glucocorticoid-induced bone disease is an under addressed and potentially devastating problem in the pediatric population. Less than half of the patients on chronic steroid therapy will sustain at least one nontraumatic fracture. In addition, glucocorticoid therapy during childhood may reduce peak bone mineral density, increasing the risk of osteoporotic fractures later in life. Although bisphosphonates appear to be effective at preventing glucocorticoid induced bone loss in adults, the safety and efficacy, of these drugs for the treatment glucocorticoid induced bone disease in children is not known. Children are unique due to the potential adverse effects on growing bone. The long-term objectives of this study are to determine if a bisphosphonate, pamidronate, can be safely and effectively used to treat and prevent glucocorticoid mediated bone loss in children. Specific aim 1 is designed to test the hypothesis that pamidronate in combination with calcium and vitamin D is more effective then calcium and vitamin D alone at treating existing glucocorticoid induced bone disease. It is a 24-month single-blind, placebo-controlled study. Specific aim 2 is designed to test the hypothesis that pamidronate in combination with calcium and vitamin D, initiated within 90 days of initiating glucocorticoid therapy, is more effective then calcium and vitamin D alone at preventing a decrease in bone density in children anticipated to require long term glucocorticoid therapy. It is a 12-month single- blind, placebo-controlled study with a 12-month post-treatment

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follow-up period. The primary endpoint of specific aim 1 and 2 is volume corrected lumbar spine bone mineral density (BMD). Secondary endpoints include proximal femur and whole body BMD, fractures, markers of bone turnover, growth, and skeletal changes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PROGESTERONE AND SLEEP IN OLDER WOMEN Principal Investigator & Institution: Moe, Karen E.; Psychiatry and Behavioral Scis; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2002; Project Start 01-FEB-2002; Project End 31-DEC-2004 Summary: Sleep complaints increase significantly with age in women. Many older women experience difficulty falling asleep, more night-time awakenings, and less restful sleep. Sleep studies verify that disturbed sleep patterns are observed even in healthy older women. Sleep disturbances are associated with increased daytime drowsiness, increased accident risk, increased use of health care, and reduced quality of life. Older women receive a disproportionate number of sedative-hypnotic medications, which can exacerbate sleep apnea and have daytime carryover effects such as sedation, falls and subsequent fractures, and cognitive impairment. A better understanding of the sleep changes experienced by older women is sorely needed. One contributing factor may be menopause-related changes in sex steroids such as estrogen and progesterone. Research attention has focused on estrogen. However, progesterone may also participate in the control of sleep. Clinical reports indicate that women often feel drowsy after they take oral progesterone - an effect which is undesirable during the day, but may be positive at night. To date there are no published studies of progesterone's effect on the objectivelymeasured sleep and daytime drowsiness of older women. The proposed study will take a systematic, multi-dimensional approach to determining the effect of progesterone on the sleep and drowsiness of older women. Objective techniques (polysomnography, Multiple Sleep Latency Test) will be used to measure sleep and daytime drowsiness following evening or morning administration of 300 mg micronized progesterone, in 40 postmenopausal women who are at least 5 years past menopause and who are not experiencing hot flashes. Attention, memory, subjective sleepiness, and blood levels of progesterone and its metabolite (allopregnanolone) will also be measured. This study is part of a long-term research plan to assess (1) how the very low postmenopausal levels of estrogen and progesterone contribute to sleep difficulties of older women, and (2) how hormone replacement therapy affects the sleep of women. An ongoing placebocontrolled study is investigating the effects of estrogen on the sleep of older women. The proposed study will complement the estrogen study. It will enhance our limited understanding of the relationship between sex steroids and sleep, and the factors that contribute to sleep problems in older women. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PROGESTERONE THERAPY FOR WOMEN WITH EPILEPSY Principal Investigator & Institution: Herzog, Andrew G.; Associate Professor of Neurology; Beth Israel Deaconess Medical Center St 1005 Boston, Ma 02215 Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 31-AUG-2003 Summary: (Applicant's Abstract): This randomized, placebo-controlled, double-blind, multicenter clinical trial will assess the efficacy of adjunctive cyclic progesterone therapy in lessening the frequency of intractable seizures in women with localization related epilepsy. There is considerable scientific evidence to suggest that estrogen generally

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increases while progesterone decreases neuronal excitability and seizures. Preliminary open trials suggest that the cyclic administration of adjunctive natural progesterone supplement may lessen seizure frequency by over 50% in the majority of women with catamenially exacerbated intractable seizures. Oral synthetic progestins, in contrast, have not shown significant efficacy. Progesterone is not widely used as an adjunct to seizure management because its benefits have yet to be definitively demonstrated. The proposed clinical trial will require 640 subjects. During the baseline phase, seizure/menstrual charts will document baseline seizure frequency and determine if seizure occurrence shows a catamenial pattern of exacerbation. The subjects will be divided into catamenial and non-catamenial groups. Each group will be randomized in a 2:1 ratio into progesterone and placebo treatment groups. Seizure frequency during 3 months of treatment will be compared to baseline, while monitoring antiepileptic drug and hormone levels. The proposed clinical trial has considerable potential significance for women with epilepsy. Approximately 30% of women with epilepsy have refractory seizures, that is persistent seizures despite trials of antiepileptic drug, use. It is estimated that 35% of these women have catamenial seizure exacerbation. If, on the basis of preliminary observations, this group responds favorably to hormonal therapy, one would expect that progesterone may benefit approximately (1,000,000 x.30 x.35) 100,000 women with catamenial epilepsy and perhaps many more women with no a priori demonstrated hormonal sensitivity to seizure occurrence. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RADIOPHARMACEUTICALS FOR BREAST TUMOR IMAGING & THERAPY Principal Investigator & Institution: Katzenellenbogen, John A.; Professor; Chemistry; University of Illinois Urbana-Champaign Henry Administration Bldg Champaign, Il 61820 Timing: Fiscal Year 2001; Project Start 01-JAN-1984; Project End 31-DEC-2003 Summary: Most breast tumors contain estrogen receptors (ER) that regulate tumor cell growth and mediate the action of estrogen antagonists such as tamoxifen. Not all breast cancers, however, respond to hormone therapy. Therefore, it is important to have effective prognostic tools that will identify those patients most likely to be hormone responders, so that they can be treated with this well tolerated therapy, whereas those unlikely to respond can promptly begin regimens of radiation of chemotherapy. The presence of ER in most breast tumors provides a mechanism for selective localization of estrogens, which if labeled with suitable radionuclides, could be used for diagnostic imaging or radiotherapy or breast tumors. During past periods of support on this project, we have developed a series of estrogens labeled with fluorine-18 and carbon-11, some of which are effective agents of imaging estrogen receptor positive (ER+) tumors. Other investigators have developed other adiohalogenated estrogens for ER-mediated radiotherapy. Other investigators have developed other radiohalogenated estrogens for ER-mediated radiotherapy. Also, recent investigations have revealed that another estrogen receptor subtype, ERbeta, is present in some target tissues, including breast tissue and tumors. We have three goals of the next phase of this project: (1) We intend to develop ER ligands for breast tumor imaging that are labeled with the readily available radionuclide, technetium-99m, as well as its rhenium congener. To accomplish this, we will investigate novel aspects of technetium organometallic chemistry through the application of three new methods for the preparation of cyclopentadienyl tricarbonyl technetium and related systems. These functionalities will be incorporated are pendant and integral groups into steroidal and non-steroidal ER ligands. (2) Based on emerging

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differences in the structure-binding affinity relationships for ERalpha and ERbeta ligands, derived in part from our investigations, we will prepare ligands selective for these receptors and develop them as tumor imaging agents. (3) We will utilize several radionuclides (iodine-123, and 124 and bromine-76, 77, the later three available to use through a collaboration to prepare ER ligands for radiotherapy, and we will have these tested in appropriate animal tumor model systems. These investigations should lead to substantial advances in the availability of diagnostic imaging gents for ER+ tumors and ER subtype- selective imaging agents, to the evaluation in vivo of radiotherapeutic ER ligands. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REDUCTION OF TRIGLYCERIDES IN WOMEN ON HRT Principal Investigator & Institution: Kuller, Lewis H.; Professor and Chair; Epidemiology; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2001; Project Start 01-SEP-2001; Project End 31-AUG-2006 Summary: (provided by applicant): The risk and benefits of hormone replacement therapy (HRT) have come under increased concern in recent years because of the results of the HERS and WHI trials, the increased risk of breast cancer, new therapies, i.e., SERMs and lipid lowering drugs, bisphosphorates, and better understanding of hormone metabolism and disease. We have shown in several studies that the potential benefits of HRT are limited by lifestyle, cofactors, specifically weight gain, obesity and increased visceral abdominal fat associated metabolic changes in lipoproteins, inflammatory markers and estrogen metabolites. We are proposing a randomized trial of 500 women, on HRT for at least two years, aged 52-60 years, and three or more years postmenopausal to test whether reduction in waist circumference, triglycerides, dense LDLc, number of LDL particles, CPR, PAI-I by aggressive diet exercise, versus a health education control will decrease progression or result in regression of measures of subclinical vascular disease. The intervention is designed to reduce total fat intake to 17 percent of calories, 1300 kilo calories, and increase moderate activity to 150-240 minutes per week to obtain a 10 percent reduction in weight. The primary endpoint will be a 20 percent or at least a 20 mg decrease in triglyceride levels, a 5 cm decrease in waist circumference, and a 10 percent decrease in LDLc. This will result in changes in subclinical measurements including carotid ultrasound, electron beam computer tomography of the coronary and aorta, pulse wave velocity, endothelial function, and tonometry of the radial artery. NMR spectroscopy of lipoproteins, inflammatory markers, and estrogen metabolites will also be evaluated. Therefore, the primary goal of this trial is the modification of measures of subclinical disease among HRT users. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: RELAXIN-LIKE FACTOR IN MALE GONADAL DEVELOPMENT Principal Investigator & Institution: Schwabe, Christian; Professor; Biochem and Molecular Biology; Medical University of South Carolina 171 Ashley Ave Charleston, Sc 29425 Timing: Fiscal Year 2001; Project Start 01-APR-2001; Project End 31-MAR-2006 Summary: (Scanned from the applicant's abstract) In about 3.5 percent of newborn human males the gonads are undescended (chryptorchidism), a condition that leads to infertility and is associated with a high rate of testicular cancer. In the absence of any effective drugs, surgery is used widely to correct that condition. While surgery allows

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gonadal development to progress to fertility, it appears that the increased threat of testicular cancer is not reduced correspondingly. These are persuasive reasons to study the physiology and biochemistry of testicular development and explore the possibility of drug design to eliminate the defect and, with it, the propensity for testicular cancer formation. RLF (relaxin-like factor), which appears to be an absolute requirement for testicular development, is presently the best candidate for therapeutic intervention in the neonate. RLF can be detected in the sera of prepubertal children (0.3 ng/mL) but rises at puberty to 1.2 ng/mL in males only. Selective deletion of the RLF gene causes infertility in mice, and injection of our anti-RLF antibodies into pregnant rats, 5 days pre-partum, caused retention of testicles in the body cavity at 20 days of age when all the control animals had totally descended gonads. There can be no doubt that RLF is a necessary component of the regulatory chain of events for gonadal development and that absence of or a defect in the RLF gene or the RLF receptor gene may be the cause of the developmental disturbance in segments of our population. Our work will highlight the role RLF is playing in these processes and will significantly improve the prospects for a drug to treat cryptorchidism. We intend to use specially designed synthetic RLF derivatives and anti-RLF antibodies to study the process of gonadal development and to examine the prospects of substitution therapy. RLF is a small molecule of about 6,300 Dalton, which will pentrate the intestinal wall of the neonate and enter the bloodstream so that gonadal complications detected at birth could be treated immediately by dietary supplement. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RESEARCH RESOURCES CORE D--METABOLIC FUNCTION AND BODY COMPOSITION Principal Investigator & Institution: Yarasheski, Kevin E.; Associate Professor; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2001; Project Start 01-DEC-2000; Project End 30-NOV-2001 Summary: This study involves two protocols: 1) the extent to which frail, old men (n=80) can respond to 9 months of exercise training with the cardiovascular, musculoskeletal, and central nervous system adaptions that have been shown to occur in younger people and 2) if hormone replacement therapy (HRT) can reduce frailty in old women (n=120) with physical frailty, and to determine if 9 months of exercise training brings about greater improvements in old women who have been on HRT for 9 months than in sex hormone deficient women. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ROLE OF MELATONIN IN SECONDARY INSOMNIA IN THE ELDERLY Principal Investigator & Institution: Gooneratne, Nalaka S.; Medicine; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 31-AUG-2005 Summary: Chronic insomnia affects up to 30% of the elderly and significantly impairs quality of life and daytime functioning. It is often secondary to other medical conditions, such as pain from osteoarthritis. Recent work has suggested that melatonin, a neurohormone produced by the pineal gland and regulated by the suprachiasmatic nucleus, the primary circadian pacemaker, is decreased in elderly insomniacs. However, treatment trials in primary insomniacs have been equivocal. This has raised many questions regarding the function of melatonin such as its role in sleep-wake regulation

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and whether it has nocturnal sleep-promoting effects. Interestingly, pain and nonsteroidal anti-inflammatory drugs blunt melatonin rhythms. Thus, I believe that melatonin secretion is impaired in the elderly with chronic pain and that this contributes to their insomnia. To address the hypothesis, the applicant proposes the following aims: 1) A case-control study to test the hypothesis that melatonin deficiency is a risk factor for insomnia in the elderly with osteoarthritis pain and identify a threshold level to distinguish melatonin deficient patients; 2) A randomized, double-blind, placebo controlled trial of melatonin replacement therapy in elderly insomniacs with osteoarthritis pain to test the hypothesis that melatonin deficiency is a causal factor for their development of insomnia. Analysis will include univariable and multivariable models, and receiver operator curve analysis for Aim 1, and comparison of melatonin vs. placebo treatment arms on l objective parameters for Aim 2. This protocol may provide new insights into the neurohormonal risk factors for the development of insomnia, test the model that melatonin deficiency is a causal factor for insomnia, provide a mechanistic basis for targeted melatonin replacement therapy, and provide the training necessary to conduct rigorous, independently-funded, patient-oriented research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ROLE OF THE CELL CYCLE IN HYPERSENSITIVITY TO ESTRADIOL Principal Investigator & Institution: Santen, Richard J.; Professor of Medicine; Medicine; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904 Timing: Fiscal Year 2001; Project Start 01-JAN-2000; Project End 31-DEC-2003 Summary: Hormone dependent breast cancers initially respond to endocrine therapy with tumor regression but tumor recurrences are invariable. An understanding of the mechanisms mediating relapse would allow development of strategies to counteract this process. We have provided evidence that tumor cells adapt during treatment by becoming hypersensitive to estradiol, a process which mediates tumor re-growth. We wish to determine precisely what steps induce this adaptive process. Preliminary data suggest a key role for cell cycle events distal to estrogen receptor function. Our hypothesis is that an adaptive process occurs in which growth factor and estradiol mediated events cooperatively interact at a "point of intersection" in the cell cycle to mediate hypersensitivity. At this "intersection point," c-myc, a direct estrogen-mediated early response gene, and products of the growth factor stimulated RAS pathway cooperate to regulate key cell cycle proteins. We postulate that this interaction results in suppression of the cyclin inhibitor p-27, bypass of the need for phosphorylation of the Rb protein, enhanced activation of E2F transcription factors, and an increase in cyclin E kinase activity. To test this hypothesis, we will pursue four specific aims using as a model, breast cancer cells with adaptive hypersensitivity. Specific Aim 1 will evaluate the role of E2F transcription factors and the cyclins in the process of adaptive hypersensitivity. Specific Aim 2 will seek to demonstrate down regulation of cyclin inhibitors and resultant effects on E2F levels and cell proliferation. We postulate that adaptation to estrogen deprivation involves down regulation of inhibitors of cyclin dependent kinase activation. We will measure the levels of the two classes of inhibitors, the INK 4 a-d group as well as the Cip-1/Waf-1/Kip1/Kip2 class (p-2l, p-27, p-57). To directly assess cause and effect relationships, we will use stable transfectants to determine if p-27 activation decreases sensitivity to estradiol in LTED deprived cells. Specific Aim 3 will evaluate the role of growth factor pathways on E2F production. We will use strategies both for induction of hypersensitivity in wild type cells and for reversion of hypersensitive cells back to normal sensitivity. Inhibitors of MAP kinase

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and RAS plasma membrane binding will be used to interdict the effects of activated RAS in hypersensitive cells and to cause reversion of hypersensitivity. induction of hypersensitivity in wild type cells will involve TGF alpha administration as well as use of tetracycline regulatable, stable transfection constructs to cause over-expression of MAP kinase. Specific Aim 4 will determine whether LTED deprivation induces antiapoptotic regulatory mechanisms. These studies are expected to identify appropriate targets which could then be used in patients to revert hypersensitive cells back to normal and thereby enhance the duration of hormonal therapy in women with breast cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: S179D PROLACTIN: INHIBITION OF PROSTATE CANCER GROWTH Principal Investigator & Institution: Walker, Ameae M.; None; University of California Riverside 900 University Ave Riverside, Ca 92521 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-AUG-2005 Summary: (Provided by the applicant) Prostate cancer is the second leading cause of cancer deaths among males in the United States. While effective treatments exist for as long as the tumors remain sensitive to androgens, there are no good therapies available once evolution to an androgen-insensitive state occurs. An evaluation of factors which contribute to the growth of these later stage tumors is crucial to the development of new therapeutic strategies. Prolactin (PRL) is one such factor. Although large quantities of PRL are produced by the pituitary, PRL also serves as an autocrine growth factor in the normal human prostate and, as we have shown, this autocrine growth loop continues to be operative in cells representative of highly metastatic, androgen-independent cancers. Using a novel PRL growth antagonist developed in our laboratory, S179D PRL, we have demonstrated that blockade of the PRL autocrine growth loop reduces both the growth of well-established tumors and tumor initiation when androgen-independent cancer cells are grown in nude mice. This PRL growth antagonist therefore has the potential to be an important new therapeutic for late stage disease. The overall aim of the proposed project is to gain a fuller understanding of the molecular and cellular mechanisms underlying S179D PRL's antagonism of prostate tumor growth so that the full potential of this therapeutic can be realized. The specific aims are 1) to determine the optimal dose of S179D PRL, 2) to establish whether S179D PRL slows or halts growth or actually reduces tumor size, 3) to determine whether resistance can develop, and 4) to determine whether any aspect of the growth inhibition involves a) the promotion of apoptosis, or b) downregulation of the growth-promoting PRL autocrine loop, or c) upregulation of the short PRL receptor. In most experiments tumor size will be monitored by the amount of a secreted transfected gene product in the urine. In this way, individual nude mice can be assessed for their response to treatment. S179D PRL will be administered by Alzet minipumps implanted subcutaneously. Molecular and cellular effects on the tumors/tumor cells will be assessed by end-labeling for apoptosis, Northern, Western and microarray analysis for gene expression and immunoprecipitation, Western and radiolabel incorporation for signaling. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SAFETY OF EB1089 IN EARLY RECURRENT PROSTATE CANCER Principal Investigator & Institution: Feldman, David; Stanford University Stanford, Ca 94305

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Timing: Fiscal Year 2001; Project Start 01-DEC-2000; Project End 30-NOV-2001 Summary: The active hormonal form of vitamin D, 1,25-hydroxyvitamin D3 [calcitriol] inhibits the growth of prostate cancer cells both in vitro and in vivo in animals. We have demonstrated, in a pilot study, that calcitriol therapy is beneficial in the treatment of patients with early prostate cancer. However, dose dependent hypercalciuria and hypercalcemia limits the amount of calcitriol that can be administered safely. A series of synthetic analogs of calcitriol are equal or greater in their ability to inhibit the growth of prostate cancer cells while being less calcaemic in vivo. EB-1089, manufactured by Leo Pharmaceutical Products, is one such calcitriol analog. The goals of the proposed study are to determine whether therapy with EB-1089 in prostate cancer patients improves the disease course. The specific therapeutic strategy planned is a prospective, multi-center, randomized, double-blind, placebo-controlled, phase III trial of EB-1089 treatment of patients with rising prostate specific antigen [PSA] values following radical prostatectomy. Stanford/Palo Alto VA will be one of four study sites; other sites are Baylor College of Medicine, Cedars-Sinai UCLA Medical Center, and the University of Pittsburgh School of Medicine. 21 of a total of 84 subjects will be enrolled at Stanford and the Palo Alto VA. Individuals who have recurrences of prostate cancer after prostatectomy as indicated by at least one rising post-prostatectomy PSA measurement. Initial PSA levels between 1 and 20 ng/ml will ensure that patients have smaller tumor burdens and thus represent early recurrences. Study subjects must be free of metastatic disease. Qualifying volunteers will be randomized to either EB-1089 treatment or placebo. After an initial dose-finding phase that will last 4 weeks, individuals will be maintained on therapy in a double-blind fashion for a total of 6 months of treatment. Following this, all study participants will be treated with active drug for an additional three months in an unblinded fashion. PSA levels will be monitored during the study period. PSA levels in patients with early recurrent prostate cancer continue to rise in a predictable manner until meaningful therapy is initiated. Each subject thereby acts as his own control, however there will be a separate control group as well. The rising PSA, expressed as a doubling time, in the period prior to treatment will be compared to the doubling time during the EB-1089 treatment period. We expect thatEB-1089 will slow or stabilize the rate of rise of PSA and increase the doubling time. Efficacy of EB-1089 will be established if the PSA doubling time is increased in a larger proportion of subjects in the EB-1089 treated group than the placebo group. If over a 9 month EB-1089 treatment period, the doubling time is not stabilized or improved, the patients will be turned back to their urologist/oncologist to select among other treatment options available. Since during this period there is as yet no clear-cut superior treatment regimen, we feel this intervention will not preclude other useful therapeutic modalities and will not deprive the patients of meaningful therapy. Ultimately, EB-1089 and similar agents may become useful agents in treating recurrences of prostate cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SAFETY OF ESTROGEN IN LUPUS ERYTHEMATOSUS Principal Investigator & Institution: Buyon, Jill P.; Professor; Hospital for Joint Diseases Ortho Inst Orthopaedic Institute New York, Ny 10003 Timing: Fiscal Year 2001; Project Start 30-SEP-1995; Project End 31-AUG-2006 Summary: (provided by applicant): The Safety of Estrogens in Lupus Erythematosus, National Assessment (SELENA) consists of two randomized double blind placebocontrolled equivalence trials. The first examines the effect of hormonal replacement therapy (HRT) on disease activity in postmenopausal women with SLE, the primary outcome being severe flare. Current enrollment is 314 patients and should reach the

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target of 350 by April 2001. The second trial, initiated in April 1997, examines the effect of oral contraceptive pills (OCP) on disease activity. To date, 159 subjects have been enrolled at an average rate of month. This application seeks an additional 5 years of enrollment for the OCP trial to achieve adequate power for assessing equivalence in severe flare rates across treatment arms; determining potential salutary effects of estrogens on two clinical concerns in SLE, osteoporosis and atherosclerosis; and studying two research themes often linked to estrogen use, autoimmunity and thrombosis. Three new investigations have been added to the proposal, each of which optimally utilizes the unique resources of this prospective clinical trial. These complementary projects have a dual purpose: to evaluate hormonal effects in vitro with respect to fundamental pathophysiologic questions, and to determine whether laboratory markers can be established to select subsets of patients who may either benefit from OCP or be at increased risk for exacerbation of 1upus or cardiovascular sequelae. Accordingly, 4 specific aims are proposed in this application. Specific Aim 1: To evaluate the safety of OCP by assessing whether the rates of severe flare in the OCP and placebo groups are clinically equivalent. Specific Aim 2: To assess protection from and risk of osteoporosis and atherosclerosis by pre- and post-study evaluation of DEXA scans, fasting lipids, fibrinogen, CRP, plasminogen activator inhibitor, homocysteine, lipoprotein(a), and carotid duplex. Specific Aim 3: To understand whether there is a change in B cell subsets in the peripheral blood of SLE patients receiving OCP; whether there are changes in expression of candidate autoimmunity genes in peripheral blood B cells (including SHP-1, VCAM-1, Bcl-2, and CD22); and whether there are changes in the number or phenotype of B cells spontaneously secreting anti-DNA antibody. Specific Aim 4: To address the hemostatic effects of estrogen (with focus on the protein S system) which may increase the risk for thrombosis even in patients screened out by virtue of high levels of anticardiolipin antibodies or a lupus anticoagulant. The SELENA-OCP trial offers the best (and perhaps only) opportunity to firmly answer the concerns of clinical safety and potential cardiovascular and skeletal efficacy of exogenous hormones in women with SLE. Moreover, this translational research trial, at least with regard to the estrogen and progesterone load imposed by OCP, will facilitate answers to the everpressing basic biologic issues of the effect of female hormones on autoimmunity and thrombosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SELECTIVE ESTROGEN MODULATORS AND COGNITION Principal Investigator & Institution: Herndon, James G.; Associate Research Professor; None; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2002; Project Start 16-APR-2002; Project End 31-MAR-2006 Summary: Estradiuol (E2) replacement therapy (ERT) in menopausal women has protective effects on a variety of age-related diseases, including osteoporosis, cardiovascular diseases, age-related memory impairments, and development of dementia. However, ERT, even with progestin co- treatment, induces precancerous changes in the tissues of the breast and uterus. A new group of non-steroidal estrogens, deemed Selective Estrogen Receptor Modulators (SERMs) has been developed as a possible alternative to ERT but without the adverse proliferative effects on breast and endometrial tissues, while retaining some of the positive effects of E2. Yet, despite the well-documented efficacy of these compounds in peripheral target tissues, their influence in the brain, and especially upon cognitive function, is not known. Clearly brain and cognitive effects of SERMs must be understood in order to determine their desirability as an alternative to ERT in hypoestrogenic women. We will use the

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ovariectomized rhesus monkey as a model of human low-estrogen conditions, such as menopause, to examine the effects of SERMs on female cognition. This project will first determine whether the SERMs tamoxifen and raloxifene are E2 agonists or E2 antagonists in a variety of cognitive domains in Ovariectomized female rhesus monkeys. Monkeys will be repeatedly tested with a computerized touch- screen system on a battery of four memory and attentional tasks while undergoing E2, SERMs, or placebo treatments. Specific Aim 2ill use the same battery of tasks to determine whether SERMs, in the presence of E2, act as E2 antagonists on cognitive function. Specific Aim 3 will use positron emission tomography (PET) and the glucose metabolic tracer [18F]fluorodeoxyglucose (18F FDG) to determine whether E2 increases activation of specific brain regions following performance on the cognitive task most improved by ERT. Specific Aim 1 will determine whether SERMs mimic E2 in enhancing object recognition memory, attention, and working memory, while impairing spatial memory functions in ovariectomized female rhesus monkeys. Specific Aim 2 will determine whether SERMs, in the presence of E2, act a sE2 antagonists in cognitive function/ Specific Aim 3 will use PET and the 18F FDG tracer to evaluate the relationships between rCMRglc, ERT, and cognitive performance on a specific task. These data in the rhesus monkey will provide valuable information on the efficacy of SERMs on female cognition and will help in evaluating the risks and benefits of using these compounds in hypoestrogenic women. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SEX POSTMENOPAUSE

STEROIDS

AND

MAMMOGRAM

DENSITY

IN

THE

Principal Investigator & Institution: Greendale, Gail A.; Associate Professor; Medicine; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2001; Project Start 01-JUN-1998; Project End 31-MAR-2003 Summary: (Adapted from Investigator's Abstract) Epidemiologic studies find that increased mammographic density is an independent risk factor for breast cancer and the magnitude of risk associated with mammographic density is greater than that associated with almost all other known risk factors for breast cancer. This application focuses on 3 major questions: 1) are endogenous levels of sex steroids in postmenopausal women related to mammographic density; 2) does treatment with postmenopausal estrogen and estrogen/progestin therapy increase mammographic density; and 3) do the serum levels of estrone achieved as a result of treatment with postmenopausal hormone therapy predict change in mammographic density? To address these questions, the amount of density of mammograms performed during the Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial will be determined using a computer-based threshold technique. PEPI was a 3-year, randomized placebo controlled trial of conjugated equine estrogens (CEE) vs. CEE plus one of 3 progestin regimens, which enrolled 875 postmenopausal women aged 45-64 at baseline. Data already collected as part of PEPI that will be used in this project will include: endogenous sex steroids at baseline, PEPI treatment assignment, estrone serum levels on-treatment, and necessary covariates. The project will last 3 years and take place at 3 sites: UCLA, USC, and Bowman Gray. The specific aims are to: 1) measure the density of mammograms performed at baseline and 12 months; 2) determine whether baseline mammographic density is associated with endogenous levels of sex steroids; 3) quantify the relation between change in mammographic density and adherence to treatments; and 4) determine whether changes density are associated with serum levels of estrone achieved as a result of

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hormone therapy. By assessing density changes in mammograms with this computerbased method, which has been previously linked to a quantified increase in risk of breast cancer, it may be possible to assess how much of a risk-increase would be predicted by hormone use. The investigators state that this may serve as the first in a series of investigations that would allow identification of those women at higher risk of developing breast toxicity from postmenopausal supplemental hormone use. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SLEEP DISTURBANCE IN MENOPAUSE Principal Investigator & Institution: Freedman, Robert F.; Professor; Psychiatry & Behav Neuroscis; Wayne State University 656 W. Kirby Detroit, Mi 48202 Timing: Fiscal Year 2002; Project Start 01-JAN-2002; Project End 31-DEC-2006 Summary: At present, over 35% of the women in the United States have reached the median age of menopause, 51 years. Hot flashes (HFs) are the most common symptom of the climacteric and occur in the vast majority of postmenopausal women. Sleep disturbance has also been reported to be highly prevalent in this population. Yet, the causal links, if any, between these 2 phenomena are I not known. In the studies proposed here, we will attempt to discern the relationships among Hfs and objective and subjective sleep disturbance. In Study 1, we will record sleep and HF parameters in postmenopausal women with HFs, those without HFs, and age-matched premenopausal women without HFs. We will perform quantitative EEG analyses, use an objective test of daytime sleepiness (MSLT) and assess subjective sleep quality with established instruments. HF frequency increases with ambient temperature. If HFs produce arousals and thereby disrupt sleep, then reducing ambient temperature should improve sleep and increasing temperature should worsen it (Study 2). Increased arousal frequency has been found in postmenopausal women with HFs. If this accounts for reports of poor sleep, then experimental sleep disruption in asymptomatic women should produce reports of poor sleep, as well. In Study 3, we will use yoked groups of symptomatic and asymptomatic women and disrupt sleep of the latter group based on recordings from the former group. We will do this using a stimulus specific to HFs (ambient heating). Despite the common use of hormone replacement therapy, its effects on sleep have not been established. In Study 4, we will systematically manipulate ambient temperature during sleep in symptomatic women before and during estrogen replacement and in a placebo-control group. In Study 5, we will determine the effects of elevated sympathetic activation on HFs and sleep using a stimulus that does not, by itself, disrupt sleep (orthostasis). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: STAT3 IN ANDROGEN RECEPTOR SIGNALING IN PROSTATE CANCER Principal Investigator & Institution: Gao, Allen C.; Associate Member; Urology; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2001; Project Start 20-JUL-2001; Project End 31-MAY-2006 Summary: Most prostate cancer patients respond initially to androgen ablation and antiandrogen therapy. However, virtually all patients will relapse due to acquisition of the androgen-independent tumor cells. The molecular mechanisms characterizing prostate cancer progression from androgen-dependence to androgen-independence are incompletely understood. Androgen-independent activation of androgen receptor (AR) by cross-talk between AR and other signal pathways has been demonstrated to mediate

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prostate cancer androgen-independent progression in the absence of androgen. We previously demonstrated that overexpression of interleukin-6 (IL-6) is linked to prostate cancer progression accompanied by activation of Signal Transducers and Activators of Transcription 3 (Stat3) signaling. Further investigation in our laboratory demonstrated that Stat3 is constitutively activated in cells derived from both rat and human prostate cancers, and that Stat3 activation is correlated with malignant potential. In human prostate cancer cells, blockade of Stat3 expression suppressed proliferation in vitro and tumorigenicity in vivo. In addition, preliminary results demonstrate that the Stat3 signaling pathway interacts with the androgen receptor signaling pathway. Based on these results, we propose that Stat3 both regulates the expression of Stat3 target genes, and interacts with AR in prostate cancer cells. The experiments proposed in this application are based upon the hypothesis that Stat3 activation alters androgen receptor signaling pathway resulting in the loss of growth control in prostate cancer cells. Through our proposed analysis of the role of Stat3 activation in AR signaling in prostate cancer cells, we seek to provide a possible mechanism for the development of the androgen-independent prostate cancer cells. To accomplish this goal, we will examine the role of Stat3 activation in AR signaling in prostate cancer cells by establishing prostate cancer cell lines expressing constitutively activated Stat3 and examining the effect of Stat3 activation on androgen response in prostate cancer cells. We will then determine the molecular basis of interactions between Stat3 and the AR signaling. Finally, we will examine the association between Stat3 activation and prostate cancer progression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TREATMENT OF CROHN'S DISEASE WITH GROWTH HORMONE Principal Investigator & Institution: Hannon, Tamara S.; Pediatrics; Indiana UnivPurdue Univ at Indianapolis 620 Union Drive, Room 618 Indianapolis, in 462025167 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): It is the investigator's career goal to obtain a faculty position in an academic medical center where she expects to develop an independent research program. A Research Career Award will not only allow for the development of enhanced research skills and knowledge from implementing the clinical research project, but will allow for formal didactic training in the basic skills required to develop expertise as an academic independent clinical researcher. Through participation in the IU Clinical Investigator Training Enhancement Program, she will receive the didactic training necessary for a career in clinical research. The environment at the IU School of Medicine (IUSM) is outstanding and she has been given full support from the Director of Pediatrics and the Director of the GCRC. She expects to develop expertise in the use of state-of-the-art metabolic techniques for investigating clinical endocrine questions. The proposed project aims to assess medical outcomes of growth hormone (GH) and GH releasing hormone (GHRH) therapy in patients with Crohn's disease. To date, there are limited data on the efficacy of GH in Crohn's disease. GHRH is a peptide that stimulates the synthesis and secretion of GH from the somatotrope cells of the anterior pituitary gland and is used therapeutically in some GH deficient patients. Interestingly, GHRH is also naturally found in the gut. It is not known if GHRH has local actions in the gut. It is hypothesized that treatment with human GH will be beneficial to patients with Crohn's disease by decreasing disease severity, improving growth, enhancing protein synthesis, and increasing bone mineral density. Furthermore, she hypothesizes that GHRH will have a comparable effect on protein synthesis and bone mineral density. It will possibly have a greater effect on disease severity because of the

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possibility that it may have local effects in the gut. The purpose of this study is to test these hypotheses in a prospective, randomized, double-blind clinical trial. The objectives of the study are to assess medical outcomes of the treatment, to evaluate growth, to measure bone turnover and bone density, to access changes in body composition, and to evaluate whole body proteolysis and protein synthesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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

A preliminary study of growth hormone therapy for Crohn's disease. Author(s): Slonim AE, Bulone L, Damore MB, Goldberg T, Wingertzahn MA, McKinley MJ. Source: The New England Journal of Medicine. 2000 June 1; 342(22): 1633-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10833209&dopt=Abstract

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A prospective, observational study of postmenopausal hormone therapy and primary prevention of cardiovascular disease. Author(s): Grodstein F, Manson JE, Colditz GA, Willett WC, Speizer FE, Stampfer MJ. Source: Annals of Internal Medicine. 2000 December 19; 133(12): 933-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11119394&dopt=Abstract

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A review of intravenous versus oral vitamin D hormone therapy in hemodialysis patients. Author(s): Mazess RB, Elangovan L. Source: Clinical Nephrology. 2003 May; 59(5): 319-25. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12779092&dopt=Abstract

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

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A woman attempting to discontinue hormone therapy. Author(s): Kleerekoper M. Source: Jama : the Journal of the American Medical Association. 2002 November 13; 288(18): 2264; Author Reply 2264-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12425697&dopt=Abstract

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A woman attempting to discontinue hormone therapy. Author(s): Freedman RR. Source: Jama : the Journal of the American Medical Association. 2002 November 13; 288(18): 2264; Author Reply 2264-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12425696&dopt=Abstract

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Adjuvant hormone therapy after radiation or surgery for localized or locally advanced prostate cancer. Author(s): See WA. Source: Curr Treat Options Oncol. 2003 October; 4(5): 351-62. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12941195&dopt=Abstract

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Adjuvant hormone therapy following primary therapy for endometrial cancer. Author(s): Loibl S, von Minckwitz G, Kaufmann M. Source: European Journal of Cancer (Oxford, England : 1990). 2002 November; 38 Suppl 6: S41-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12409070&dopt=Abstract

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Adjuvant hormone therapy in locally advanced and localized prostate cancer: three EORTC trials. Author(s): Bolla M, de Reijke TM, Zurlo A, Collette L. Source: Front Radiat Ther Oncol. 2002; 36: 81-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11842758&dopt=Abstract

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Advanced prostate cancer: immediate or deferred hormone therapy? Author(s): Newling D. Source: European Urology. 2001; 39 Suppl 1: 15-21. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11114596&dopt=Abstract

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Alterations in body composition and fat distribution in growth hormone-deficient prepubertal children during growth hormone therapy. Author(s): Roemmich JN, Huerta MG, Sundaresan SM, Rogol AD. Source: Metabolism: Clinical and Experimental. 2001 May; 50(5): 537-47. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11319714&dopt=Abstract

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Alterations of glucocorticoid receptor expression during glucocorticoid hormone therapy in renal transplant patients. Author(s): Berki T, Tavakoli A, Nagy KK, Nagy G, Nemeth P. Source: Transplant International : Official Journal of the European Society for Organ Transplantation. 2002 March; 15(2-3): 132-8. Epub 2002 March 09. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11935170&dopt=Abstract

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Amended report from the NAMS Advisory Panel on Postmenopausal Hormone Therapy. Author(s): North American Menopause Society. Source: Menopause (New York, N.Y.). 2003 January-February; 10(1): 6-12. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12544671&dopt=Abstract

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Are needle-free injections a useful alternative for growth hormone therapy in children? Safety and pharmacokinetics of growth hormone delivered by a new needle-free injection device compared to a fine gauge needle. Author(s): Dorr HG, Zabransky S, Keller E, Otten BJ, Partsch CJ, Nyman L, Gillespie BK, Lester NR, Wilson AM, Hyren C, van Kuijck MA, Schuld P, Schoenfeld SL. Source: J Pediatr Endocrinol Metab. 2003 March; 16(3): 383-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12705363&dopt=Abstract

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Aromatase inhibitor development and hormone therapy: a perspective. Author(s): Brodie A. Source: Seminars in Oncology. 2003 August; 30(4 Suppl 14): 12-22. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14513433&dopt=Abstract

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Asian trends in prostate cancer hormone therapy. Author(s): Akaza H, Naito S, Cheng C, Kaisary A, Soebadi DM, Umbas R, Esuvaranathan K, Gu FL, Zhou L, Hong SJ, Kim WJ, Lee SE, Rim JS, Song JM, Yoon JH, Chang SJ, Huang CH, Yang CR, Hirao Y, Murai M, Tsukamoto T, Usami M. Source: Gan to Kagaku Ryoho. 2002 November; 29(11): 1951-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12465395&dopt=Abstract

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Attenuation of posttraumatic muscle catabolism and osteopenia by long-term growth hormone therapy. Author(s): Hart DW, Herndon DN, Klein G, Lee SB, Celis M, Mohan S, Chinkes DL, Wolf SE. Source: Annals of Surgery. 2001 June; 233(6): 827-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11371741&dopt=Abstract

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Body composition abnormalities in children with Prader-Willi syndrome and longterm effects of growth hormone therapy. Author(s): Eiholzer U, l'Allemand D, van der Sluis I, Steinert H, Gasser T, Ellis K. Source: Hormone Research. 2000; 53(4): 200-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11044804&dopt=Abstract

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Breast cancer and post-menopausal hormone therapy. Author(s): Kenemans P, Bosman A. Source: Best Practice & Research. Clinical Endocrinology & Metabolism. 2003 March; 17(1): 123-37. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12763516&dopt=Abstract

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By the way, doctor. I'm 70. I took hormone therapy for a while after menopause, but stopped taking it long ago. My memory definitely isn't as good as it used to be. If I started taking estrogen again, would my memory improve? Author(s): Lee TH. Source: Harvard Health Letter / from Harvard Medical School. 2000 December; 26(2): 8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11114876&dopt=Abstract

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Calcium kinetics in children with osteogenesis imperfecta type III and IV: pre- and post-growth hormone therapy. Author(s): Vieira NE, Goans RE, Weiss GH, Hopkins E, Marini JC, Yergey AL. Source: Calcified Tissue International. 2000 August; 67(2): 97-100. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10920211&dopt=Abstract

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Can growth hormone therapy cause diabetes? KIMS Strategic Committee. Author(s): Monson JP, Bengtsson BA, Abs R, Feldt-Rasmussen U, Wuster C. Source: Lancet. 2000 May 13; 355(9216): 1728-9. Erratum In: Lancet 2000 June 3; 355(9219): 2000. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10905274&dopt=Abstract

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Carbohydrate metabolism is not impaired after 3 years of growth hormone therapy in children with Prader-Willi syndrome. Author(s): L'Allemand D, Eiholzer U, Schlumpf M, Torresani T, Girard J. Source: Hormone Research. 2003; 59(5): 239-48. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12714788&dopt=Abstract

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Cardiac performance in Turner's syndrome patients on growth hormone therapy. Author(s): Radetti G, Crepaz R, Milanesi O, Paganini C, Cesaro A, Rigon F, Pitscheider W. Source: Hormone Research. 2001; 55(5): 240-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11740146&dopt=Abstract

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Cardiovascular disease outcomes during 6.8 years of hormone therapy: Heart and Estrogen/progestin Replacement Study follow-up (HERS II). Author(s): Grady D, Herrington D, Bittner V, Blumenthal R, Davidson M, Hlatky M, Hsia J, Hulley S, Herd A, Khan S, Newby LK, Waters D, Vittinghoff E, Wenger N; HERS Research Group. Source: Jama : the Journal of the American Medical Association. 2002 July 3; 288(1): 4957. Erratum In: Jama 2002 September 4; 288(9): 1064. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12090862&dopt=Abstract

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Cardiovascular risk factors improve during 3 years of growth hormone therapy in Prader-Willi syndrome. Author(s): l'Allemand D, Eiholzer U, Schlumpf M, Steinert H, Riesen W. Source: European Journal of Pediatrics. 2000 November; 159(11): 835-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11079197&dopt=Abstract

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Changes in cyclosporine A levels in pediatric renal allograft recipients receiving recombinant human growth hormone therapy. Author(s): Sanchez CP, Salem M, Ettenger RB. Source: Transplantation Proceedings. 2000 December; 32(8): 2807-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11134812&dopt=Abstract

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Characteristics of growth hormone therapy for pediatric patients with brain tumors in the National Cooperative Growth Study (NCGS) and from a survey of pediatric endocrinologists. Author(s): Meacham LR, Sullivan K. Source: J Pediatr Endocrinol Metab. 2002 May; 15 Suppl 2: 689-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12092682&dopt=Abstract

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Combined hormone therapy and breast cancer: a single-edged sword. Author(s): Gann PH, Morrow M. Source: Jama : the Journal of the American Medical Association. 2003 June 25; 289(24): 3304-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12824214&dopt=Abstract

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Comparison of the effect of raloxifene and continuous-combined hormone therapy on mammographic breast density and breast tenderness in postmenopausal women. Author(s): Jackson VP, San Martin JA, Secrest RJ, McNabb M, Carranza-Lira S, FigueroaCasas P, Fernandes CE, Romaguera J. Source: American Journal of Obstetrics and Gynecology. 2003 February; 188(2): 389-94. Erratum In: Am J Obstet Gynecol. 2003 June; 188(6): 1628. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12592245&dopt=Abstract

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Continuation of growth hormone therapy versus placebo in transition-phase patients with growth hormone deficiency: impact on body composition, insulin sensitivity, and thyroid function. Author(s): Ann Intern Med. 2003 Jan 7;138(1):I10 Source: J Pediatr Endocrinol Metab. 2002 December; 15 Suppl 5: 1355-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12513063

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Counseling patients who elect to discontinue hormone therapy. Author(s): Simon JA, Mack CJ. Source: Int J Fertil Womens Med. 2003 May-June; 48(3): 111-6; Discussion 137-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12839141&dopt=Abstract

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Cyclic estrogen-progestin hormone therapy as a new therapeutic approach in the treatment of functional alterations of the hypothalamus-pituitary-ovary axis: case reports. Author(s): Trimarchi CP, Russo P. Source: Endocrine Research. 2002 August; 28(3): 155-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12489565&dopt=Abstract

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Cytologic aspects of the nasal respiratory epithelium in postmenopausal women treated with hormone therapy. Author(s): Caruso S, Roccasalva L, Di Fazio E, Sapienza G, Agnello C, Ficarra S, Di Mari L, Serra A. Source: Fertility and Sterility. 2003 March; 79(3): 543-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12620437&dopt=Abstract

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Dangers of growth hormone therapy in critically ill patients. Author(s): Ruokonen E, Takala J. Source: Current Opinion in Clinical Nutrition and Metabolic Care. 2002 March; 5(2): 199209. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11844988&dopt=Abstract

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Dangers of growth hormone therapy in critically ill patients. Author(s): Ruokonen E, Takala J. Source: Annals of Medicine. 2000 July; 32(5): 317-22. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10949062&dopt=Abstract

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Differential effects of growth hormone therapy in malnourished hemodialysis patients. Author(s): Kotzmann H, Yilmaz N, Lercher P, Riedl M, Schmidt A, Schuster E, Kreuzer S, Geyer G, Frisch H, Horl WH, Mayer G, Luger A. Source: Kidney International. 2001 October; 60(4): 1578-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11576376&dopt=Abstract

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Differential effects of unopposed versus opposed hormone therapy, tibolone, and raloxifene on substance p levels. Author(s): Kukuvitis A, Kourtis A, Papaiconomou N, Zournatzi V, Makedos G, Panidis D. Source: Fertility and Sterility. 2003 July; 80(1): 96-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12849808&dopt=Abstract

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Discontinuation of postmenopausal hormone therapy in a Massachusetts HMO. Author(s): Reynolds RF, Walker AM, Obermeyer CM, Rahman O, Guilbert D. Source: Journal of Clinical Epidemiology. 2001 October; 54(10): 1056-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11576818&dopt=Abstract

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Distinguishing atrophy and high-grade prostatic intraepithelial neoplasia from prostatic adenocarcinoma with and without previous adjuvant hormone therapy with the aid of cytokeratin 5/6. Author(s): Abrahams NA, Bostwick DG, Ormsby AH, Qian J, Brainard JA. Source: American Journal of Clinical Pathology. 2003 September; 120(3): 368-76. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14502799&dopt=Abstract

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Divergent effects of hormone therapy on serum markers of inflammation in postmenopausal women with coronary artery disease on appropriate medical management. Author(s): Zanger D, Yang BK, Ardans J, Waclawiw MA, Csako G, Wahl LM, Cannon RO 3rd. Source: Journal of the American College of Cardiology. 2000 November 15; 36(6): 1797802. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11092646&dopt=Abstract

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Docetaxel followed by hormone therapy after failure of definitive treatments for clinically localized/locally advanced prostate cancer: preliminary results. Author(s): Hussain A, Dawson N, Amin P, Naslund M, Engstrom C, Chen T. Source: Seminars in Oncology. 2001 August; 28(4 Suppl 15): 22-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11685725&dopt=Abstract

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Does growth hormone therapy harmonize distorted morphology and body composition in chronic renal failure? Author(s): Zivicnjak M, Franke D, Ehrich JH, Filler G. Source: Pediatric Nephrology (Berlin, Germany). 2000 December; 15(3-4): 229-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11149116&dopt=Abstract

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Does growth hormone therapy improve motor development in infants with PraderWilli syndrome? Author(s): Eiholzer U, Malich S, I'Allemand D. Source: European Journal of Pediatrics. 2000 April; 159(4): 299. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10789939&dopt=Abstract

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Does growth hormone therapy in adult patients with growth hormone deficiency protect against bone loss? Author(s): Brixen K, Hansen TB, Eriksen EF, Mosekilde L. Source: Growth Hormone & Igf Research : Official Journal of the Growth Hormone Research Society and the International Igf Research Society. 1998 February; 8 Suppl A: 81-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10993597&dopt=Abstract

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Does HER-2 status predict only a decreased response to hormone therapy in advanced breast cancer, or does it also predict the extent of metastatic disease? Author(s): Beltran M, Colomer R. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2002 December 1; 20(23): 4605; Author Reply 4606. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12454123&dopt=Abstract

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Does oral contraceptive use lead to hormone therapy use in women doctors? Our bodies, our choices, our practice. Author(s): Santoro NF. Source: Menopause (New York, N.Y.). 2003 March-April; 10(2): 109-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12627035&dopt=Abstract

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Early results of LH-RH agonist treatment with or without chlormadinone acetate for hormone therapy of naive localized or locally advanced prostate cancer: a prospective and randomized study. The Prostate Cancer Study Group. Author(s): Akaza H, Homma Y, Okada K, Yokoyama M, Moriyama N, Usami M, Hirao Y, Tsushima T, Ohashi Y, Aso Y. Source: Japanese Journal of Clinical Oncology. 2000 March; 30(3): 131-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10798540&dopt=Abstract

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Early risks of hormone therapy in patients with coronary heart disease. Author(s): Wenger NK, Knatterud GL, Canner PL. Source: Jama : the Journal of the American Medical Association. 2000 July 5; 284(1): 41-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10872009&dopt=Abstract

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Effect of chronic renal failure and growth hormone therapy on the insulin-like growth factors and their binding proteins. Author(s): Powell DR, Liu F, Baker BK, Hinzt RL, Kale A, Suwanichkul A, Durham SK. Source: Pediatric Nephrology (Berlin, Germany). 2000 July; 14(7): 579-83. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10912522&dopt=Abstract

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Effect of daily hormone therapy and alendronate use on bone mineral density in postmenopausal women. Author(s): Davas I, Altintas A, Yoldemir T, Varolan A, Yazgan A, Baksu B. Source: Fertility and Sterility. 2003 September; 80(3): 536-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12969694&dopt=Abstract

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Effect of growth hormone therapy in patients with Crohn disease. Author(s): Henker J. Source: Journal of Pediatric Gastroenterology and Nutrition. 2002 April; 34(4): 424-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11930104&dopt=Abstract

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Effect of growth hormone therapy on feeding problems and food intake in children with growth disorders. Author(s): Blissett J, Harris G, Kirk J. Source: Acta Paediatrica (Oslo, Norway : 1992). 2000 June; 89(6): 644-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10914955&dopt=Abstract

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Effect of growth hormone therapy on height in children with idiopathic short stature: a meta-analysis. Author(s): Finkelstein BS, Imperiale TF, Speroff T, Marrero U, Radcliffe DJ, Cuttler L. Source: Archives of Pediatrics & Adolescent Medicine. 2002 March; 156(3): 230-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11876666&dopt=Abstract

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Effect of long-term recombinant growth hormone therapy in children--the National Cooperative Growth Study, USA, 1985-1994. Author(s): Root AW, Kemp SF, Rundle AC, Dana K, Attie KM. Source: J Pediatr Endocrinol Metab. 1998; 11(3): 403-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11517956&dopt=Abstract

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Effect of postmenopausal hormone therapy on cardiovascular risk. Author(s): Rossouw JE. Source: Journal of Hypertension. 2002 May; 20 Suppl 2: S62-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12183856&dopt=Abstract

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Effect of postmenopausal hormone therapy on cognitive function: the Heart and Estrogen/progestin Replacement Study. Author(s): Grady D, Yaffe K, Kristof M, Lin F, Richards C, Barrett-Connor E. Source: The American Journal of Medicine. 2002 November; 113(7): 543-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12459399&dopt=Abstract

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Effect of postmenopausal hormone therapy on coronary heart disease events after percutaneous transluminal coronary angioplasty. Author(s): Khan MA, Hlatky MA, Liu MW, Lin F, Rogers WJ, Shlipak MG; HERS Investigators. Source: The American Journal of Cardiology. 2003 April 15; 91(8): 989-91, A7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12686345&dopt=Abstract

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Effect of short-term hormone therapy on oxidative stress and endothelial function in African American and Caucasian postmenopausal women. Author(s): Ke RW, Todd Pace D, Ahokas RA. Source: Fertility and Sterility. 2003 May; 79(5): 1118-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12738505&dopt=Abstract

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Effective growth hormone therapy in a growth hormone deficient patient with Duchenne muscular dystropy without evidence of acceleration of the dystrophic process. Author(s): Frank GR, Smith RE. Source: J Pediatr Endocrinol Metab. 2001 February; 14(2): 211-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11305801&dopt=Abstract

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Effects of acute hormone therapy on recurrent ischemia in postmenopausal women with unstable angina. Author(s): Schulman SP, Thiemann DR, Ouyang P, Chandra NC, Schulman DS, Reis SE, Terrin M, Forman S, de Albuquerque CP, Bahr RD, Townsend SN, Cosgriff R, Gerstenblith G. Source: Journal of the American College of Cardiology. 2002 January 16; 39(2): 231-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11788212&dopt=Abstract

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Effects of hormone therapy and alendronate on C-reactive protein, E-selectin, and sex hormone-binding globulin in osteoporotic women. Author(s): Ylikorkala O, Evio S, Valimaki M, Tiitinen A. Source: Fertility and Sterility. 2003 September; 80(3): 541-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12969695&dopt=Abstract

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Effects of long-term hormone therapy on cholinergic synaptic concentrations in healthy postmenopausal women. Author(s): Smith YR, Minoshima S, Kuhl DE, Zubieta JK. Source: The Journal of Clinical Endocrinology and Metabolism. 2001 February; 86(2): 679-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11158031&dopt=Abstract

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Effects of short-term recombinant human growth hormone therapy on plasma leptin concentrations in dialysis patients. Author(s): Iglesias P, Diez JJ, Fernandez-Reyes MJ, Bajo MA, Aguilera A, Mendez J, Codoceo R, Selgas R. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 2002 February; 17(2): 260-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11812876&dopt=Abstract

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Efficacy of growth hormone therapy for patients with skeletal dysplasia. Author(s): Kanazawa H, Tanaka H, Inoue M, Yamanaka Y, Namba N, Seino Y. Source: Journal of Bone and Mineral Metabolism. 2003; 21(5): 307-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12928832&dopt=Abstract

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Elevated serum Her-2/neu level predicts decreased response to hormone therapy in metastatic breast cancer. Author(s): Lipton A, Ali SM, Leitzel K, Demers L, Chinchilli V, Engle L, Harvey HA, Brady C, Nalin CM, Dugan M, Carney W, Allard J. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2002 March 15; 20(6): 1467-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11896093&dopt=Abstract

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Estrogen or no Estrogen. A Hormone Therapy Dilemma. Author(s): Youngkin EQ. Source: Awhonn Lifelines / Association of Women's Health, Obstetric and Neonatal Nurses. 2001 December-2002 January; 5(6): 96, 95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11778470&dopt=Abstract

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Evidence-based growth hormone therapy prediction models. Author(s): Hindmarsh PC, Cole TJ. Source: J Pediatr Endocrinol Metab. 2000; 13 Suppl 6: 1359-64. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11202210&dopt=Abstract

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Evidence-based practice in women's health: hormone therapy for women at menopause. Author(s): Rousseau ME. Source: Journal of Midwifery & Women's Health. 2001 May-June; 46(3): 167-80. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11480749&dopt=Abstract

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Expanded spectrum of recombinant human growth hormone therapy. Author(s): Henwood MJ, Grimberg A, Moshang T Jr. Source: Current Opinion in Pediatrics. 2002 August; 14(4): 437-42. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12130909&dopt=Abstract

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Experience with growth hormone therapy in Turner syndrome in a single centre: low total height gain, no further gains after puberty onset and unchanged body proportions. Author(s): Schweizer R, Ranke MB, Binder G, Herdach F, Zapadlo M, Grauer ML, Schwarze CP, Wollmann HA. Source: Hormone Research. 2000; 53(5): 228-38. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11150884&dopt=Abstract

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Expression of insulin target genes in skeletal muscle and adipose tissue in adult patients with growth hormone deficiency: effect of one year recombinant human growth hormone therapy. Author(s): Khalfallah Y, Sassolas G, Borson-Chazot F, Vega N, Vidal H. Source: The Journal of Endocrinology. 2001 November; 171(2): 285-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11691648&dopt=Abstract

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Failure of hormone therapy in prostate cancer involves systematic restoration of androgen responsive genes and activation of rapamycin sensitive signaling. Author(s): Mousses S, Wagner U, Chen Y, Kim JW, Bubendorf L, Bittner M, Pretlow T, Elkahloun AG, Trepel JB, Kallioniemi OP. Source: Oncogene. 2001 October 11; 20(46): 6718-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11709706&dopt=Abstract

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Fatigue in patients with prostate cancer receiving hormone therapy. Author(s): Stone P, Hardy J, Huddart R, A'Hern R, Richards M. Source: European Journal of Cancer (Oxford, England : 1990). 2000 June; 36(9): 1134-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10854947&dopt=Abstract

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Floating-Harbor syndrome in two unrelated girls: mild short stature in one patient and effective growth hormone therapy in the other. Author(s): Wieczorek D, Wusthof A, Harms E, Meinecke P. Source: American Journal of Medical Genetics. 2001 November 15; 104(1): 47-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11746027&dopt=Abstract

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For women on hormone therapy, other options may be safer. Author(s): Brink S. Source: U.S. News & World Report. 2000 February 7; 128(5): 58. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11184138&dopt=Abstract

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From in vitro fertilization (IVF) to menopause: physiologic hormone replacement adapted from donor egg IVF may be our best option for hormone therapy. Author(s): de Ziegler D, Meldrum DR. Source: Fertility and Sterility. 2003 September; 80(3): 485-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12969682&dopt=Abstract

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From presumed benefit to potential harm--hormone therapy and heart disease. Author(s): Herrington DM, Howard TD. Source: The New England Journal of Medicine. 2003 August 7; 349(6): 519-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12904515&dopt=Abstract

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Functional and morphologic evaluation of the nasal mucosa before and after hormone therapy in postmenopausal women with nasal symptoms. Author(s): Nappi C, Di Spiezio Sardo A, Guerra G, Bifulco G, Testa D, Di Carlo C. Source: Fertility and Sterility. 2003 September; 80(3): 669-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12969725&dopt=Abstract

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Glycemic effects of postmenopausal hormone therapy: the Heart and Estrogen/progestin Replacement Study. A randomized, double-blind, placebocontrolled trial. Author(s): Kanaya AM, Herrington D, Vittinghoff E, Lin F, Grady D, Bittner V, Cauley JA, Barrett-Connor E; Heart and Estrogen/progestin Replacement Study. Source: Annals of Internal Medicine. 2003 January 7; 138(1): 1-9. Summary for Patients In: http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12513038&dopt=Abstract

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Growth hormone therapy alone or in combination with gonadotropin-releasing hormone analog therapy to improve the height deficit in children with congenital adrenal hyperplasia. Author(s): Quintos JB, Vogiatzi MG, Harbison MD, New MI. Source: The Journal of Clinical Endocrinology and Metabolism. 2001 April; 86(4): 1511-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11297576&dopt=Abstract

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Growth hormone therapy and children with idiopathic short stature: a viable option? Author(s): Willhaus J. Source: Pediatric Nursing. 1999 November-December; 25(6): 662-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12024388&dopt=Abstract

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Growth hormone therapy and growth in children with Noonan's syndrome: results of 3 years' follow-up. Author(s): MacFarlane CE, Brown DC, Johnston LB, Patton MA, Dunger DB, Savage MO, McKenna WJ, Kelnar CJ. Source: The Journal of Clinical Endocrinology and Metabolism. 2001 May; 86(5): 1953-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11344190&dopt=Abstract

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Growth hormone therapy and its relationship to insulin resistance, glucose intolerance and diabetes mellitus: a review of recent evidence. Author(s): Jeffcoate W. Source: Drug Safety : an International Journal of Medical Toxicology and Drug Experience. 2002; 25(3): 199-212. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11945115&dopt=Abstract

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Growth hormone therapy and lipid profile in children on chronic peritoneal dialysis. Author(s): Jedrzejowski A, Panczyk-Tomaszewska M, Roszkowska-Blaim M, Lis D, Galazka B, Dyras P. Source: Pediatric Nephrology (Berlin, Germany). 2002 October; 17(10): 830-6. Epub 2002 August 16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12376812&dopt=Abstract

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Growth hormone therapy for adults: not ready for prime time? Author(s): Isley WL. Source: Annals of Internal Medicine. 2002 August 6; 137(3): 190-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12160367&dopt=Abstract

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Growth hormone therapy for hypopituitary adults: time for re-appraisal. Author(s): Barkan AL, Clemmons DR, Molitch ME, Stewart PM, Young WF Jr. Source: Trends in Endocrinology and Metabolism: Tem. 2000 August; 11(6): 238-45. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10878755&dopt=Abstract

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Growth hormone therapy for non-islet cell tumor hypoglycemia. Author(s): Silveira LF, Bouloux PM, MacColl GS, Camacho-Hubner C, Miraki-Moud F. Source: The American Journal of Medicine. 2002 August 15; 113(3): 255-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12208393&dopt=Abstract

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Growth hormone therapy for Prader-Willi and Down syndromes: a post-modern medical dilemma. Author(s): Lantos JD. Source: Growth Hormone & Igf Research : Official Journal of the Growth Hormone Research Society and the International Igf Research Society. 2000 April; 10 Suppl B: S934. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10984261&dopt=Abstract

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Growth hormone therapy for syndromic disorders. Author(s): Kelnar CJ. Source: Clinical Endocrinology. 2003 July; 59(1): 12-21. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12807497&dopt=Abstract

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Growth hormone therapy in achondroplasia. Author(s): Seino Y, Yamanaka Y, Shinohara M, Ikegami S, Koike M, Miyazawa M, Inoue M, Moriwake T, Tanaka H. Source: Hormone Research. 2000; 53 Suppl 3: 53-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10971105&dopt=Abstract

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Growth hormone therapy in adults. Author(s): Cummings DE, Merriam GR. Source: Annual Review of Medicine. 2003; 54: 513-33. Epub 2001 December 03. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12471175&dopt=Abstract

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Growth hormone therapy in adults. Author(s): Conceicao FL, Bojensen A, Jorgensen JO, Christiansen JS. Source: Frontiers in Neuroendocrinology. 2001 July; 22(3): 213-46. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11456469&dopt=Abstract

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Growth hormone therapy in adults: what case managers need to know. Author(s): Birmingham J. Source: The Case Manager. 2001 March-April; 12(2): 57-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11244404&dopt=Abstract

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Growth hormone therapy in childhood-onset growth hormone deficiency: adult anthropometric and psychological outcomes. Author(s): Sandberg DE, MacGillivray MH. Source: Endocrine. 2000 April; 12(2): 173-82. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10905377&dopt=Abstract

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Growth hormone therapy in children with growth hormone deficiency. Author(s): Hsu HH. Source: Acta Paediatr Taiwan. 2001 September-October; 42(5): 269-70. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11729701&dopt=Abstract

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Growth hormone therapy in children with idiopathic short stature. Author(s): Bryant J, Cave C, Milne R. Source: Archives of Pediatrics & Adolescent Medicine. 2002 September; 156(9): 946-7; Author Reply 947. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12197809&dopt=Abstract

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Growth hormone therapy in children with short stature: is bigger better or achievable? Author(s): Germak JA. Source: Indian J Pediatr. 1996 September-October; 63(5): 591-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10830027&dopt=Abstract

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Growth hormone therapy in chronic renal failure induces catch-up of head circumference. Author(s): Van Dyck M, Proesmans W. Source: Pediatric Nephrology (Berlin, Germany). 2001 August; 16(8): 631-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11519892&dopt=Abstract

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Growth hormone therapy in heart failure: where are we now? Author(s): Demers C, McKelvie RS. Source: Congestive Heart Failure (Greenwich, Conn.). 2003 March-April; 9(2): 84-90. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12671339&dopt=Abstract

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Growth hormone therapy in noonan syndrome. Author(s): Kelnar CJ. Source: Hormone Research. 2000; 53 Suppl 1: 77-81. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10895047&dopt=Abstract

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Growth hormone therapy in Noonan's syndrome: non-cardiomyopathic congenital heart disease does not adversely affect growth improvement. Author(s): Brown DC, Macfarlane CE, McKenna WJ, Patton MA, Dunger DB, Savage MO, Kelnar CJ. Source: J Pediatr Endocrinol Metab. 2002 June; 15(6): 851-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12099396&dopt=Abstract

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Growth hormone therapy in Prader-Willi syndrome. Author(s): Davies PS. Source: International Journal of Obesity and Related Metabolic Disorders : Journal of the International Association for the Study of Obesity. 2001 January; 25(1): 2-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11244451&dopt=Abstract

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Growth hormone therapy in the glucocorticosteroid-dependent child: metabolic and linear growth effects. Author(s): Mauras N. Source: Hormone Research. 2001; 56 Suppl 1: 13-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11786679&dopt=Abstract

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Growth hormone therapy in the Prader-Willi syndrome. Author(s): Paterson WF, Donaldson MD. Source: Archives of Disease in Childhood. 2003 April; 88(4): 283-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12651746&dopt=Abstract

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Growth hormone therapy in Turner syndrome. Author(s): Lee YJ. Source: Acta Paediatr Taiwan. 2000 November-December; 41(6): 292-3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11198933&dopt=Abstract

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Growth hormone therapy in young children with Down syndrome and a clinical comparison of Down and Prader-Willi syndromes. Author(s): Anneren G, Tuvemo T, Gustafsson J. Source: Growth Hormone & Igf Research : Official Journal of the Growth Hormone Research Society and the International Igf Research Society. 2000 April; 10 Suppl B: S8791. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10984260&dopt=Abstract

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Growth hormone therapy may increase fracture risk in a pubertal patient with osteogenesis imperfecta. Author(s): Noda H, Onishi H, Saitoh K, Nakajima H. Source: J Pediatr Endocrinol Metab. 2002 February; 15(2): 217-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11874188&dopt=Abstract

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Growth hormone therapy of Turner syndrome: the impact of age of estrogen replacement on final height. Genentech, Inc., Collaborative Study Group. Author(s): Chernausek SD, Attie KM, Cara JF, Rosenfeld RG, Frane J. Source: The Journal of Clinical Endocrinology and Metabolism. 2000 July; 85(7): 2439-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10902791&dopt=Abstract

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Growth hormone therapy. Author(s): Wit JM. Source: Best Practice & Research. Clinical Endocrinology & Metabolism. 2002 September; 16(3): 483-503. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12464230&dopt=Abstract

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Growth hormone therapy. Author(s): Dash RJ, Muralidharan R, Talwar V. Source: J Assoc Physicians India. 1999 April; 47(4): 417-25. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10778529&dopt=Abstract

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Growth hormone therapy. Determining appropriate use. Author(s): Miller K. Source: Adv Nurse Pract. 2002 March; 10(3): 89-92, 95-6. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12418342&dopt=Abstract

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Growth over 10 years following a 1-year trial of growth hormone therapy. Author(s): Rees L, Ward G, Rigden SP. Source: Pediatric Nephrology (Berlin, Germany). 2000 April; 14(4): 309-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10775075&dopt=Abstract

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Height responses in complete idiopathic growth hormone deficient children less than three years of age during growth hormone therapy. Executive Committee of the International Cooperative Growth Study in Japan. Author(s): Hirano T, Takano K, Tanaka T, Hanew K, Igarashi Y, Nishi Y, Fujieda K, Tachibana K, Yokoya S. Source: Endocrine Journal. 1999 March; 46 Suppl: S1-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12058738&dopt=Abstract

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Hepatic adenoma associated with recombinant human growth hormone therapy in a patient with Turner's syndrome. Author(s): Espat J, Chamberlain RS, Sklar C, Blumgart LH. Source: Digestive Surgery. 2000; 17(6): 640-643. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11155014&dopt=Abstract

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HER-2 amplification impedes the antiproliferative effects of hormone therapy in estrogen receptor-positive primary breast cancer. Author(s): Dowsett M, Harper-Wynne C, Boeddinghaus I, Salter J, Hills M, Dixon M, Ebbs S, Gui G, Sacks N, Smith I. Source: Cancer Research. 2001 December 1; 61(23): 8452-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11731427&dopt=Abstract

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Her-2/neu expression in prostate cancer: high level of expression associated with exposure to hormone therapy and androgen independent disease. Author(s): Shi Y, Brands FH, Chatterjee S, Feng AC, Groshen S, Schewe J, Lieskovsky G, Cote RJ. Source: The Journal of Urology. 2001 October; 166(4): 1514-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11547123&dopt=Abstract

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Heterozygous mutation in the WSXWS equivalaent motif of the growth hormone receptor in a child with poor response to growth hormone therapy. Author(s): Tauber MT, Porra V, Dastot F, Molinas C, Amselem S, Cholin S, Rochiccioli P, Bieth E. Source: Growth Hormone & Igf Research : Official Journal of the Growth Hormone Research Society and the International Igf Research Society. 1998 June; 8(3): 211-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10984309&dopt=Abstract

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Hormone therapy and breast cancer. Author(s): Zimmerman VL, Smeltzer SC. Source: Clin Excell Nurse Pract. 2000 January; 4(1): 30-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11858293&dopt=Abstract

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Hormone therapy and heart disease after the menopause. Author(s): Skegg DC. Source: Lancet. 2001 October 13; 358(9289): 1196-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11675050&dopt=Abstract

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Hormone therapy and heart disease. Author(s): Stevenson JC. Source: Lancet. 2002 March 2; 359(9308): 795-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11888613&dopt=Abstract

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Hormone therapy and in-hospital survival after myocardial infarction in postmenopausal women. Author(s): Shlipak MG, Angeja BG, Go AS, Frederick PD, Canto JG, Grady D. Source: Circulation. 2001 November 6; 104(19): 2300-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11696469&dopt=Abstract

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Hormone therapy and risk for venous thromboembolism: comments and correction. Author(s): Goldstein MR. Source: Annals of Internal Medicine. 2001 January 2; 134(1): 81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11187427&dopt=Abstract

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Hormone therapy and risk for venous thromboembolism: comments and correction. Author(s): Waitkevicz HJ, Axelrod D. Source: Annals of Internal Medicine. 2001 January 2; 134(1): 80-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11187425&dopt=Abstract

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Hormone therapy and risk for venous thromboembolism: comments and corrections. Author(s): Peverill R. Source: Annals of Internal Medicine. 2001 January 2; 134(1): 80; Author Reply 81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11187426&dopt=Abstract

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Hormone therapy and risk of Alzheimer disease: a critical time. Author(s): Resnick SM, Henderson VW. Source: Jama : the Journal of the American Medical Association. 2002 November 6; 288(17): 2170-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12413378&dopt=Abstract

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Hormone therapy and smoking. Author(s): Andrews C. Source: J Gend Specif Med. 2000 July-August; 3(5): 66-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11253259&dopt=Abstract

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Hormone therapy and the brain: deja vu all over again? Author(s): Yaffe K. Source: Jama : the Journal of the American Medical Association. 2003 May 28; 289(20): 2717-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12771119&dopt=Abstract

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Hormone therapy and the cardiovascular system. Author(s): Pines A. Source: Maturitas. 2002 August 30; 43 Suppl 1: S3-10. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12361883&dopt=Abstract

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Hormone therapy and the progression of coronary-artery atherosclerosis in postmenopausal women. Author(s): Hodis HN, Mack WJ, Azen SP, Lobo RA, Shoupe D, Mahrer PR, Faxon DP, Cashin-Hemphill L, Sanmarco ME, French WJ, Shook TL, Gaarder TD, Mehra AO, Rabbani R, Sevanian A, Shil AB, Torres M, Vogelbach KH, Selzer RH; Women's Estrogen-Progestin Lipid-Lowering Hormone Atherosclerosis Regression Trial Research Group. Source: The New England Journal of Medicine. 2003 August 7; 349(6): 535-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12904518&dopt=Abstract

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Hormone therapy and the risk of stroke after acute myocardial infarction in postmenopausal women. Author(s): Angeja BG, Shlipak MG, Go AS, Johnston SC, Frederick PD, Canto JG, Barron HV, Grady D; National Registry of Myocardial Infarction 3 Investigators. Source: Journal of the American College of Cardiology. 2001 November 1; 38(5): 1297301. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11691498&dopt=Abstract

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Hormone therapy and venous thromboembolism. Author(s): Peverill RE. Source: Best Practice & Research. Clinical Endocrinology & Metabolism. 2003 March; 17(1): 149-64. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12763518&dopt=Abstract

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Hormone therapy for locally advanced prostate cancer. Author(s): Fowler JE Jr, Bigler SA, White PC, Duncan WL. Source: The Journal of Urology. 2002 August; 168(2): 546-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12131306&dopt=Abstract

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Hormone therapy for patients with prostate carcinoma. Author(s): Klotz L. Source: Cancer. 2000 June 15; 88(12 Suppl): 3009-14. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10898345&dopt=Abstract

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Hormone therapy in advanced prostate cancer. Author(s): Forster TH, Stoffel F, Gasser TC. Source: Front Radiat Ther Oncol. 2002; 36: 49-65. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11842755&dopt=Abstract

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Hormone therapy in epithelial ovarian cancer. Author(s): Makar AP. Source: Endocrine-Related Cancer. 2000 June; 7(2): 85-93. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10903526&dopt=Abstract

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Hormone therapy in men and risk of cardiac allograft rejection. Author(s): Schofield RS, Hill JA, McGinn CJ, Aranda JM. Source: The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. 2002 April; 21(4): 493-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11927227&dopt=Abstract

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Hormone therapy in menopause: the plot thickens. Author(s): Good AE. Source: Minn Med. 2003 January; 86(1): 32-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12585557&dopt=Abstract

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Hormone therapy of prostate cancer: is there a role for antiandrogen monotherapy? Author(s): Boccardo F. Source: Critical Reviews in Oncology/Hematology. 2000 August; 35(2): 121-32. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10936469&dopt=Abstract

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Hormone therapy revisited: data from the population, treatment for the patient. Author(s): Hughes KS, Roche CA. Source: Menopause (New York, N.Y.). 2003 July-August; 10(4): 269-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12851507&dopt=Abstract

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Hormone therapy. Author(s): Gambacciani M, Genazzani AR. Source: Menopause (New York, N.Y.). 2003 May-June; 10(3): 266-7; Author Reply 267. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12792300&dopt=Abstract

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Hormone therapy: continuing discussion and debate. Author(s): Apgar BS, Weismiller DG. Source: American Family Physician. 2003 April 1; 67(7): 1444, 1446, 1449. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12722847&dopt=Abstract

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Hormone therapy: evolving concepts. Author(s): Hendrix SL. Source: Current Opinion in Rheumatology. 2003 July; 15(4): 464-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12819476&dopt=Abstract

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Hormone therapy: the Women's Health Initiative has caused confusion and concern. Author(s): Reid RL. Source: Fertility and Sterility. 2003 September; 80(3): 491-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12969684&dopt=Abstract

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Iatrogenic Creutzfeldt-Jakob disease following human growth hormone therapy: case report. Author(s): Caboclo LO, Huang N, Lepski GA, Livramento JA, Buchpiguel CA, Porto CS, Nitrini R. Source: Arquivos De Neuro-Psiquiatria. 2002 June; 60(2-B): 458-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12131950&dopt=Abstract

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Immune system in adults with childhood-onset growth hormone deficiency: effect of growth hormone therapy. Author(s): Lebl J, Sediva A, Snajderova M, Pruhova S, Rakosnikova V. Source: Endocrine Regulations. 2000 December; 34(4): 169-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11135489&dopt=Abstract

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Immunotherapy (recombinant interleukin 2), hormone therapy (medroxyprogesterone acetate) and antioxidant agents as combined maintenance treatment of responders to previous chemotherapy. Author(s): Mantovani G, Maccio A, Madeddu C, Massa E, Mudu MC, Mulas C, Gramignano G, Massidda S, Murgia V, Lusso MR, Mura L. Source: International Journal of Oncology. 2001 February; 18(2): 383-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11172608&dopt=Abstract

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Influence of adjuvant hormone therapy and chemotherapy on the immune system analysed in the bone marrow of patients with breast cancer. Author(s): Solomayer EF, Feuerer M, Bai L, Umansky V, Beckhove P, Meyberg GC, Bastert G, Schirrmacher V, Diel IJ. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 2003 January; 9(1): 174-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12538466&dopt=Abstract

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Influence of growth hormone therapy on pituitary and lumbar spine astrocytomas. A clinical observation. Author(s): Mohn A, di Ricco L, de Santis A, Tartaro A, Capanna R, Chiarelli F. Source: Hormone Research. 2003; 59(3): 156-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12637796&dopt=Abstract

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Interaction of hemostatic genetics with hormone therapy: new insights to explain arterial thrombosis in postmenopausal women. Author(s): Braunstein JB, Kershner DW, Bray P, Gerstenblith G, Schulman SP, Post WS, Blumenthal RS. Source: Chest. 2002 March; 121(3): 906-20. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11888977&dopt=Abstract

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Intermittent hormone therapy: its potential in early prostate cancer and intraepithelial neoplasia. Author(s): Oliver RT. Source: Gan to Kagaku Ryoho. 2000 May; 27 Suppl 2: 399-404. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10895186&dopt=Abstract

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Intra-arterial liver chemotherapy and hormone therapy in malignant insulinoma: case report and review of the literature. Author(s): Moscetti L, Saltarelli R, Giuliani R, Fornarini G, Bezzi M, Cortesi E. Source: Tumori. 2000 November-December; 86(6): 475-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11218190&dopt=Abstract

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Is bio-identical hormone therapy fact or fairy tale? Author(s): Francisco L. Source: The Nurse Practitioner. 2003 July; 28(7 Pt 1): 39-44, Table of Contents. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12861094&dopt=Abstract

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Is hormone therapy still an option for the management of osteoporosis? Author(s): MacLennan A, Sturdee D. Source: Climacteric : the Journal of the International Menopause Society. 2003 June; 6(2): 89-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12848151&dopt=Abstract

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Leptin in postmenopausal women: influence of hormone therapy, insulin, and fat distribution. Author(s): Gower BA, Nagy TR, Goran MI, Smith A, Kent E. Source: The Journal of Clinical Endocrinology and Metabolism. 2000 May; 85(5): 1770-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10843150&dopt=Abstract

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Lipids, blood pressure and bone metabolism after growth hormone therapy in elderly hemodialysis patients. Author(s): Viidas U, Johannsson G, Mattson-Hulten L, Ahlmen J. Source: Journal of Nephrology. 2003 March-April; 16(2): 231-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12768070&dopt=Abstract

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Locally advanced primary breast cancer: medium-term results of a randomised trial of multimodal therapy versus initial hormone therapy. Author(s): Tan SM, Cheung KL, Willsher PC, Blamey RW, Chan SY, Robertson JF. Source: European Journal of Cancer (Oxford, England : 1990). 2001 December; 37(18): 2331-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11720825&dopt=Abstract

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Longitudinal follow-up study of 11 patients with pulmonary lymphangioleiomyomatosis: diverse clinical courses of LAM allow some patients to be treated without anti-hormone therapy. Author(s): Seyama K, Kira S, Takahashi H, Ohnishi M, Kodama Y, Dambara T, Kobayashi J, Kitamura S, Fukuchi Y. Source: Respirology (Carlton, Vic.). 2001 December; 6(4): 331-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11844125&dopt=Abstract

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Long-term effects of growth hormone therapy on bone mineral density, body composition, and serum lipid levels in growth hormone deficient children: a 6-year follow-up study. Author(s): van der Sluis IM, Boot AM, Hop WC, De Rijke YB, Krenning EP, de Muinck Keizer-Schrama SM. Source: Hormone Research. 2002; 58(5): 207-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12401939&dopt=Abstract

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Long-term neoadjuvant hormone therapy prior to radical prostatectomy: evaluation of risk for biochemical recurrence at 5-year follow-up. Author(s): Gleave ME, La Bianca SE, Goldenberg SL, Jones EC, Bruchovsky N, Sullivan LD. Source: Urology. 2000 August 1; 56(2): 289-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10925096&dopt=Abstract

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Long-term results of growth hormone therapy in Turner syndrome. Author(s): Bramswig JH. Source: Endocrine. 2001 June; 15(1): 5-13. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11572325&dopt=Abstract

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Long-term results with growth hormone therapy in idiopathic hypopituitarism. Author(s): Bernasconi S, Arrigo T, Wasniewsk M, Ghizzoni L, Ruggeri C, Di Pasquale G, Vottero A, De Luca F. Source: Hormone Research. 2000; 53 Suppl 1: 55-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10895044&dopt=Abstract

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Low dose 25 mg oestradiol implants and 1 mg norethisterone as continuous combined hormone therapy: a prospective study. Author(s): Panay N, Zamblera D, Sands R, Jones J, Alaghband-Zadeh J, Studd JW. Source: Bjog : an International Journal of Obstetrics and Gynaecology. 2002 August; 109(8): 958-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12197380&dopt=Abstract

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Low-dose hormone therapy and carbohydrate metabolism. Author(s): Li C, Samsioe G, Borgfeldt C, Bendahl PO, Wilawan K, Aberg A. Source: Fertility and Sterility. 2003 March; 79(3): 550-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12620438&dopt=Abstract

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Low-dose hormone therapy for postmenopausal women. Author(s): Archer DF. Source: Clinical Obstetrics and Gynecology. 2003 June; 46(2): 317-24. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12808382&dopt=Abstract

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Menopausal hormone therapy: a paradigm shift? Author(s): Liu JH. Source: Fertility and Sterility. 2003 September; 80(3): 494-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12969685&dopt=Abstract

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Menopausal hormone therapy: summary of a scientific workshop. Author(s): Kirschstein R. Source: Annals of Internal Medicine. 2003 February 18; 138(4): 361-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12585848&dopt=Abstract

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Menopausal symptoms in older women and the effects of treatment with hormone therapy. Author(s): Barnabei VM, Grady D, Stovall DW, Cauley JA, Lin F, Stuenkel CA, Stefanick ML, Pickar JH. Source: Obstetrics and Gynecology. 2002 December; 100(6): 1209-18. Erratum In: Obstet Gynecol. 2003 March; 101(3): 619. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12468165&dopt=Abstract

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Midlife women making hormone therapy decisions. Author(s): MacLaren A, Woods NF. Source: Women's Health Issues : Official Publication of the Jacobs Institute of Women's Health. 2001 May-June; 11(3): 216-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11336862&dopt=Abstract

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M-mode echocardiographic evaluation of systolic function, LV volume and mass in children on growth hormone therapy. Author(s): Stamoyannou L, Georgacopoulos D, Trapali C, Neou P, Bartsocas CS, Margetakis A. Source: J Pediatr Endocrinol Metab. 2000 February; 13(2): 157-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10711660&dopt=Abstract

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Neoadjuvant and adjuvant hormone therapy for prostate cancer. Author(s): Zlotta AR, Schulman CC. Source: World Journal of Urology. 2000 June; 18(3): 179-82. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10926081&dopt=Abstract

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Neoadjuvant hormone therapy and external beam radiation for localized prostate cancer: Vancouver Island Cancer Centre experience. Author(s): Ludgate CM, Lim JT, Wilson AG, Alexander AS, Wilson KS. Source: Can J Urol. 2000 February; 7(1): 937-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11121249&dopt=Abstract

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Neoadjuvant hormone therapy and radical prostatectomy: the jury is still out. Author(s): Van Poppel H. Source: European Urology. 2001; 39 Suppl 1: 10-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11114595&dopt=Abstract

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Neoadjuvant hormone therapy and radical radiotherapy for localized prostate cancer: poorer biochemical outcome using flutamide alone. Author(s): Wilson KS, Ludgate CM, Wilson AG, Alexander AS. Source: Can J Urol. 2000 October; 7(5): 1099-103. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11114872&dopt=Abstract

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Neoadjuvant hormone therapy before radical prostatectomy does not improve disease-specific survival. Author(s): Steiner MS. Source: Curr Urol Rep. 2000 May; 1(1): 7-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12084334&dopt=Abstract

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Neoadjuvant hormone therapy before salvage radiotherapy for an increasing postradical prostatectomy serum prostate specific antigen level. Author(s): Tiguert R, Rigaud J, Lacombe L, Laverdiere J, Fradet Y. Source: The Journal of Urology. 2003 August; 170(2 Pt 1): 447-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12853796&dopt=Abstract

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Neoadjuvant hormone therapy: the Canadian trials. Author(s): Klotz L, Gleave M, Goldenberg SL. Source: Molecular Urology. 2000 Fall; 4(3): 233-7; Discussion 239. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11062379&dopt=Abstract

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New advice for women patients about hormone therapy and the heart. Author(s): Mitka M. Source: Jama : the Journal of the American Medical Association. 2001 August 22-29; 286(8): 907. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11509036&dopt=Abstract

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New directions in hormone therapy for metastatic breast cancer. Author(s): Namer M. Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 2002; 13 Suppl 4: 69-72. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12401669&dopt=Abstract

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New markers for cardiovascular disease risk in women: impact of endogenous estrogen status and exogenous postmenopausal hormone therapy. Author(s): Davison S, Davis SR. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 June; 88(6): 2470-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12788842&dopt=Abstract

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New paradigms for growth hormone therapy in children. Author(s): Wetterau L, Cohen P. Source: Hormone Research. 2000; 53 Suppl 3: 31-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10971101&dopt=Abstract

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New trends in prostatic cancer research. Hormone therapy in localized carcinoma of the prostate. Author(s): Perez CA. Source: Rays. 2000 July-September; 25(3): 345-51. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11367900&dopt=Abstract

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NIH conference addresses hormone therapy issues. Author(s): Traynor K. Source: American Journal of Health-System Pharmacy : Ajhp : Official Journal of the American Society of Health-System Pharmacists. 2002 December 1; 59(23): 2264, 2273. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12489361&dopt=Abstract

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Nilutamide as second line hormone therapy for prostate cancer after androgen ablation fails. Author(s): Kassouf W, Tanguay S, Aprikian AG. Source: The Journal of Urology. 2003 May; 169(5): 1742-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12686822&dopt=Abstract

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Noncardiovascular disease outcomes during 6.8 years of hormone therapy: Heart and Estrogen/progestin Replacement Study follow-up (HERS II). Author(s): Hulley S, Furberg C, Barrett-Connor E, Cauley J, Grady D, Haskell W, Knopp R, Lowery M, Satterfield S, Schrott H, Vittinghoff E, Hunninghake D; HERS Research Group. Source: Jama : the Journal of the American Medical Association. 2002 July 3; 288(1): 5866. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12090863&dopt=Abstract

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One-year growth hormone therapy improves granulocyte function without major effects on nutritional and anthropometric parameters in malnourished hemodialysis patients. Author(s): Kotzmann H, Schmidt A, Lercher P, Schuster E, Geyer G, Frisch H, Horl WH, Mayer G, Luger A. Source: Nephron. Clinical Practice [electronic Resource]. 2003; 93(2): C75-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12616034&dopt=Abstract

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Osteocalcin gene HindIII C/T polymorphism is a biomarker for prostate cancer and responsiveness to hormone therapy. Author(s): Wu HC, Lin CC, Chen WC, Chen HY, Tsai FJ. Source: European Urology. 2003 February; 43(2): 197-200. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12565780&dopt=Abstract

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Outcome of growth hormone therapy in children with growth hormone deficiency showing an inadequate response to growth hormone-releasing hormone. Author(s): Saenger P, Pescovitz OH, Bercu BB, Murray FT, Landy H, Brentzel J, O'Dea L, Hanson B, Howard C, Reiter EO; Geref International Study Group. Source: Endocrine. 2001 June; 15(1): 51-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11572326&dopt=Abstract

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Parathyroid hormone added to established hormone therapy: effects on vertebral fracture and maintenance of bone mass after parathyroid hormone withdrawal. Author(s): Cosman F, Nieves J, Woelfert L, Formica C, Gordon S, Shen V, Lindsay R. Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. 2001 May; 16(5): 925-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11341338&dopt=Abstract

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Patient communication in hormone therapy. Author(s): Schnare SM. Source: Int J Fertil Womens Med. 2001 January-February; 46(1): 24-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11294617&dopt=Abstract

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Persistent osteopenia in ballet dancers with amenorrhea and delayed menarche despite hormone therapy: a longitudinal study. Author(s): Warren MP, Brooks-Gunn J, Fox RP, Holderness CC, Hyle EP, Hamilton WG, Hamilton L. Source: Fertility and Sterility. 2003 August; 80(2): 398-404. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12909505&dopt=Abstract

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Postmenopausal hormone therapy and cardiovascular disease. Author(s): Otto C, Parhofer K. Source: Annals of Internal Medicine. 2001 December 18; 135(12): 1093-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11747399&dopt=Abstract

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Postmenopausal hormone therapy and cardiovascular disease. Author(s): Kessler KM. Source: Annals of Internal Medicine. 2001 December 18; 135(12): 1092-3; Author Reply 1093-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11747398&dopt=Abstract

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Postmenopausal hormone therapy and change in mammographic density. Author(s): Greendale GA, Reboussin BA, Slone S, Wasilauskas C, Pike MC, Ursin G. Source: Journal of the National Cancer Institute. 2003 January 1; 95(1): 30-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12509398&dopt=Abstract

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Postmenopausal hormone therapy and cognitive function in healthy older women. Author(s): Grodstein F, Chen J, Pollen DA, Albert MS, Wilson RS, Folstein MF, Evans DA, Stampfer MJ. Source: Journal of the American Geriatrics Society. 2000 July; 48(7): 746-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10894312&dopt=Abstract

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Post-menopausal hormone therapy and concentrations of protein C and antithrombin in elderly women. Author(s): Cushman M, Psaty BM, Meilahn EN, Dobs AS, Kuller LH. Source: British Journal of Haematology. 2001 July; 114(1): 162-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11472362&dopt=Abstract

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Postmenopausal hormone therapy and coronary heart disease: clinical implications of recent randomized trial results. Author(s): Speroff L. Source: Maturitas. 2000 May 29; 35(2): 91-7; Discussion 99-105. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10924834&dopt=Abstract

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Postmenopausal hormone therapy and primary prevention of cardiovascular disease - Nurses' health study 20-year follow-up. Author(s): Speroff L. Source: Maturitas. 2001 May 30; 38(3): 221-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11358636&dopt=Abstract

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Postmenopausal hormone therapy and quality of life: no cause for celebration. Author(s): Rexrode KM, Manson JE. Source: Jama : the Journal of the American Medical Association. 2002 February 6; 287(5): 641-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11829704&dopt=Abstract

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Postmenopausal hormone therapy and risk of breast cancer by histologic type (United States). Author(s): Newcomer LM, Newcomb PA, Potter JD, Yasui Y, Trentham-Dietz A, Storer BE, Longnecker MP, Baron JA, Daling JR. Source: Cancer Causes & Control : Ccc. 2003 April; 14(3): 225-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12814201&dopt=Abstract

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Postmenopausal hormone therapy and risk of stroke: The Heart and Estrogenprogestin Replacement Study (HERS). Author(s): Simon JA, Hsia J, Cauley JA, Richards C, Harris F, Fong J, Barrett-Connor E, Hulley SB. Source: Circulation. 2001 February 6; 103(5): 638-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11156873&dopt=Abstract

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Postmenopausal hormone therapy and the risk of cardiovascular disease: the epidemiologic evidence. Author(s): Hu FB, Grodstein F. Source: The American Journal of Cardiology. 2002 July 3; 90(1A): 26F-29F. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12106637&dopt=Abstract

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Postmenopausal hormone therapy for prevention of fractures: how good is the evidence? Author(s): Grady D, Cummings SR. Source: Jama : the Journal of the American Medical Association. 2001 June 13; 285(22): 2909-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11401615&dopt=Abstract

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Postmenopausal hormone therapy in the aftermath of the WHI. What patients need to know. Author(s): Cyr MG. Source: Postgraduate Medicine. 2003 March; 113(3): 15-8, 20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12647471&dopt=Abstract

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Postmenopausal hormone therapy increases risk for venous thromboembolic disease. The Heart and Estrogen/progestin Replacement Study. Author(s): Grady D, Wenger NK, Herrington D, Khan S, Furberg C, Hunninghake D, Vittinghoff E, Hulley S. Source: Annals of Internal Medicine. 2000 May 2; 132(9): 689-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10787361&dopt=Abstract

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Postmenopausal hormone therapy offers no protection against heart attacks. Author(s): American Medical Association. Source: Ginecologia Y Obstetricia De Mexico. 2002 August; 70: 404-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12448045&dopt=Abstract

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Postmenopausal hormone therapy. Author(s): Krieger N. Source: The New England Journal of Medicine. 2003 June 5; 348(23): 2363-4; Author Reply 2363-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12789008&dopt=Abstract

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Postmenopausal hormone therapy: a reversal of fortune. Author(s): Michels KB, Manson JE. Source: Circulation. 2003 April 15; 107(14): 1830-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12695280&dopt=Abstract

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Postmenopausal hormone therapy: have HERS2 and WHI given us any new information? Author(s): Fylstra DL. Source: J S C Med Assoc. 2002 December; 98(8): 299-304. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12532655&dopt=Abstract

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Postmenopausal hormone therapy: less favourable risk-benefit ratios in healthy Dutch women. Author(s): Moerman CJ, Van Hout BA, Bonneux L, Witteman JC. Source: Journal of Internal Medicine. 2000 August; 248(2): 143-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10947893&dopt=Abstract

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Premature thelarche in girls after growth hormone therapy. Author(s): Carvalho LR, Mimura LY, Arnhold IJ, Mendonca BB. Source: The Journal of Pediatrics. 2001 March; 138(3): 448-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11241065&dopt=Abstract

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Prevention of growth deceleration after withdrawal of growth hormone therapy in idiopathic short stature. Author(s): Lampit M, Hochberg Z. Source: The Journal of Clinical Endocrinology and Metabolism. 2002 August; 87(8): 3573-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12161476&dopt=Abstract

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Prognostic significance of the nadir prostate specific antigen level after hormone therapy for prostate cancer. Author(s): Kwak C, Jeong SJ, Park MS, Lee E, Lee SE. Source: The Journal of Urology. 2002 September; 168(3): 995-1000. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12187207&dopt=Abstract

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Pros and cons. Hormone therapy can do wonders for women, but a new cancer study underscores the risks. Author(s): Nash JM. Source: Time. 2000 February 7; 155(5): 68-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10787970&dopt=Abstract

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Prostate cancer DNA ploidy and response to salvage hormone therapy after radiotherapy with or without short-term total androgen blockade: an analysis of RTOG 8610. Author(s): Pollack A, Grignon DJ, Heydon KH, Hammond EH, Lawton CA, Mesic JB, Fu KK, Porter AT, Abrams RA, Shipley WU. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 April 1; 21(7): 1238-48. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12663710&dopt=Abstract

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Psychosocial adaptation to short stature - an indication for growth hormone therapy? Author(s): Wygold T. Source: Hormone Research. 2002; 58 Suppl 3: 20-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12435891&dopt=Abstract

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Pycnodysostosis: clinical, radiologic, and endocrine evaluation and linear growth after growth hormone therapy. Author(s): Soliman AT, Ramadan MA, Sherif A, Aziz Bedair ES, Rizk MM. Source: Metabolism: Clinical and Experimental. 2001 August; 50(8): 905-11. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11474477&dopt=Abstract

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Quality of life and hormone therapy in women before and after menopause. Author(s): Ekstrom H, Hovelius B. Source: Scandinavian Journal of Primary Health Care. 2000 June; 18(2): 115-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10944068&dopt=Abstract

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Quality-of-life and depressive symptoms in postmenopausal women after receiving hormone therapy: results from the Heart and Estrogen/Progestin Replacement Study (HERS) trial. Author(s): Hlatky MA, Boothroyd D, Vittinghoff E, Sharp P, Whooley MA; Heart and Estrogen/Progestin Replacement Study (HERS) Research Group. Source: Jama : the Journal of the American Medical Association. 2002 February 6; 287(5): 591-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11829697&dopt=Abstract

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Questions about hormone therapy remain puzzling. Author(s): Voelker R. Source: Jama : the Journal of the American Medical Association. 2002 November 20; 288(19): 2395-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12435239&dopt=Abstract

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Randomized trials in early prostate cancer. II: hormone therapy and radiotherapy for locally advanced disease: a question is still unanswered. MRC PR07 Trial Management Group. Author(s): Mason MD, Brewster S, Moffat LE, Kirkbride P, Cowan RA, Malone P, Sydes M, Parmar MK. Source: Clin Oncol (R Coll Radiol). 2000; 12(4): 215-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11005685&dopt=Abstract

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Recombinant human growth hormone therapy in adult dialysis patients. Author(s): Iglesias P, Diez JJ. Source: Int J Artif Organs. 2000 December; 23(12): 802-4. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11197738&dopt=Abstract

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Recombinant human growth hormone therapy in autosomal recessive polycystic kidney disease. Author(s): Lilova M, Kaplan BS, Meyers KE. Source: Pediatric Nephrology (Berlin, Germany). 2003 January; 18(1): 57-61. Epub 2002 November 26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12488992&dopt=Abstract

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Reduced insulin sensitivity during growth hormone therapy for short children born small for gestational age. Author(s): Cutfield WS, Jackson WE, Jefferies C, Robinson EM, Breier BH, Richards GE, Hofman PL. Source: The Journal of Pediatrics. 2003 February; 142(2): 113-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12584529&dopt=Abstract

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Relationship between long durations and different regimens of hormone therapy and risk of breast cancer. Author(s): Li CI, Malone KE, Porter PL, Weiss NS, Tang MT, Cushing-Haugen KL, Daling JR. Source: Jama : the Journal of the American Medical Association. 2003 June 25; 289(24): 3254-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12824206&dopt=Abstract

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Response to comments on 'A prospective, observational study of postmenopausal hormone therapy and primary prevention of cardiovascular disease'. Author(s): Grodstein F. Source: Maturitas. 2001 May 30; 38(3): 239-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11358641&dopt=Abstract

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Responses of bone turnover markers and bone mineral density to growth hormone therapy in children with isolated growth hormone deficiency and multiple pituitary hormone deficiencies. Author(s): Kandemir N, Gonc EN, Yordam N. Source: J Pediatr Endocrinol Metab. 2002 June; 15(6): 809-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12099391&dopt=Abstract

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Resumption of growth after methionyl-free human growth hormone therapy in a patient with neutralizing antibodies to methionyl human growth hormone. Author(s): Pitukcheewanont P, Schwarzbach L, Kaufman FR. Source: J Pediatr Endocrinol Metab. 2002 May; 15(5): 653-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12014526&dopt=Abstract

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Rethinking postmenopausal hormone therapy. Author(s): Solomon CG, Dluhy RG. Source: The New England Journal of Medicine. 2003 February 13; 348(7): 579-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12584364&dopt=Abstract

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Rheumatic manifestations of primary hyperparathyroidism and parathyroid hormone therapy. Author(s): Rubin MR, Silverberg SJ. Source: Curr Rheumatol Rep. 2002 April; 4(2): 179-85. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11890884&dopt=Abstract

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Risk of recurrent coronary events in relation to use and recent initiation of postmenopausal hormone therapy. Author(s): Heckbert SR, Kaplan RC, Weiss NS, Psaty BM, Lin D, Furberg CD, Starr JR, Anderson GD, LaCroix AZ. Source: Archives of Internal Medicine. 2001 July 23; 161(14): 1709-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11485503&dopt=Abstract

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Role of insulin-like growth factor monitoring in optimizing growth hormone therapy. Author(s): Wetterau L, Cohen P. Source: J Pediatr Endocrinol Metab. 2000; 13 Suppl 6: 1371-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11202212&dopt=Abstract

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Role of progestogen in hormone therapy for postmenopausal women: position statement of The North American Menopause Society. Author(s): North American Menopause Society. Source: Menopause (New York, N.Y.). 2003 March-April; 10(2): 113-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12627037&dopt=Abstract

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Rotational 3D-conformal radiation therapy (conformation therapy) combined with hormone therapy for the treatment of stage B2/C prostate cancer in Japanese men. Author(s): Karasawa K, Kaizu T, Niibe Y, Igaki H, Shinohara M, Tanaka Y, Matsuda T. Source: International Journal of Radiation Oncology, Biology, Physics. 2003 May 1; 56(1): 208-12. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12694840&dopt=Abstract

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Safety issues in children and adolescents during growth hormone therapy--a review. Author(s): Clayton PE, Cowell CT. Source: Growth Hormone & Igf Research : Official Journal of the Growth Hormone Research Society and the International Igf Research Society. 2000 December; 10(6): 30617. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11161961&dopt=Abstract

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Self-administered questionnaire compared with a personal diary for assessment of current use of hormone therapy: an analysis of 16,060 women. Author(s): Merlo J, Berglund G, Wirfalt E, Gullberg B, Hedblad B, Manjer J, Hovelius B, Janzon L, Hanson BS, Ostergren PO. Source: American Journal of Epidemiology. 2000 October 15; 152(8): 788-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11052558&dopt=Abstract

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Short stature in Noonan syndrome: response to growth hormone therapy. Author(s): Kirk JM, Betts PR, Butler GE, Donaldson MD, Dunger DB, Johnston DI, Kelnar CJ, Price DA, Wilton P, Group tU. Source: Archives of Disease in Childhood. 2001 May; 84(5): 440-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11316696&dopt=Abstract

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Short-term human growth hormone therapy for HIV-associated wasting. Author(s): Nemechek PM. Source: Aids Patient Care and Stds. 1999 July; 13(7): 391-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10870592&dopt=Abstract

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Short-term recombinant human growth hormone therapy does not modify growth hormone, thyrotropin and prolactin responses to thyrotropin-releasing hormone in adult dialysis patients. Author(s): Iglesias P, Selgas R, Mendez J, Fernandez-Reyes MJ, Bajo MA, Aguilera A, Diez JJ. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 2000 June; 15(6): 85661. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10831641&dopt=Abstract

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Side effects and sociobehavioral factors associated with the discontinuation of hormone therapy in a Massachusetts health maintenance organization. Author(s): Reynolds RF, Obermeyer CM, Walker AM, Guilbert D. Source: Menopause (New York, N.Y.). 2001 May-June; 8(3): 189-99. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11355041&dopt=Abstract

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Specific factors predict the response to pulsatile gonadotropin-releasing hormone therapy in polycystic ovarian syndrome. Author(s): Gill S, Taylor AE, Martin KA, Welt CK, Adams JM, Hall JE. Source: The Journal of Clinical Endocrinology and Metabolism. 2001 June; 86(6): 2428-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11397835&dopt=Abstract

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Successful withdrawal of thyroid hormone therapy in nursing home patients. Author(s): Coll PP, Abourizk NN. Source: The Journal of the American Board of Family Practice / American Board of Family Practice. 2000 November-December; 13(6): 403-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11117336&dopt=Abstract

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Symptomatic versus substitution growth hormone therapy in short children: from auxology towards a comprehensive multidimensional assessment of short stature and related interventions. Author(s): Haverkamp F, Eiholzer U, Ranke MB, Noeker M. Source: J Pediatr Endocrinol Metab. 2000 April; 13(4): 403-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10776994&dopt=Abstract

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The 2nd conference on Asian trends in prostate cancer hormone therapy. Author(s): Akaza H, Chang SJ, Chen KK, Esuvaranathan K, Fujioka T, Hirao Y, Hong SJ, Hinotsu S, Kim WJ, Lau W, Lee SE, Murai M, Naito S, Ogawa O, Rim JS, Soebadi DM, Song JM, Tsukamoto T, Umbas R, Usami M, Yang CR, Yoon JH, Zhou L. Source: Gan to Kagaku Ryoho. 2003 October; 30(10): 1533-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14584292&dopt=Abstract

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The anabolic effects of parathyroid hormone therapy. Author(s): Rubin MR, Bilezikian JP. Source: Clinics in Geriatric Medicine. 2003 May; 19(2): 415-32. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12916294&dopt=Abstract

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The effect of 3 years of recombinant growth hormone therapy on glucose metabolism in short Chinese children with beta-thalassemia major. Author(s): Kwan EY, Tam SC, Cheung PT, Low LC. Source: J Pediatr Endocrinol Metab. 2000 May; 13(5): 545-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10803873&dopt=Abstract

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The effect of growth hormone therapy on mandibular and cranial base development in children treated with total body irradiation. Author(s): Forsberg CM, Krekmanova L, Dahllof G. Source: European Journal of Orthodontics. 2002 June; 24(3): 285-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12143092&dopt=Abstract

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The evolving role of hormone therapy in advanced prostate cancer. Author(s): Dreicer R. Source: Cleve Clin J Med. 2000 October; 67(10): 720-2, 725-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11060958&dopt=Abstract

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The hormone therapy dilemma: women respond. Author(s): Breslau ES, Davis WW, Doner L, Eisner EJ, Goodman NR, Meissner HI, Rimer BK, Rossouw JE. Source: J Am Med Womens Assoc. 2003 Winter; 58(1): 33-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12553641&dopt=Abstract

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The meaning of mammographic breast density in users of postmenopausal hormone therapy. Author(s): Speroff L. Source: Maturitas. 2002 March 25; 41(3): 171-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11886762&dopt=Abstract

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The menopausal hormone therapy elephant: the blind men see. Author(s): Strickler RC. Source: Fertility and Sterility. 2003 September; 80(3): 496. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12969686&dopt=Abstract

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The menopause and HRT. Urogenital effects of hormone therapy. Author(s): Robinson D, Cardozo L. Source: Best Practice & Research. Clinical Endocrinology & Metabolism. 2003 March; 17(1): 91-104. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12763514&dopt=Abstract

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The role of treatment intentions and concerns about side effects in women's decision to discontinue postmenopausal hormone therapy. Author(s): Reynolds RF, Obermeyer CM, Walker AM, Guilbert D. Source: Maturitas. 2002 November 20; 43(3): 183-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12443835&dopt=Abstract

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The somatotrophic system in patients with dilated cardiomyopathy: relation of insulin-like growth factor-1 and its alterations during growth hormone therapy to cardiac function. Author(s): Osterziel KJ, Ranke MB, Strohm O, Dietz R. Source: Clinical Endocrinology. 2000 July; 53(1): 61-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10931081&dopt=Abstract

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The timing of hormone therapy for men with asymptomatic advanced prostate cancer. Author(s): Messing E. Source: Urologic Oncology. 2003 July-August; 21(4): 245-54. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12954493&dopt=Abstract

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Understanding the divergent data on postmenopausal hormone therapy. Author(s): Grodstein F, Clarkson TB, Manson JE. Source: The New England Journal of Medicine. 2003 February 13; 348(7): 645-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12584376&dopt=Abstract

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Urinary tract infections in postmenopausal women: effect of hormone therapy and risk factors. Author(s): Brown JS, Vittinghoff E, Kanaya AM, Agarwal SK, Hulley S, Foxman B; Heart and Estrogen/Progestin Replacement Study Research Group. Source: Obstetrics and Gynecology. 2001 December; 98(6): 1045-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11755552&dopt=Abstract

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Vitamins and hormone therapy for coronary atherosclerosis. Author(s): Hathcock JN. Source: Jama : the Journal of the American Medical Association. 2003 February 26; 289(8): 982; Author Reply 982. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12597741&dopt=Abstract

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What is the role of growth-hormone therapy in short children who were small for gestational age? Author(s): Donaldson M. Source: Lancet. 2001 August 4; 358(9279): 347-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11502309&dopt=Abstract

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Who needs growth hormone therapy? Growth hormone helps some, but its use as an “anti-aging” agent is dubious. Author(s): Frohman LA. Source: Health News. 2002 October; 8(10): 4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12416482&dopt=Abstract

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Why individualizing hormone therapy is crucial: putting the results of the WHI trial into perspective. Author(s): Notelovitz M; Women's Health Initiative. Source: Medscape Women's Health [electronic Resource]. 2002 July-August; 7(4): 9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12466741&dopt=Abstract

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Widespread increases of cortical serotonin type 2A receptor availability after hormone therapy in euthymic postmenopausal women. Author(s): Moses-Kolko EL, Berga SL, Greer PJ, Smith G, Cidis Meltzer C, Drevets WC. Source: Fertility and Sterility. 2003 September; 80(3): 554-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12969697&dopt=Abstract

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Women's knowledge of hormone therapy. Author(s): Coo H, O'Connor KS, Hunter D. Source: Patient Education and Counseling. 2001 December 15; 45(4): 295-301. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11755775&dopt=Abstract

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CHAPTER 2. NUTRITION AND HORMONE THERAPY Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and hormone therapy.

Finding Nutrition Studies on Hormone Therapy 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.4 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 “hormone therapy” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.

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

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

Characteristics of growth hormone therapy for pediatric patients with brain tumors in the National Cooperative Growth Study (NCGS) and from a survey of pediatric endocrinologists. Author(s): Emory University and Children's Healthcare of Atlanta, GA 30033, USA. [email protected] Source: Meacham, L R Sullivan, K J-Pediatr-Endocrinol-Metab. 2002 May; 15 Suppl 2: 689-96

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Expanded spectrum of recombinant human growth hormone therapy. Author(s): Division of Pediatric Endocrinology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104-4318, USA. Source: Henwood, M J Grimberg, A Moshang, T Jr Curr-Opin-Pediatr. 2002 August; 14(4): 437-42 1040-8703

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Growth hormone therapy in Noonan's syndrome: non-cardiomyopathic congenital heart disease does not adversely affect growth improvement. Author(s): Child Life & Health, University of Edinburgh, London, UK. [email protected] Source: Brown, D C Macfarlane, C E McKenna, W J Patton, M A Dunger, D B Savage, M O Kelnar, C J J-Pediatr-Endocrinol-Metab. 2002 June; 15(6): 851-2

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Iatrogenic Creutzfeldt-Jakob disease following human growth hormone therapy: case report. Author(s): Department of Neurology, Medical School, University of Sao Paulo, Sao Paulo, SP, Brazil. Source: Caboclo, L O Huang, N Lepski, G A Livramento, J A Buchpiguel, C A Porto, C S Nitrini, R Arq-Neuropsiquiatr. 2002 June; 60(2-B): 458-61 0004-282X

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Low dose 25 mg oestradiol implants and 1 mg norethisterone as continuous combined hormone therapy: a prospective study. Author(s): Academic Department of Obstetrics and Gynaecology, Chelsea and Westminster Hospital, London, UK. Source: Panay, N Zamblera, D Sands, R Jones, J Alaghband Zadeh, J Studd, J W BJOG. 2002 August; 109(8): 958-60 1470-0328

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Responses of bone turnover markers and bone mineral density to growth hormone therapy in children with isolated growth hormone deficiency and multiple pituitary hormone deficiencies. Author(s): Division of Pediatric Endocrinology, Ihsan Dogramaci Children's Hospital, Hacettepe University, Ankara, Turkey. Source: Kandemir, N Gonc, E N Yordam, N J-Pediatr-Endocrinol-Metab. 2002 June; 15(6): 809-16

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Resumption of growth after methionyl-free human growth hormone therapy in a patient with neutralizing antibodies to methionyl human growth hormone. Author(s): Childrens Hospital Los Angeles, Department of Pediatrics, The Keck School of Medicine of the University of Southern California, USA. [email protected] Source: Pitukcheewanont, P Schwarzbach, L Kaufman, F R J-Pediatr-Endocrinol-Metab. 2002 May; 15(5): 653-7

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The effect of growth hormone therapy on mandibular and cranial base development in children treated with total body irradiation. Author(s): Departments of Orthodontics and Paediatric Dentistry, Karolinska Institutet, Huddinge, Sweden.

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Source: Forsberg, C M Krekmanova, L Dahllof, G Eur-J-Orthod. 2002 June; 24(3): 285-92 0141-5387 •

Who needs growth hormone therapy? Growth hormone helps some, but its use as an “anti-aging” agent is dubious. Author(s): University of Illinois at Chicago, USA. Source: Frohman, L A Health-News. 2002 October; 8(10): 4 1081-5880

Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: •

healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0

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

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

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

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The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/

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

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

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Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/

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

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

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

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

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

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

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

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

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

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CHAPTER 3. ALTERNATIVE MEDICINE AND HORMONE THERAPY Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to hormone therapy. 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 hormone therapy 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 “hormone therapy” (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 hormone therapy: •

“Bust enhancing” herbal products. Author(s): Fugh-Berman A. Source: Obstetrics and Gynecology. 2003 June; 101(6): 1345-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12798545&dopt=Abstract

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“Governare il diabete” (“to steer diabetes”): a new proposal for diabetic camps. Author(s): Salvatoni A, Pompili V, Biasoli R, Cardani R, Arioli G, Nespoli L. Source: Acta Biomed Ateneo Parmense. 2003; 74 Suppl 1: 29-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12817799&dopt=Abstract

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Counseling patients who elect to discontinue hormone therapy. Author(s): Simon JA, Mack CJ.

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Source: Int J Fertil Womens Med. 2003 May-June; 48(3): 111-6; Discussion 137-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12839141&dopt=Abstract •

Is bio-identical hormone therapy fact or fairy tale? Author(s): Francisco L. Source: The Nurse Practitioner. 2003 July; 28(7 Pt 1): 39-44, Table of Contents. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12861094&dopt=Abstract

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Vitamins and hormone therapy for coronary atherosclerosis. Author(s): Hathcock JN. Source: Jama : the Journal of the American Medical Association. 2003 February 26; 289(8): 982; Author Reply 982. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12597741&dopt=Abstract

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Widespread increases of cortical serotonin type 2A receptor availability after hormone therapy in euthymic postmenopausal women. Author(s): Moses-Kolko EL, Berga SL, Greer PJ, Smith G, Cidis Meltzer C, Drevets WC. Source: Fertility and Sterility. 2003 September; 80(3): 554-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12969697&dopt=Abstract

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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The following is a specific Web list relating to hormone therapy; 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 Amenorrhea Source: Integrative Medicine Communications; www.drkoop.com Endometriosis Source: Healthnotes, Inc.; www.healthnotes.com Female Infertility Source: Healthnotes, Inc.; www.healthnotes.com Female Infertility Source: Prima Communications, Inc.www.personalhealthzone.com Menopause Source: Integrative Medicine Communications; www.drkoop.com Prostate Cancer Source: Healthnotes, Inc.; www.healthnotes.com

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Herbs and Supplements Red Clover Source: Integrative Medicine Communications; www.drkoop.com Vitex Alternative names: Vitex agnus-castus Source: Healthnotes, Inc.; www.healthnotes.com

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

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

Dissertations on Hormone Therapy 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 hormone therapy. 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: •

Antibodies to Pituitary Hormones Induced by Polypeptide Hormone Therapy by Murthy, Gollapudi G; ADVDEG from McGill University (Canada), 1971 http://wwwlib.umi.com/dissertations/fullcit/NK09789

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Mediating Medicine: Controversy, Credibility, and the Use of Alternatives to Conventional Hormone Therapy by Carter, Marilyn Jo; PhD from University of Oregon, 2000, 172 pages http://wwwlib.umi.com/dissertations/fullcit/9978250

Keeping Current Ask the medical librarian at your library if it has full and unlimited access to the ProQuest Digital Dissertations database. From the library, you should be able to do more complete searches via http://wwwlib.umi.com/dissertations.

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CHAPTER 5. CLINICAL TRIALS AND HORMONE THERAPY Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning hormone therapy.

Recent Trials on Hormone Therapy The following is a list of recent trials dedicated to hormone therapy.5 Further information on a trial is available at the Web site indicated. •

Arsenic Trioxide in Treating Patients With Stage IV Prostate Cancer That Has Not Responded to Previous Hormone Therapy Condition(s): stage IV prostate cancer; recurrent prostate cancer Study Status: This study is currently recruiting patients. Sponsor(s): Albert Einstein Cancer Research Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. PURPOSE: Phase II trial to study the effectiveness of arsenic trioxide in treating patients who have stage IV prostate cancer that has not responded to hormone therapy. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004149

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BMS-247550 in Treating Patients With Prostate Cancer That Has Not Responded to Hormone Therapy Condition(s): adenocarcinoma of the prostate; stage IV prostate cancer; recurrent prostate cancer Study Status: This study is currently recruiting patients.

5

These are listed at www.ClinicalTrials.gov.

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Sponsor(s): Southwest Oncology Group; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. PURPOSE: Phase II trial to study the effectiveness of BMS-247550 in treating patients who have prostate cancer that has not responded to hormone therapy. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00016393 •

Chemotherapy Plus Hormone Therapy Versus Androgen Suppression in Treating Patients With Metastatic or Unresectable Prostate Cancer Condition(s): adenocarcinoma of the prostate; stage III prostate cancer; stage IV prostate cancer; recurrent prostate cancer Study Status: This study is currently recruiting patients. Sponsor(s): M.D. Anderson Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining hormone therapy with chemotherapy and androgen suppression may kill more tumor cells. It is not yet known which treatment regimen is more effective for prostate cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of chemotherapy plus hormone therapy versus androgen suppression alone as initial therapy in patients with prostate cancer that is metastatic or that cannot be removed surgically. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00002855

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Chemotherapy With or Without Biological Therapy in Treating Patients With Metastatic Prostate Cancer That Has Not Responded to Hormone Therapy Condition(s): adenocarcinoma of the prostate; stage IV prostate cancer; recurrent prostate cancer Study Status: This study is currently recruiting patients. Sponsor(s): Eastern Cooperative Oncology Group; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. Biological therapies use different ways to stimulate the immune system and stop cancer cells from growing. It is not yet known which treatment regimen is more effective in treating metastatic prostate cancer. PURPOSE: Randomized phase II trial to compare the effectiveness of combination chemotherapy with that of chemotherapy plus biological therapy in treating patients who have progressive or metastatic prostate cancer that has not responded to hormone therapy. Phase(s): Phase II Study Type: Interventional

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Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005847 •

Chemotherapy, Hormone Therapy, and Radiation Therapy in Treating Patients with Locally Advanced Prostate Cancer Condition(s): adenocarcinoma of the prostate; stage III prostate cancer; stage IV prostate cancer Study Status: This study is currently recruiting patients. Sponsor(s): Cancer and Leukemia Group B; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Androgens can stimulate the growth of prostate cancer cells. Drugs such as goserelin or leuprolide may stop the adrenal glands from producing androgens. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining chemotherapy, hormone therapy, and radiation therapy may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of combining chemotherapy, hormone therapy, and radiation therapy in treating patients who have locally advanced prostate cancer. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00016913

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Combination Chemotherapy Plus Hormone Therapy in Treating Patients With Metastatic Prostate Cancer Condition(s): adenocarcinoma of the prostate; stage IV prostate cancer; recurrent prostate cancer Study Status: This study is currently recruiting patients. Sponsor(s): Southwest Oncology Group; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Androgens can stimulate the growth of prostate cancer cells. Drugs such as goserelin, leuprolide, flutamide, or bicalutamide may stop the adrenal glands from producing androgens. Combining chemotherapy with hormone therapy may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy plus hormone therapy in treating patients who have metastatic prostate cancer. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00028769

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Docetaxel, Estramustine, and Exisulind in Treating Patients With Metastatic Prostate Cancer That Has Not Responded to Hormone Therapy Condition(s): adenocarcinoma of the prostate; recurrent prostate cancer; stage IV prostate cancer

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Study Status: This study is currently recruiting patients. Sponsor(s): Cancer and Leukemia Group B; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Androgens can stimulate the growth of prostate cancer cells. Estramustine may fight prostate cancer by reducing the production of androgens. Exisulind may stop the growth of prostate cancer by stopping blood flow to the tumor. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining these therapies may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of combining estramustine with exisulind and docetaxel in treating patients who have metastatic prostate cancer that has not responded to hormone therapy. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00052845 •

Docetaxel, Estramustine, and Thalidomide in Treating Patients With Prostate Cancer Previously Treated With Hormone Therapy Condition(s): adenocarcinoma of the prostate; stage IV prostate cancer; recurrent prostate cancer Study Status: This study is currently recruiting patients. Sponsor(s): Whittingham Cancer Center Purpose - Excerpt: RATIONALE: Thalidomide may stop the growth of prostate cancer by stopping blood flow to the tumor. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with thalidomide may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of combining docetaxel and estramustine with thalidomide in treating patients who have prostate cancer previously treated with hormone therapy. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00046826

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Hormone Therapy and OGX-011 Before Radical Prostatectomy in Treating Patients With Prostate Cancer Condition(s): adenocarcinoma of the prostate; stage III prostate cancer; stage II prostate cancer Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute of Canada Purpose - Excerpt: RATIONALE: Androgens can stimulate the growth of prostate cancer cells. Drugs such as flutamide and buserelin may stop the adrenal glands from producing androgens. OGX-011 may help flutamide and buserelin kill more tumor cells by making tumor cells more sensitive to the drugs. Giving flutamide and buserelin with OGX-011 before surgery may shrink the tumor so it can be removed during surgery. PURPOSE: Phase I trial to study the effectiveness of combining hormone therapy with OGX-011 before radical prostatectomy in treating patients who have prostate cancer.

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Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00054106 •

Hormone Therapy and Radiation Therapy in Treating Patients With Prostate Cancer Condition(s): adenocarcinoma of the prostate; stage II prostate cancer; stage III prostate cancer Study Status: This study is currently recruiting patients. Sponsor(s): Radiation Therapy Oncology Group; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Hormones can stimulate the growth of prostate cancer cells. Hormone therapy may fight prostate cancer by reducing the production of androgens. Radiation therapy uses high-energy x-rays to damage tumor cells. It is not yet known which regimen of hormone therapy and radiation therapy is more effective for prostate cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of two different regimens of hormone therapy and radiation therapy in treating patients who have prostate cancer. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005044

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Hormone Therapy Compared With Combination Chemotherapy in Treating Patients With Prostate Cancer Condition(s): adenocarcinoma of the prostate; stage III prostate cancer Study Status: This study is currently recruiting patients. Sponsor(s): Eastern Cooperative Oncology Group; National Cancer Institute (NCI); Southwest Oncology Group; Cancer and Leukemia Group B Purpose - Excerpt: RATIONALE: Androgens can stimulate the growth of prostate cancer cells. Drugs such as ketoconazole may stop the production of androgens. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known whether hormone therapy is more effective than combination chemotherapy in treating prostate cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of hormone therapy with that of combination chemotherapy in treating patients who have prostate cancer that has been previously treated with androgen suppression. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00027859

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Hormone Therapy Followed By Internal Radiation Therapy in Treating Patients With Locally Recurrent Prostate Cancer Condition(s): adenocarcinoma of the prostate; stage I prostate cancer; stage II prostate cancer; recurrent prostate cancer Study Status: This study is currently recruiting patients. Sponsor(s): North Central Cancer Treatment Group; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Androgens can stimulate the growth of prostate cancer cells. Drugs such as goserelin, leuprolide, flutamide, or bicalutamide may stop the adrenal glands from producing androgens. Internal radiation uses radioactive material placed directly into or near a tumor to kill tumor cells. Combining hormone therapy with internal radiation may be effective in treating locally recurrent prostate cancer. PURPOSE: Phase II trial to study the effectiveness of hormone therapy followed by internal radiation in treating patients who have locally recurrent prostate cancer following external-beam radiation therapy. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00032006

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Hormone Therapy in Preventing Cancer in Women With a Genetic Risk For Endometrial Cancer Condition(s): Endometrial Cancer Study Status: This study is currently recruiting patients. Sponsor(s): M.D. Anderson Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Hormone therapy may prevent the development of endometrial cancer. It is not yet known which hormone therapy regimen is more effective in preventing endometrial cancer. PURPOSE: Randomized phase II trial to compare different hormone therapy regimens in preventing endometrial cancer in women who have a genetic risk for endometrial cancer. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00033358

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Hormone Therapy in Treating Men With Stage IV Prostate Cancer Condition(s): adenocarcinoma of the prostate; stage IV prostate cancer; recurrent prostate cancer Study Status: This study is currently recruiting patients. Sponsor(s): Southwest Oncology Group; National Cancer Institute (NCI); National Cancer Institute of Canada; Cancer and Leukemia Group B; Eastern Cooperative Oncology Group; EORTC Genito-Urinary Tract Cancer Cooperative Group Purpose - Excerpt: RATIONALE: Testosterone can stimulate the growth of prostate cancer cells. Hormone therapy may be effective treatment for prostate cancer. It is not yet known which regimen of hormone therapy is most effective for stage IV prostate

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cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of two hormone therapy regimens in treating men who have stage IV prostate cancer. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00002651 •

Hormone Therapy in Treating Patients With Rising PSA Levels Following Radiation Therapy for Prostate Cancer Condition(s): adenocarcinoma of the prostate; recurrent prostate cancer Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute of Canada; National Cancer Institute (NCI); Southwest Oncology Group Purpose - Excerpt: RATIONALE: Androgens can stimulate the growth of prostate cancer cells. Hormone therapy may fight prostate cancer by reducing the production of androgens. It is not yet known which androgen suppression regimen is more effective for prostate cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of two hormone therapy regimens in treating patients with rising PSA levels following radiation therapy for prostate cancer. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003653

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Hormone Therapy Plus Chemotherapy in Treating Patients With Prostate Cancer Condition(s): adenocarcinoma of the prostate; stage II prostate cancer; stage III prostate cancer; stage IV prostate cancer; recurrent prostate cancer Study Status: This study is currently recruiting patients. Sponsor(s): Radiation Therapy Oncology Group; National Cancer Institute (NCI); Eastern Cooperative Oncology Group Purpose - Excerpt: RATIONALE: Androgens can stimulate the growth of prostate cancer cells. Drugs such as goserelin, leuprolide, flutamide, or bicalutamide may stop the adrenal glands from producing androgens. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining hormone therapy with chemotherapy may kill more tumor cells. It is not yet known if chemotherapy given at the same time as hormone therapy is more effective than chemotherapy given after hormone therapy in treating prostate cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of chemotherapy given at the same time as hormone therapy with that of chemotherapy given after hormone therapy in treating patients who have prostate cancer. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00030654

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Hormone Therapy Plus Radiation Therapy With or Without Combination Chemotherapy in Treating Patients With Prostate Cancer Condition(s): stage II prostate cancer; stage III prostate cancer; stage IV prostate cancer Study Status: This study is currently recruiting patients. Sponsor(s): Radiation Therapy Oncology Group; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Hormones can stimulate the production of prostate cancer cells. Hormone therapy may fight prostate cancer by reducing the production of androgens. Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known whether hormone therapy plus radiation therapy is more effective with or without combination chemotherapy for prostate cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of hormone therapy plus radiation therapy with or without combination chemotherapy in treating patients who have prostate cancer. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004054

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Hormone Therapy With or Without Docetaxel And Estramustine in Treating Patients With Prostate Cancer That is Locally Advanced or At High Risk of Relapse Condition(s): stage III prostate cancer; stage II prostate cancer Study Status: This study is currently recruiting patients. Sponsor(s): Federation Nationale des Centres de Lutte Contre le Cancer Purpose - Excerpt: RATIONALE: Androgens can stimulate the growth of prostate cancer cells. Drugs such as nilutamide, bicalutamide, flutamide, or cyproterone may stop the adrenal glands from producing androgens. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known whether hormone therapy is more effective with or without chemotherapy in treating prostate cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of hormone therapy with or without docetaxel and estramustine in treating patients who have prostate cancer that is locally advanced or at high risk of relapse. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00055731

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Hormone Therapy With or Without Mitoxantrone and Prednisone in Treating Patients Who Have Undergone Radical Prostatectomy for Prostate Cancer Condition(s): adenocarcinoma of the prostate; stage I prostate cancer; stage II prostate cancer; stage III prostate cancer; stage IV prostate cancer; recurrent prostate cancer Study Status: This study is currently recruiting patients. Sponsor(s): Southwest Oncology Group; National Cancer Institute (NCI); Cancer and Leukemia Group B

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Purpose - Excerpt: RATIONALE: Hormones can stimulate the production of prostate cancer cells. Hormone therapy may fight prostate cancer by reducing the production of androgens. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known whether hormone therapy plus mitoxantrone and prednisone is more effective than hormone therapy alone for prostate cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of hormone therapy with or without mitoxantrone and prednisone in treating patients who have undergone radical prostatectomy for prostate cancer. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004124 •

Hormone Therapy With or Without Surgery or Radiation Therapy in Treating Patients With Prostate Cancer Condition(s): adenocarcinoma of the prostate; stage II prostate cancer; stage III prostate cancer; stage IV prostate cancer Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute of Canada; National Cancer Institute (NCI); Eastern Cooperative Oncology Group; Cancer and Leukemia Group B; Southwest Oncology Group; Medical Research Council Purpose - Excerpt: RATIONALE: Hormones can stimulate the growth of prostate cancer cells. Hormone therapy may fight prostate cancer by reducing the production of androgens. Radiation therapy uses high-energy x-rays to damage tumor cells. It is not yet known whether hormone therapy plus surgery is more effective than hormone therapy plus radiation therapy for prostate cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of hormone therapy alone, hormone therapy plus bilateral orchiectomy, or hormone therapy plus radiation therapy in treating patients who have stage III or stage IV prostate cancer. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00002633

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Monoclonal Antibody Therapy Plus Chemotherapy Followed by Peripheral Stem Cell Transplantation in Treating Patients With Metastatic Prostate Cancer That Has Not Responded to Hormone Therapy Condition(s): stage IV prostate cancer; recurrent prostate cancer Study Status: This study is currently recruiting patients. Sponsor(s): University of California Davis Cancer Center Purpose - Excerpt: RATIONALE: Radiolabeled monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining monoclonal antibody therapy and chemotherapy with peripheral stem cell transplantation may be an effective treatment

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for metastatic prostate cancer. PURPOSE: Phase I trial to study the effectiveness of monoclonal antibody therapy plus chemotherapy followed by peripheral stem cell transplantation in treating patients who have metastatic prostate cancer that has not responded to hormone therapy. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00009750 •

Paclitaxel and Carboplatin in Treating Patients With Metastatic Prostate Cancer That Has Not Responded to Hormone Therapy Condition(s): adenocarcinoma of the prostate; recurrent prostate cancer; stage IV prostate cancer Study Status: This study is currently recruiting patients. Sponsor(s): Jonsson Comprehensive Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of combining paclitaxel with carboplatin in treating patients who have metastatic prostate cancer that has not responded to hormone therapy. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00049257

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Radiation Therapy Plus Hormone Therapy Compared With Radiation Therapy Alone in Treating Patients With Stage II or Stage III Prostate Cancer Condition(s): stage III prostate cancer; stage II prostate cancer Study Status: This study is currently recruiting patients. Sponsor(s): Radiation Therapy Oncology Group; National Cancer Institute (NCI); National Cancer Institute of Canada Purpose - Excerpt: RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Androgens can stimulate the growth of prostate cancer cells. Drugs such as goserelin, leuprolide, flutamide, or bicalutamide may stop the adrenal glands from producing androgens. Combining radiation therapy with hormone therapy may be an effective treatment for stage II or stage III prostate cancer. It is not yet known if radiation therapy combined with hormone therapy is more effective than either radiation therapy alone or hormone therapy alone in treating stage II or stage III prostate cancer. (Hormone therapy alone group closed as of 12/9/2002.) PURPOSE: Randomized phase III trial to compare the effectiveness of radiation therapy plus hormone therapy to that of radiation therapy alone or hormone therapy alone in treating patients who have stage II or stage III prostate cancer. Phase(s): Phase III Study Type: Interventional

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Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00023829 •

Testosterone in Treating Patients With Progressive Prostate Cancer That No Longer Responds to Hormone Therapy Condition(s): stage IV prostate cancer; recurrent prostate cancer Study Status: This study is currently recruiting patients. Sponsor(s): Memorial Sloan-Kettering Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: High doses of testosterone may be effective in killing prostate cancer cells that no longer respond to hormone therapy. PURPOSE: Phase I trial to study the effectiveness of testosterone in treating patients who have progressive prostate cancer that no longer responds to hormone therapy. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006044

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BMS-275291 in Treating Patients With Prostate Cancer That Has Not Responded to Hormone Therapy Condition(s): adenocarcinoma of the prostate; stage IV prostate cancer; recurrent prostate cancer Study Status: This study is no longer recruiting patients. Sponsor(s): University of California Davis Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: BMS-275291 may stop the growth of prostate cancer by stopping blood flow to the tumor and by blocking the enzymes necessary for tumor cell growth. PURPOSE: Randomized phase II trial to study the effectiveness of BMS-275291 in treating patients who have prostate cancer that has not responded to hormone therapy. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00040755

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Calcitriol Plus Dexamethasone in Treating Patients With Prostate Cancer That Has Not Responded to Hormone Therapy Condition(s): stage III prostate cancer; stage IV prostate cancer; adenocarcinoma of the prostate; recurrent prostate cancer Study Status: This study is no longer recruiting patients. Sponsor(s): National Cancer Institute (NCI); University of Pittsburgh Cancer Institute Purpose - Excerpt: RATIONALE: Combining calcitriol with dexamethasone may increase the effectiveness of therapy by making cancer cells more sensitive to dexamethasone. PURPOSE: Phase I trial to study the effectiveness of calcitriol combined

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with dexamethasone in treating patients who have prostate cancer that has not responded to previous hormone therapy. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00010231 •

Chemotherapy and Hormone Therapy in Treating Patients With Prostate Cancer Condition(s): adenocarcinoma of the prostate; stage I prostate cancer Study Status: This study is no longer recruiting patients. Sponsor(s): University of Massachusetts Medical Center Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Androgens can stimulate the growth of prostate cancer cells. Hormone therapy using bicalutamide and leuprolide may fight prostate cancer by reducing the production of androgens. PURPOSE: Phase II trial to study the effectiveness of chemotherapy consisting of docetaxel and estramustine plus hormone therapy in treating patients who have previously undergone radiation therapy or surgical removal of the prostate for stage I prostate cancer. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003915

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Combination Chemotherapy Compared With Hormone Therapy in Treating Patients With Recurrent, Stage III, or Stage IV Endometrial Cancer Condition(s): stage III endometrial cancer; stage IV endometrial cancer; recurrent endometrial cancer Study Status: This study is no longer recruiting patients. Sponsor(s): National Cancer Institute (NCI); Gynecologic Oncology Group Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Estrogen can stimulate the growth of tumor cells. Hormone therapy using tamoxifen and megestrol may fight endometrial cancer by blocking the absorption of estrogen. It is not yet known whether chemotherapy is more effective than hormone therapy in treating endometrial cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of combination chemotherapy with that of hormone therapy in treating patients who have recurrent, stage III, or stage IV endometrial cancer. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00016341

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Combination Chemotherapy in Treating Patients With Metastatic Prostate Cancer That Has Not Responded to Hormone Therapy Condition(s): adenocarcinoma of the prostate; stage IV prostate cancer; recurrent prostate cancer Study Status: This study is no longer recruiting patients. Sponsor(s): GERCOR Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy in treating patients who have metastatic prostate cancer that has not responded to hormone therapy. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006114

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Combination Therapy in Treating Patients With Advanced Prostate Cancer That Has Not Responded to Hormone Therapy Condition(s): adenocarcinoma of the prostate; stage IV prostate cancer; recurrent prostate cancer Study Status: This study is no longer recruiting patients. Sponsor(s): Southwest Oncology Group; National Cancer Institute (NCI); Cancer and Leukemia Group B; North Central Cancer Treatment Group Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy and hormone therapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug and giving drugs in different ways may kill more tumor cells. It is not yet known whether estramustine plus docetaxel is more effective than mitoxantrone plus prednisone for prostate cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of estramustine plus docetaxel with that of mitoxantrone plus prednisone in treating patients who have stage IV prostate cancer that has not responded to hormone therapy. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004001

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Hormone Therapy in Treating Patients Who Have Stage I or Stage II Prostate Cancer Condition(s): stage II prostate cancer; stage I prostate cancer Study Status: This study is no longer recruiting patients. Sponsor(s): National Cancer Institute (NCI); Eastern Cooperative Oncology Group; M.D. Anderson Cancer Center Purpose - Excerpt: RATIONALE: Testosterone can stimulate the growth of prostate cancer cells. Hormone therapy using leuprolide and flutamide may fight prostate cancer by reducing the production of testosterone. It is not yet known whether receiving

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leuprolide and flutamide is more effective than receiving no further therapy. PURPOSE: Randomized phase III trial to determine the effectiveness of hormone therapy in treating patients who have stage I or stage II prostate cancer that is at high risk of recurrence and who have already undergone surgery. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003645 •

Hormone Therapy in Treating Patients With Advanced Prostate Cancer Condition(s): adenocarcinoma of the prostate Study Status: This study is no longer recruiting patients. Sponsor(s): EORTC Radiotherapy Cooperative Group; EORTC Genito-Urinary Tract Cancer Cooperative Group Purpose - Excerpt: RATIONALE: Androgens can stimulate the growth of prostate cancer cells. Hormone therapy using triptorelin may fight prostate cancer by reducing the production of androgens. PURPOSE: Randomized phase III trial to compare the effectiveness of long-term hormone therapy and triptorelin with no further treatment in treating patients who have advanced prostate cancer previously treated with radiation therapy and 6 months of androgen suppression. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003026

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Hormone Therapy in Treating Patients With Prostate Cancer Condition(s): adenocarcinoma of the prostate; recurrent prostate cancer; Quality of Life; sexual dysfunction and infertility Study Status: This study is no longer recruiting patients. Sponsor(s): National Cancer Institute (NCI); Cancer and Leukemia Group B Purpose - Excerpt: RATIONALE: Male hormones can stimulate the growth of prostate cancer cells. Hormone therapy using flutamide and finasteride may fight prostate cancer by reducing the production of male hormones. PURPOSE: Phase II trial to study the effectiveness of flutamide and finasteride in treating prostate cancer patients with high PSA levels who were previously treated with radiation therapy or radical prostatectomy. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003323

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Hormone Therapy Plus Chemotherapy in Treating Children With Acute Lymphocytic Leukemia Condition(s): recurrent childhood acute lymphoblastic leukemia; untreated childhood acute lymphoblastic leukemia Study Status: This study is no longer recruiting patients. Sponsor(s): Medical Research Council Purpose - Excerpt: RATIONALE: Hormone therapy may stop the growth of cancer cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining hormone therapy with chemotherapy may kill more tumor cells. It is not yet known which hormone therapy and chemotherapy regimen is most effective for acute lymphocytic leukemia. PURPOSE: Randomized phase III trial to compare the effectiveness of different steroids and chemotherapy drugs in treating children who have acute lymphocytic leukemia. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003437

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Hormone Therapy Plus Radiation Therapy in Treating Patients With Prostate Cancer Condition(s): stage II prostate cancer; stage III prostate cancer; stage I prostate cancer; adenocarcinoma of the prostate Study Status: This study is no longer recruiting patients. Sponsor(s): National Cancer Institute (NCI); Herbert Irving Comprehensive Cancer Center Purpose - Excerpt: RATIONALE: Androgens can stimulate the growth of prostate cancer cells. Hormone therapy using leuprolide and flutamide may fight prostate cancer by reducing the production of androgens. Combining radiation therapy with hormone therapy may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of hormone therapy plus radiation therapy in treating patients with prostate cancer. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003124

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MEN-10755 in Treating Patients With Progressive Prostate Cancer That Has Not Responded to Hormone Therapy Condition(s): adenocarcinoma of the prostate; recurrent prostate cancer Study Status: This study is no longer recruiting patients. Sponsor(s): EORTC New Drug Development Group Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. PURPOSE: Phase II trial to study the effectiveness of MEN-10755 in treating patients who have progressive prostate cancer that has not responded to hormone therapy. Phase(s): Phase II

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Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00027781 •

Radiation Therapy After Surgery, Chemotherapy, and/or Hormone Therapy in Treating Women With Stage II Breast Cancer Condition(s): stage II breast cancer Study Status: This study is no longer recruiting patients. Sponsor(s): Southwest Oncology Group; National Cancer Institute (NCI); North Central Cancer Treatment Group; American College of Surgeons; Eastern Cooperative Oncology Group; Radiation Therapy Oncology Group; Cancer and Leukemia Group B; National Cancer Institute of Canada; National Surgical Adjuvant Breast and Bowel Project (NSABP) Purpose - Excerpt: RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. It is not yet known whether mastectomy, chemotherapy, and/or hormone therapy are more effective with or without radiation therapy in treating breast cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of mastectomy, chemotherapy, and/or hormone therapy with or without radiation therapy in treating women who have stage II breast cancer. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005983

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SU5416 Compared to Dexamethasone in Treating Patients With Progressive Prostate Cancer That Has Not Responded to Hormone Therapy Condition(s): stage IV prostate cancer; recurrent prostate cancer Study Status: This study is no longer recruiting patients. Sponsor(s): National Cancer Institute (NCI); University of Chicago Cancer Research Center Purpose - Excerpt: RATIONALE: SU5416 may stop the growth of prostate cancer by stopping blood flow to the tumor. Dexamethasone may be effective in slowing the growth of prostate cancer cells. It is not yet known whether SU5416 or dexamethasone is more effective in treating progressive prostate cancer. PURPOSE: Randomized phase II trial to compare the effectiveness of SU5416 with that of dexamethasone in treating patients who have progressive prostate cancer that has not responded to hormone therapy. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006002

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Trastuzumab and Docetaxel in Treating Patients Who Have Metastatic Prostate Cancer That Is Refractory to Hormone Therapy Condition(s): stage IV prostate cancer; recurrent prostate cancer Study Status: This study is no longer recruiting patients. Sponsor(s): National Cancer Institute (NCI); Beckman Research Institute Purpose - Excerpt: RATIONALE: Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining monoclonal antibody therapy with chemotherapy may kill more tumor cells. PURPOSE: Phase II trial to compare the effectiveness of trastuzumab alone and in combination with docetaxel in treating patients who have metastatic prostate cancer that is refractory to hormone therapy. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005857

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Vaccine Therapy Plus Interleukin-12 in Treating Patients With Metastatic Prostate Cancer That Has Not Responded to Hormone Therapy Condition(s): adenocarcinoma of the prostate; stage IV prostate cancer; recurrent prostate cancer Study Status: This study is no longer recruiting patients. Sponsor(s): University of Chicago Cancer Research Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Vaccines made from a patient's white blood cells may make the body build an immune response to kill cancer cells. Interleukin-12 may kill cancer cells by stopping blood flow to the tumor and by stimulating a person's white blood cells to kill cancer cells. Combining vaccine therapy with interleukin-12 may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of vaccine therapy combined with interleukin-12 in treating patients who have metastatic prostate cancer that has not responded to hormone therapy. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00015977

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ZD 1839 in Treating Patients With Prostate Cancer That Has Not Responded to Hormone Therapy Condition(s): adenocarcinoma of the prostate; recurrent prostate cancer Study Status: This study is no longer recruiting patients. Sponsor(s): National Cancer Institute of Canada Purpose - Excerpt: RATIONALE: Biological therapies such as ZD 1839 may interfere with the growth of tumor cells and slow the growth of prostate cancer. It is not yet

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known which dose of ZD 1839 is more effective in treating prostate cancer that has not responded to hormone therapy. PURPOSE: Randomized phase II trial to compare different doses of ZD 1839 in treating patients who have prostate cancer that has not responded to hormone therapy. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00025116 •

Effects of Hormone Therapy on the Immune Systems of Postmenopausal Women with Chronic Infections Condition(s): Atherosclerosis; Chlamydia Infections; Cytomegalovirus Infections; Pneumonia, Bacterial; Postmenopause Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: Hardening of the arteries (atherosclerosis) and heart disease are much more common in men than in women. However, as women grow older, especially after menopause the incidence of atherosclerosis and heart disease increases. These findings suggest that estrogen may be protective and help in preventing heart disease. Studies of large groups of post-menopausal women suggest that hormone replacement therapy (therapy that includes estrogen) reduces the risk of heart disease. Estrogen causes favorable changes in particles that carry cholesterol in the blood stream and improves function of blood vessels. Estrogen may also stimulate the immune system's ability to fight off infections that may lead to or contribute to atherosclerosis. Researchers believe two specific infectious agents (Chlamydia pneumoniae and human cytomegalovirus) may cause damage to the lining of blood vessels resulting in inflammation and the development of atherosclerosis. The purpose of this study is to determine if estrogen treatment can change how the immune system responds to chronic infections, by Chlamydia pneumoniae and human cytomegalovirus, in postmenopausal women. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001890

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Endometriosis : Traditional Medicine vs Hormone Therapy Condition(s): Endometriosis; Pelvic Pain Study Status: This study is not yet open for patient recruitment. Sponsor(s): National Center for Complementary and Alternative Medicine (NCCAM) Purpose - Excerpt: This 12-week study will determine whether traditional Chinese medicine (acupuncture and Chinese herbs) is as effective as hormone therapy for alleviating endometriosis-related pelvic pain. Phase(s): Phase I; Phase II Study Type: Interventional

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Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00034047 •

Epothilone B in Treating Patients With Prostate Cancer That Has Not Responded to Hormone Therapy and Chemotherapy Condition(s): adenocarcinoma of the prostate; recurrent prostate cancer; stage IV prostate cancer Study Status: This study is not yet open for patient recruitment. Sponsor(s): Eastern Cooperative Oncology Group; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. PURPOSE: Phase II trial to study the effectiveness of epothilone B in treating patients with prostate cancer that has not responded to hormone therapy and chemotherapy. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00052858

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Estramustine, Docetaxel, and Carboplatin in Treating Patients With Prostate Cancer That Has Not Responded to Hormone Therapy Condition(s): adenocarcinoma of the prostate; recurrent prostate cancer Study Status: This study is completed. Sponsor(s): Dana-Farber/Harvard Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. PURPOSE: Phase I trial to study the effectiveness of estramustine, docetaxel, and carboplatin in treating patients who have prostate cancer that has not responded to hormonal therapy. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005627

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Vascular and Metabolic Effects of Hormone Therapy Combined with L-Arginine in Postmenopausal Women Condition(s): Hypercholesterolemia; Postmenopause Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: Estrogen therapy has been associated with reduced risk of coronary heart disease events in observational studies of postmenopausal women. Although favorable effects of estrogen on lipoprotein cholesterol levels probably account for much of this benefit, direct vascular effects (vasomotor, hemostatic, anti-inflammatory) regulated by nitric oxide (NO) may also be of importance. We have recently shown that

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vasodilator effects of estrogen in the coronary circulation are due to enhanced bioactivity of NO released from the endothelium. Estrogen has been shown to stimulate synthesis and activity of the enzyme NO synthase with enhanced NO synthesis in endothelial cells in culture. Because L-arginine is the natural substrate for the enzyme NO synthase, we propose that the combination of L-arginine and estrogen might have additive vasomotor, hemostatic and anti-inflammatory effects in hypercholesterolemic postmenopausal women. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001752

Keeping Current on Clinical Trials The U.S. National Institutes of Health, through the National Library of Medicine, has developed ClinicalTrials.gov to provide current information about clinical research across the broadest number of diseases and conditions. The site was launched in February 2000 and currently contains approximately 5,700 clinical studies in over 59,000 locations worldwide, with most studies being conducted in the United States. ClinicalTrials.gov receives about 2 million hits per month and hosts approximately 5,400 visitors daily. To access this database, simply go to the Web site at http://www.clinicaltrials.gov/ and search by “hormone therapy” (or synonyms). While ClinicalTrials.gov is the most comprehensive listing of NIH-supported clinical trials available, not all trials are in the database. The database is updated regularly, so clinical trials are continually being added. The following is a list of specialty databases affiliated with the National Institutes of Health that offer additional information on trials: •

For clinical studies at the Warren Grant Magnuson Clinical Center located in Bethesda, Maryland, visit their Web site: http://clinicalstudies.info.nih.gov/

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For clinical studies conducted at the Bayview Campus in Baltimore, Maryland, visit their Web site: http://www.jhbmc.jhu.edu/studies/index.html

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For cancer trials, visit the National Cancer Institute: http://cancertrials.nci.nih.gov/

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For eye-related trials, visit and search the Web page of the National Eye Institute: http://www.nei.nih.gov/neitrials/index.htm

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For heart, lung and blood trials, visit the Web page of the National Heart, Lung and Blood Institute: http://www.nhlbi.nih.gov/studies/index.htm

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For trials on aging, visit and search the Web site of the National Institute on Aging: http://www.grc.nia.nih.gov/studies/index.htm

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For rare diseases, visit and search the Web site sponsored by the Office of Rare Diseases: http://ord.aspensys.com/asp/resources/rsch_trials.asp

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For alcoholism, visit the National Institute on Alcohol Abuse and Alcoholism: http://www.niaaa.nih.gov/intramural/Web_dicbr_hp/particip.htm

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For trials on infectious, immune, and allergic diseases, visit the site of the National Institute of Allergy and Infectious Diseases: http://www.niaid.nih.gov/clintrials/

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For trials on arthritis, musculoskeletal and skin diseases, visit newly revised site of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health: http://www.niams.nih.gov/hi/studies/index.htm

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For hearing-related trials, visit the National Institute on Deafness and Other Communication Disorders: http://www.nidcd.nih.gov/health/clinical/index.htm

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For trials on diseases of the digestive system and kidneys, and diabetes, visit the National Institute of Diabetes and Digestive and Kidney Diseases: http://www.niddk.nih.gov/patient/patient.htm

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For drug abuse trials, visit and search the Web site sponsored by the National Institute on Drug Abuse: http://www.nida.nih.gov/CTN/Index.htm

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For trials on mental disorders, visit and search the Web site of the National Institute of Mental Health: http://www.nimh.nih.gov/studies/index.cfm

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For trials on neurological disorders and stroke, visit and search the Web site sponsored by the National Institute of Neurological Disorders and Stroke of the NIH: http://www.ninds.nih.gov/funding/funding_opportunities.htm#Clinical_Trials

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CHAPTER 6. PATENTS ON HORMONE THERAPY 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.6 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 “hormone therapy” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on hormone therapy, we have not necessarily excluded nonmedical patents in this bibliography.

Patents on Hormone Therapy By performing a patent search focusing on hormone therapy, 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. 6Adapted

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 hormone therapy: •

Compositions, methods and devices for the transdermal delivery of drugs Inventor(s): Christensen; Michael S. (215 Springhouse La., Merion, PA 19066), Portman; Edward Malcolm (659 Peachtree St., Suite 224, Atlanta, GA 30308), Schmirler; Dennis Lee (2112 Baypoint La., Hartland, WI 53029) Assignee(s): none reported Patent Number: 6,214,374 Date filed: May 22, 1996 Abstract: The present invention is directed to compositions, and methods for the delivery of drugs. Devices for the transdermal delivery of drugs are also provided. Specifically, the present invention relates to hydrogel compositions comprising water and a base mixture, in which the base mixture comprises: (i) a gelling agent consisting of methycellulose or at least one natural gum, or a mixture thereof; (ii) at least one natural gum: (iii) glucose; (iv) propylparaben; (v) methyl paraben; and (vi) sodium chloride.The compositions may further comprise pectin, glycolic, alcoholic or oil-based additives, a coloring, fragrance, or other pharmaceutically acceptable additive. The compositions may further comprise substituted ureas of the formula R--NH--CO--NH.sub.2 such as butylurea. The compositions may further comprise drugs such as hormones selected from progesterone, progestin, estrogen and testosterone. Methods for the treatment of disorders responsive to hormone therapy are also provided. Excerpt(s): The present invention relates to compositions for the transdermal delivery of hormones comprising a hydrogel-forming base mixture and a skin permeation enhancer. Methods for the treatment of disorders responsive to the administration of hormones are also provided. The present invention further relates to devices for the transdermal delivery of drugs. A recent trend in the pharmaceutical industry has been the development of new drug delivery systems for both old and new drugs. Much of the current research in drug delivery technology is aimed at developing formulations and devices that improve the therapeutic effectiveness of drugs over conventional means of administration by controlling the rate, time and place of release of drugs in the body. Conventional dosage types include sublingual (under the tongue), oral (capsules, tablets, liquids), injectable, nasal and parenteral (suppository and non-oral) forms. While oral dosage forms comprise a substantial majority of all present dosage forms and offer ease of administration and low cost-per-use, they can suffer from inconvenient dosing intervals, side effects and reduced efficacy. Conventional dosage forms have disadvantages in certain patients, including unpredictable blood levels, difficult or uncomfortable administration and poor compliance. In order to maintain optimum blood levels, some conventional forms of drug delivery require frequent doses which can be difficult to remember or understand, particularly for the elderly patient. Failure to comply with a recommended drug regimen can endanger a patient's health. Web site: http://www.delphion.com/details?pn=US06214374__

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Cytochemical agents and methods for the detection of steroid hormone receptors in human tissues Inventor(s): Lee; Sin H. (53 Milan Rd., Woodbridge, CT 06525) Assignee(s): none reported Patent Number: 4,215,102 Date filed: January 5, 1979 Abstract: A cytochemical agent and method for the detection and identification of estrogen or progesterone receptor cells in carcinomas of the breast is described, involving an estrogen-protein-fluorochrome conjugate or a progesterone-proteinfluorochrome agent which is applied to an excised unfixed frozen tissue section, which is then examined for the appearance of fluorescent dye staining of the cells therein, for evaluation of potential endocrine or hormone therapy of the patient. Additional cytochemical agents and methods for the detection of other types of hormone receptor cells in various kinds of cancerous tissue are also disclosed, using sex hormones and endochrine steroid components. Excerpt(s): In recent years, the assay of the estrogen receptor (ER) characteristic in cytosol protein of tumor tissue homogenates has proved to be a useful technique in selecting patients having advanced mammary carcinoma for possible hormonal therapy. See, e.g., N Engl J Med, 291:1252-1253 (1974). Patients selected by estrogen receptor assay have been reported to show an objective remission rate of from 32% to 60% in contrast to only from 20% to 30% response for those patients selected solely by clinical criteria. See, e.g., Cancer, 39:1971-1977 (1977); Cancer Res, 35:3362-3364 (1975); Cancer, 39:2934-2947 (1977); Cancer 23:145-151 (1969) and JAMA, 172:1271-1283 (1960), respectively. However, the failure to obtain higher response rates among patients whose tumors were interpreted as positive for estrogen receptor, coupled with the fact that about 10% of those patients suffering from breast cancer with no demonstrable estrogen receptor value still responded favorably to a variety of endocrine therapies, indicate that further improvement of the existent methodology is needed for detecting and discriminating potentially hormone-responsive mammary carcinomas. The current biochemical assay methods measure the estradiol-binding capacity of the proteins in the cytosol fraction of tissue homogenates. Its results are therefore influenced by the actual size of the cancerous mass in the tissue submitted for assay, by the percentage of cancer receptor protein extractable into the cytosol, and by the proteins extractable from other non-cancerous tissue components. Consequently, variations in these factors alone can contribute to the observed wide fluctuations of the final deduced estrogen receptor values, and result in an inaccurate indication of the true physiological states of the cancer cell population. Web site: http://www.delphion.com/details?pn=US04215102__

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Male contraceptive implant Inventor(s): Moo-Young; Alfred J. (Hastings-on-Hudson, NY), Saleh; Saleh I. (Queens, NY) Assignee(s): The Population Council, Center for Biomedical Research (New York, NY) Patent Number: 5,733,565 Date filed: February 23, 1996

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Abstract: The present invention relates to implantable male contraceptive devices. An ethylene vinyl acetate copolymer based implant is described for delivery of an androgen and a system including an ethylene vinyl acetate copolymer based implant as well as a second implant are described for the administration of both androgen and a sterilitant. These implants may be used to provide contraception for men, as well as, for hormone therapy, treatment of enlarged prostate and other aliments. Excerpt(s): The present invention relates to the field of male contraception as well as the treatment of benign prostrate hypertrophy, and other conditions which can be treated by androgen or hormone therapy and to methods and apparatus regarding same. Contraception is a difficult subject under any circumstance. It is fraught with cultural and social stigma, religious implications and, most certainly, significant health concerns. This situation is only exacerbated when the subject focuses on male contraception. Despite the availability of suitable contraceptive devices, historically, society has looked to women to be responsible for contraceptive decisions and their consequences. Although health concerns over sexually transmitted diseases has made men more aware of the need to develop safe and responsible sexual habits, women still often bear the brunt of contraceptive choice. Web site: http://www.delphion.com/details?pn=US05733565__ •

Use of IGF-I for the treatment of renal insufficiencies, steriod toxicity and related indications Inventor(s): Acott; Philip D. (Halifax, CA), Crocker; John F. S. (Halifax, CA) Assignee(s): Dalhousie University (Halifax, CA) Patent Number: 6,071,880 Date filed: May 7, 1999 Abstract: In accordance with the present invention, there are provided methods for the treatment of chronic renal insufficiencies and related chronic indications in mammals, employing IGF-I as the active agent. In accordance with one embodiment of the present invention, it has been discovered that IGF-I is an effective agent for enhancing kidney development in mammals suffering from chronic organ injury. In accordance with a further embodiment of the present invention, it has been discovered that IGF-I is an effective agent for protecting prepubescent subjects, such as prepubescent mammals and neonates, from the ongoing toxicity of treatment with steroid hormones. In accordance with a still further embodiment of the present invention, it has been discovered that IGF-I is an effective agent for maintaining substantially normal growth in neonates and pre-pubescent mammals exposed to high dose steroid hormone therapy. Excerpt(s): The present invention relates to methods for the treatment of renal dysplasias and/or renal hypoplasias in non-adult subjects. In yet another aspect, the present invention relates to methods to enhance glomerular development in young mammals. In still another aspect, the present invention relates to methods to enhance kidney development in mammals suffering from chronic organ injury. In a further aspect, the present invention relates to methods to protect young subjects from the ongoing toxicity of treatment with steroid hormones. In a still further aspect, the present invention relates to methods to maintain substantially normal growth in neonates and pre-pubescent mammals exposed to high dose steroid hormone therapy. Polycystic kidney disease is a heterogenous group of disorders characterized by large kidneys with epithelial lined cysts along the nephron collecting ducts of the affected kidneys. In all

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types of cystic kidney disease, the enlargement of the cyst wall is associated with hyperplasia of renal epithelium. There are several examples of genetic predisposition to cystic disease, with the most common forms of human polycystic kidney disease (PKD) being genetically transmitted as either an autosomal dominant trait or an autosomal recessive trait. There are also several forms of acquired polycystic kidney disease. Acquired lesions are caused by broad categories of agents, such as teratogens (e.g., diphenylamine and phthalates), agents affecting metanephric development (e.g., steroid hormones such as glucocorticoids), and as a consequence of loss of renal mass (as seen in end-stage renal disease). Even in kindreds with a defined genetic mutation, there is broad expression of the clinical phenotype. An example of this is a family with autosomal recessive PKD in several siblings, where the onset of renal failure was variable in the child and adolescent years. It is also well established that autosomal dominant PKD is asymptomatic in half of the kindred who are genetically affected, while approximately 1/6 go to renal failure. Moreover, the genetic trait does not discriminate the phenotypic variation of gender. The observation that the genetics are only one part of the clinical phenotype of PKD has created interest in looking at the pathophysiology of cystic disease and progression in the hope of finding modifying agents. Currently, however, there is no effective treatment for Polycystic Kidney ill Disease (PKD), one of the three leading causes of end stage renal failure in humans (Canadian Organ Replacement Register; p. 95 [1990]). Although PKD simulates Mendelian inheritance, there is evidence that phenotypic expression of PKD involves genetic heterogeneity and multifactorial inheritance, including nongenetic factors. Web site: http://www.delphion.com/details?pn=US06071880__

Patent Applications on Hormone Therapy As of December 2000, U.S. patent applications are open to public viewing.7 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 hormone therapy: •

Dosage forms and methods for oral delivery of progesterone Inventor(s): Ho, Thomas Chun; (Irvine, CA), Hsia, David Chung; (Irvine, CA), Tan, Domingo Yap; (Irvine, CA), Weihmuller, Fredric C.; (Huntington Beach, CA) Correspondence: Foley And Lardner; Suite 500; 3000 K Street NW; Washington; DC; 20007; US Patent Application Number: 20030143276 Date filed: February 24, 2003 Abstract: Oral progesterone unit dosage forms comprising micronized progesterone and a solid polymeric carrier are provided. The dosage forms, upon oral administration, provide a therapeutically effective blood level of progesterone to a subject. The therapeutically effective blood level of progesterone may range from about 0.1 ng/ml to about 400 ng/ml. The dosage forms can be prepared for immediate as well as sustained release. The oral progesterone dosage form can be combined with an estrogen dosage form to provide combination hormone therapy.

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

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Excerpt(s): This application is a continuation of pending U.S. application Ser. No. 09/473,548, filed Dec. 28, 1999 the disclosure of which is hereby incorporated by reference in its entirety. This invention relates to oral dosage forms of hormones and methods for their delivery to subjects needing hormone therapy. Agnus et al., U.S. Pat. No. 6,086,916, col. 1, line 56- col. 2, line 4, discusses Gram [Novo Nordisk]WO 95/05807 as "describ[ing] tablets containing progesterone and a polyethylene glycol, as well as an excipient chosen from the group containing starches, starch-containing components, modified starches, celluloses, modified celluloses, pectins and tragacanth. [T]he presence of polyethylene glycol and of the excipient in the tablets results in a favourable effect on the bio-availability of orally administered progesterone. * * * [T]he tablets * * * contain high percentages of excipients." Gram's Abstract states that she provides an oral progeseterone that "may, conveniently, contain a PEG, and a further excipient selected from the group comprising a starch, a cellulose, pecting, and tragacanth." The polyethylene glycols are refrred to as "liquid or solid polymers". Page 7, lines 20-22. Examples with progesterone and estradiol include maize starch, lactose, polyethylene glycol 6000, croscarmellose sodium, magnesium stearate and taclum powder. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Growth hormone therapy and related methods and pharmaceutical compositions Inventor(s): Fahy, Gregory M.; (Gaithersburg, MD) Correspondence: Price Heneveld Cooper Dewitt & Litton; 695 Kenmoor, S.E.; P O Box 2567; Grand Rapids; MI; 49501; US Patent Application Number: 20020016286 Date filed: August 20, 2001 Abstract: Human growth hormone therapy and thynic regeneration are effected by the generally simultaneous administration of one of human growth hormone, its analogs, precursors, metabolites, releasers or mixtures thereof in combination with one of DHEA, its precursors, releasers, analogs, metabolites or combinations thereof. Excerpt(s): The present invention relates to human growth hormone therapy and to the cure of human disease through organ and tissue transplantation. The present invention includes a method for regenerating the human thymus to allow intrathymic transplantation and thereby the elimination of organ and tissue rejection. There are two variations of this method, one that employs growth hormone and one that employs agent that can substitute for growth hormone's thymus-regenerating effects. The former method has wide applicability beyond the transplantation of tissues and organs, because it involves the elimination of the most important side effects of growth hormone. Human growth hormone (HGH) has been recognized as a treatment for children of short stature or with renal failure, and has been a safe and effective treatment in most cases, but there are several reports that such children often experience hyperinsulinemia as a result of HGH administration. Further, HGH has been considered as a powerful approach to the treatment of human aging, but its widespread use is inhibited by its serious side effects, the most important of which is elevation of fasting and glucosestimulated insulin levels, a phenomenon that is known to be a risk factor for atherosclerosis and cardiovascular disease. Arginine, an HGH releaser, has therapeutic effects in its own right, but has the same drawback of elevating blood insulin levels. The invention described here permits HGH therapy to be administered with no elevation in blood levels of insulin. Much has been written of late about the growing excitement of anti-aging (gerolytic) therapies, including hormone replacement therapy with

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dehydroepiandrosterone (DHEA), melatonin, sex hormones, thyroid hormone, cordsol, or human growth hormone. Of these, the work of Rudman has attracted the most attention because of his statement that administration of human growth hormone (HGH) produced the same effects as the reversal of 20 years of aging. Rudman and others have, in fact, amassed an impressive body of evidence indicating that it is the loss of HGH with age that is responsible for much of the human aging process, including atrophy of internal body organs, thinning of the skin, slowing of cell division, weakening of muscles and bones, and accumulation of body fat. Even immune system decline with age seems largely dependent on loss of HGH. Furthermore, GH administration to animals produces a radical increase in longevity. On the other hand, Marcus et al. have shown the down side of HGH: given at the minimum doses used in Marcus' study, equivalent to the doses used by Rudman, HGH produced dramatic and disturbing rises in fasting and stimulated serum insulin levels. The administration of HGH is known to decrease the body's sensitivity (i.e., responsiveness) to insulin, thus causing a compensating rise in pancreatic insulin output and therefore in serum insulin levels; yet paradoxically, falling HGH levels in aging humans are accompanied by increasing serum insulin levels. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Hormone therapy methods and hormone products for abating coronary artery blockage Inventor(s): Chein, Edmund Y.M.; (Palm Springs, CA) Correspondence: Patrick F. Lorig, P.C.; Bright & Lorig, P.C.; 633 West Fifth Street, Suite 3330; Los Angeles; CA; 90071; US Patent Application Number: 20020065273 Date filed: February 5, 2000 Abstract: Methods for abating coronary artery blockage in human subjects include administering a combination of natural hormones including human growth hormone with sufficient T3 thyroid supplement to maintain the body temperature of the subject at or above 97.6.degree. F. upon awakening and at 98.7.degree. F. or higher during afternoon hours. Testosterone, if any, administered to male subjects is in natural, gel form. Excerpt(s): This invention relates to methods and products to abate coronary artery blockage in men and in women. These methods include administering a combination of natural hormones, including human growth hormone or recombinant human growth hormone, one or more sex hormones, such as testosterone, estrogen or progesterone and other naturally occurring hormones, as appropriate. The methods and products of this invention are disclosed in part in U.S. Pat. No. 5,855,920, issued Jan. 5, 1999, entitled TOTAL HORMONE REPLACEMENT THERAPY. The entire text of the '920 patent is incorporated herein by this reference. However, in abating coronary artery blockage in men and women, the methods of this invention additionally call for administering sufficient T3 thyroid supplement to maintain the body temperature of males and females with such blockage above about 97.6.degree. F. upon awakening, and is in the range of about 98.7.degree. F. to about 99.0.degree. F. during the afternoon hours. In addition, in treating males with coronary artery blockage, and with below optimal testosterone levels, these methods call for administering natural testosterone in gel form, preferably applied topically to under arm pits. In treating a human male or female subject who has blockage of coronary arteries, a treating physician preferably obtains

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the subject's records, including, where available, MRI, CAT scan, angiogram and all other pictorial and visual documentation of the blockage. The treating physician then measures the subject's total cholesterol, HDL, LDL, and triglyceride levels, and the subject's hormones in terms of growth hormone level as reflected through IGF-1 level, melatonin level, thyroid hormone level, thymus hormone level, adrenal hormone of DHEA level and pregnenolone level, and the subject's sex hormone(s) level (in males, testosterone; in females, progesterone and estrogen). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Nonsteroidal gestagens Inventor(s): Fritzemeier, Karl-Heinrich; (Berlin, DE), Heinrich, Nikolaus; (Berlin, DE), Krattenmacher, Rolf; (Berlin, DE), Lehmann, Manfred; (Berlin, DE), Muhn, Hans-Peter; (Berlin, DE), Schoellkopf, Klaus; (Berlin, DE), Strehlke, Peter; (Berlin, DE) Correspondence: Millen, White, Zelano & Branigan, P.C.; 2200 Clarendon BLVD.; Suite 1400; Arlington; VA; 22201; US Patent Application Number: 20020016365 Date filed: July 27, 2001 Abstract: This invention describes the new, nonsteroidal gestagens of general formula I 1in whichA, B, Ar.sup.1, R.sup.1, R.sup.2 and R.sup.3 have the meanings that are indicated in more detail in the description. The new compounds show a very great affinity to the gestagen receptor. They can be used alone or in combination with estrogens in contraceptive preparations. In addition, they can be used for treating endometriosis. Together with estrogens, they can also be used in preparations for treating gynecological disorders, for treating premenstrual symptoms and for substitution therapy.Based on the androgenic action, they can also be used for male birth control, male HRT and hormone therapy and for treating andrological disease agents. Excerpt(s): This invention relates to nonsteroidal compounds, which have a high gestagenic activity. In addition to a large number of steroid compounds with gestagenic action, gestagens that are not steroids are also known (for example from EP 0 253 500 B1 and WO 94/01412, cf. J. Med. Chem. 38 (1995) 4878). in which R.sup.9 and R.sup.10 are the same or different and mean a cyano group, a nitro group, a halogen atom, a C.sub.1C.sub.5 alkyl group, a C.sub.1-C.sub.5 alkoxy group, a partially or completely fluorinated C.sub.1-C.sub.5 alkyl group, a C.sub.1-C.sub.5 alkylthio group, a C.sub.1C.sub.5 alkylsulfinyl group or a C.sub.1-C.sub.5 alkylsulfonyl group, and if B stands for a CH.sub.2 group, the physiologically compatible salts of the compounds of general formula I with acids. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Patient compliance and monitoring system Inventor(s): Leonard, Thomas W.; (Wilmington, NC), Waldon, R. Forrest; (Wilmington, NC) Correspondence: Allen R. Baum; Burns, Doane, Swecker & Matthis, L.L.P.; P. O. Box 1404; Alexandria; VA; 22313-1404; US Patent Application Number: 20030036923 Date filed: May 18, 2001 Abstract: This invention is directed to methods and systems for monitoring compliance with or effectiveness of hormone replacement therapy. The methods and systems of the invention provide an efficient means of communication between medical professionals and patients for between visit monitoring of patient compliance with a prescribed hormone therapy and the effectiveness of the treatment recommended. Excerpt(s): The present invention relates to methods of monitoring patient symptoms, side effects and compliance with administration of prescribed therapeutic agents that are prophylactic or used to treat slow onset or chronic conditions. The present invention further provides systems for remotely assessing patient symptoms, side effects, and compliance with chronic therapeutic agents. There are significant problems with patient compliance monitoring and communication in prophylactic therapies or in the treatment of slow onset conditions or diseases or chronic conditions, such as osteoporosis, vasomotor symptoms associated with menopause, vulvar/vagina atrophy associated with menopause, cardiovascular prophylaxis, neurodegenerative disease and hypertension. Symptoms resulting from these types of conditions may be difficult for the patient to accurately describe in a short office visit with medical professionals and may change as therapy is ongoing. These changes may require a review of the patient's symptoms over time to ascertain therapy effectiveness and side effects profiles. In addition, the symptoms may be difficult for medical professionals to adequately detect, diagnose, and address in the small amount of time devoted to each patient during an office visit. In addition to addressing patient symptoms and side effects in therapies for prophylaxis, in slow onset diseases or other conditions, there is often a problem with patient compliance with the administration of recommended or prescribed therapeutic agents. In some cases the patients may discontinue therapy because acute symptoms subside. Others may stop therapy because side effects of the therapy become more pronounced or troubling than the symptoms of the disease or condition. Additionally patients may discontinue therapy because of a perceived lack of benefit or overexaggeration of risk related to therapies. In many cases patients may take the therapy sporadically or not as regularly as recommended for optimum benefit. The patient's physician may not become aware of cessation of therapy or sporadic continuation of therapy in time to address problems that may result and encourage compliance, or modify the therapy to optimize results. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Selective androgen receptor modulators and methods of use thereof Inventor(s): Dalton, James T.; (Columbus, OH), He, Yali; (Florence, SC), Miller, Duane D.; (Germantown, TN), Yin, Donghua; (Columbus, OH) Correspondence: Eitan, Pearl, Latzer & Cohen-zedek; One Crystal Park, Suite 210; 2011 Crystal Drive; Arlington; VA; 22202-3709; US Patent Application Number: 20020099036 Date filed: August 23, 2001 Abstract: The present invention relates to a novel class of androgen receptor targeting agents (ARTA) which demonstrate androgenic and anabolic activity of a nonsteroidal ligand for the androgen receptor. The agents define a new subclass of compounds which are selective androgen receptor modulators (SARM) which are useful for male hormone therapy such as oral testosterone replacement therapy, treating prostate cancer, imaging prostate cancer. Excerpt(s): This Application claims the benefit of U.S. Ser. No. 09/644,970, filed Aug. 24, 2000 and claims priority of U.S. Ser. No. 601300,083, filed Jun. 25, 2001, which are hereby incorporated by reference. The androgen receptor ("AR") is a ligand-activated transcriptional regulatory protein that mediates induction of male sexual development and function through its activity with endogenous androgens. Androgens are generally known as the male sex hormones. The androgenic hormones are steroids which are produced in the body by the testis and the cortex of the adrenal gland, or synthesized in the laboratory. Androgenic steroids play an important role in many physiologic processes, including the development and maintenance of male sexual characteristics such as muscle and bone mass, prostate growth, spermatogenesis, and the male hair pattern (Matsumoto, Endocrinol. Met. Clin. N. Am. 23:857-75 (1994)). The endogenous steroidal androgens include testosterone and dihydrotestosterone ("DHT"). Testosterone is the principal steroid secreted by the testes and is the primary circulating androgen found in the plasma of males. Testosterone is converted to DHT by the enzyme 5 alphareductase in many peripheral tissues, DHT is thus thought to serve as the intracellular mediator for most androgen actions (Zhou, et al., Molec. Endocrinol. 9:208-18 (1995))Other steroidal androgens include esters of testosterone, such as the cypionate, propionate, phenylpropionate, cyclopentylpropionate, isocarporate, enanthate, and decanoate esters, and other synthetic androgens such as 7-Methyl-Nortestosterone ("MENT") and its acetate ester (Sundaram et al., "7 Alpha-MethylNortestosterone(MENT): The Optimal Androgen For Male Contraception," Ann. Med., 25:199-205 (1993) ("Sundaram")). Because the AR is involved in male sexual development and function, the AR is a likely target for effecting male contraception or other forms of hormone replacement therapy. Worldwide population growth and social awareness of family planning have stimulated a great deal of research in contraception. Contraception is a difficult subject under any circumstance. It is fraught with cultural and social stigma, religious implications, and, most certainly, significant health concerns. This situation is only exacerbated when the subject focuses on male contraception. Despite the availability of suitable contraceptive to devices, historically, society has looked to women to be responsible for contraceptive decisions and their consequences. Although health concerns over sexually transmitted diseases has made men more aware of the need to develop safe and responsible sexual habits, women still often bear the brunt of contraceptive choice. Women have a number of choices from temporary mechanical devices such as sponges and diaphragms to temporary chemical devices such as spermicides. Women also have at their disposal more permanent options such as physical devices like IUDs and cervical caps as well as more permanent

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chemical treatments such as birth control pills and subcutaneous implants. However, to date, the only options available for men include the use of condoms and a vasectomy. Condom use, however is not favored by many men because of the reduced sexual sensitivity, the interruption in sexual spontaneity, and the significant possibility of pregnancy caused by breakage or misuse. Vasectomies are also not favored. If more convenient methods of birth control were available to men, particularly long term methods which required no preparative activity immediately prior to a sexual act, such methods could significantly increase the likelihood that men would take more responsibility for contraception. 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 hormone therapy, 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 “hormone therapy” (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 hormone therapy. You can also use this procedure to view pending patent applications concerning hormone therapy. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.

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CHAPTER 7. BOOKS ON HORMONE THERAPY Overview This chapter provides bibliographic book references relating to hormone therapy. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on hormone therapy 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 “hormone therapy” (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 hormone therapy: •

Understanding Your Prostate Problems Source: Woollahra, New South Wales, Australia: Health Books, Gore and Osment Publications. 1993. 64 p. Contact: Available from Health Books, Gore and Osment Publications, Private Box 427, 150 Queen Street, Woollahra, NSW 2025, Australia. (02) 361-5244. Fax (02) 360-7558. PRICE: $9.95 (as of 1995). ISBN: 1875531459. Summary: This health education book is designed to help readers understand the function of the prostate, prostatic diseases, and treatment options for prostate problems. Eleven chapters cover topics including the anatomy and physiology of the prostate; prostatic enlargement; prostate cancer; other prostate problems, including prostatitis, urethral stricture, and urinary stones; diagnostic tests used to confirm or screen for prostate problems; prostate surgery; other types of treatment, include drug therapy,

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laser treatments, transurethral resection, stents, catheters, hyperthermia, and balloon dilatation; radiotherapy for prostate cancer; hormone therapy for prostate cancer; chemotherapy for prostate cancer; and suggestions for patient self-care. The book is written in easy-to-read language, with simple illustrations; a brief glossary concludes the volume. •

Managing Osteogenesis Imperfecta: A Medical Manual Source: Gaithersburg, MD: Osteogenesis Imperfecta Foundation (OIF). 1997. 220 p. Contact: Available from Osteogenesis Imperfecta Foundation. 804 West Diamond Avenue, Suite 210, Gaithersburg, MD 20878. (800) 981-2663 or (301) 947-0083. Fax (301) 947-0456. Website: www.oif.org. PRICE: $25.00 plus shipping and handling. Summary: This manual for health professionals, people who have osteogenesis imperfecta (OI), and parents of children who have OI provides information on its medical management. Chapter one serves as an introduction, focusing on the genetics of OI, its signs and symptoms, anesthetic care, child abuse, and recommendations for checkups. The next chapter provides information on normal bone development, bone in OI, and treatment. Chapters three and four focus on imaging methods and characteristics. Chapter five describes treating fractures and focuses on cast application, care, and removal. This is followed by a chapter on the surgical management of with intramedullary rod fixation. Chapter seven examines the relationship between OI and osteoporosis, while chapter eight details the aspects of a total fitness program, including aerobic conditioning, muscle strengthening and stretching, and skill- related activities. Topics discussed in chapters nine through 11 include the intrapartum management of a patient with OI, prenatal and clinical diagnosis, and care of a newborn with severe OI. Chapters on developmental and educational issues, the use of growth hormone therapy, and obstacles to motor performance and interventions to minimize or compensate for them follow. Chapters 15 through 19 discuss dental care, cardiovascular manifestations and their treatment, care of the feet, evaluation and treatment of hearing loss, and osteoarthritis. The final two chapters highlight some of the psychological ramifications of having a person with OI in a family and discuss types of pain and pain management. 5 appendices, 4 tables, and numerous figures and references.

Book Summaries: Online Booksellers Commercial Internet-based booksellers, such as Amazon.com and Barnes&Noble.com, offer summaries which have been supplied by each title’s publisher. Some summaries also include customer reviews. Your local bookseller may have access to in-house and commercial databases that index all published books (e.g. Books in Print®). IMPORTANT NOTE: Online booksellers typically produce search results for medical and non-medical books. When searching for “hormone therapy” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “hormone therapy” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “hormone therapy” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •

A Woman Doctor's Guide to Hormone Therapy: How to Choose What's Right for You by Nananda Francette, Md. Col (1997); ISBN: 1886284032; http://www.amazon.com/exec/obidos/ASIN/1886284032/icongroupinterna

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Challenges in Growth Hormone Therapy by John P. Monson (Editor); ISBN: 0632051647; http://www.amazon.com/exec/obidos/ASIN/0632051647/icongroupinterna

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Current Indications for Growth Hormone Therapy, Endocrine Development by Peter C. Hindmarsh (Editor) (1999); ISBN: 380556757X; http://www.amazon.com/exec/obidos/ASIN/380556757X/icongroupinterna

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Dr Love's Hormone Therapy by M. D. Susan M. Love (1999); ISBN: 0609000179; http://www.amazon.com/exec/obidos/ASIN/0609000179/icongroupinterna

•

Growth Hormone Therapy in Turner Syndrome (Journal, Vol. 39, Supplement 2, 1993: Hormone Research) by R. G. Thompson (Editor); ISBN: 3805557957; http://www.amazon.com/exec/obidos/ASIN/3805557957/icongroupinterna

•

Hormone Therapy by Furr (1997); ISBN: 0721639607; http://www.amazon.com/exec/obidos/ASIN/0721639607/icongroupinterna

•

Hormone Therapy and Cardiovascular Dynamics - pocketbook by Carolyn Webb, Peter Collins (1998); ISBN: 1853174092; http://www.amazon.com/exec/obidos/ASIN/1853174092/icongroupinterna

•

Hormone Therapy and the Brain: A Clinical Perspective on the Role of Estrogen by Victor W. Henderson, Victor Henderson; ISBN: 1850700788; http://www.amazon.com/exec/obidos/ASIN/1850700788/icongroupinterna

•

Hormone Therapy in Breast and Prostate Cancer by V. Craig Jordan (Editor), et al; ISBN: 0896036731; http://www.amazon.com/exec/obidos/ASIN/0896036731/icongroupinterna

•

Hormone Therapy of Acne: Clinical and Experimental Principles by Doris Fanta (1980); ISBN: 0387815864; http://www.amazon.com/exec/obidos/ASIN/0387815864/icongroupinterna

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Hormone therapy of the menopause and aging by Helen Z. Jern; ISBN: 0398027447; http://www.amazon.com/exec/obidos/ASIN/0398027447/icongroupinterna

•

New Directions in Growth Hormone Therapy by Michael B. Ranke (Editor); ISBN: 3920671147; http://www.amazon.com/exec/obidos/ASIN/3920671147/icongroupinterna

•

Paradise Regaining in the New Millennium: The Way Forward Through the Natural Hormone Therapy: An Anthology by Members of the Alice Shepherd Foundation by Arthur Hayes (Editor), et al (1997); ISBN: 1857563166; http://www.amazon.com/exec/obidos/ASIN/1857563166/icongroupinterna

•

Progress in Growth Hormone Therapy: 5 Years of Kigs by Michael B. Ranke (Editor), Rolf Gunnarsson (Editor); ISBN: 3920671112; http://www.amazon.com/exec/obidos/ASIN/3920671112/icongroupinterna

•

The Estrogen Alternative: Natural Hormone Therapy with Botanical Progesterone by Raquel Martin, Judi Gerstung (Contributor); ISBN: 089281893X; http://www.amazon.com/exec/obidos/ASIN/089281893X/icongroupinterna

•

The Facts of Hormone Therapy for Menopausal Women by David W. Sturdee; ISBN: 185070807X; http://www.amazon.com/exec/obidos/ASIN/185070807X/icongroupinterna

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The Menopause, Hormone Therapy, & Women's Health (1992); ISBN: 1568060424; http://www.amazon.com/exec/obidos/ASIN/1568060424/icongroupinterna

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The Menopause, Hormone Therapy, and Women's Health (Background Paper) by 52003012847 (1992); ISBN: 0160379121; http://www.amazon.com/exec/obidos/ASIN/0160379121/icongroupinterna

•

The Testosterone Solution: Increase Your Energy and Vigor With Male Hormone Therapy by Aubrey M. Hill; ISBN: 0761510222; http://www.amazon.com/exec/obidos/ASIN/0761510222/icongroupinterna

The National Library of Medicine Book Index The National Library of Medicine at the National Institutes of Health has a massive database of books published on healthcare and biomedicine. Go to the following Internet site, http://locatorplus.gov/, and then select “Search LOCATORplus.” Once you are in the search area, simply type “hormone therapy” (or synonyms) into the search box, and select “books only.” From there, results can be sorted by publication date, author, or relevance. The following was recently catalogued by the National Library of Medicine:8 •

A clinical guide; male sex hormone therapy. Author: Schering Corporation. Medical Research Division.; Year: 2002; [Bloomfield, N. J.] Medical research division, the Schering corporation, 1941

•

Practical hormone therapy; a manual of organotherapy for general practitioners. Author: Harrower, Henry R. (Henry Robert),; Year: 2003; New York, Hoeber, 1914

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

Fetal Lung Development Source: in Reece, E.A.; Coustan, D.R., eds. Diabetes Mellitus in Pregnancy. 2nd ed. New York, NY: Churchill Livingstone. 1995. p. 93-106. Contact: Available from Churchill Livingstone. 300 Lighting Way, Secaucus, NJ 07094. (800) 553-5426. PRICE: $92.00. ISBN: 0443089795.

8

In addition to LOCATORPlus, in collaboration with authors and publishers, the National Center for Biotechnology Information (NCBI) is currently adapting biomedical books for the Web. The books may be accessed in two ways: (1) by searching directly using any search term or phrase (in the same way as the bibliographic database PubMed), or (2) by following the links to PubMed abstracts. Each PubMed abstract has a "Books" button that displays a facsimile of the abstract in which some phrases are hypertext links. These phrases are also found in the books available at NCBI. Click on hyperlinked results in the list of books in which the phrase is found. Currently, the majority of the links are between the books and PubMed. In the future, more links will be created between the books and other types of information, such as gene and protein sequences and macromolecular structures. See http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Books.

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Summary: This chapter, from a medical textbook on diabetes mellitus in pregnancy, discusses fetal lung development. The authors stress that in pregnancy complicated by diabetes, abnormalities in the metabolic and hormonal environment result in delayed fetal lung maturation. Topics include the physiology of fetal lung development; respiratory distress syndrome (RDS), its diagnosis, and risk factors; amniotic fluid indices of lung maturity; diabetic pregnancy and fetal lung maturity, including the mechanisms leading to RDS, how hormonal changes delay lung maturity, how insulin and hyperglycemia may affect fetal lung maturation, White's classification system and its role in assessing RDS risk, how maternal glycemic control affects RDS risk, and recommendations for clinical management of these pregnancies. The authors note that, with the advent of methods to analyze surfactant components and deficiencies, it is now possible to predict the risk of respiratory distress syndrome (RDS) in infants of mothers with diabetes (IDMs). The authors conclude that improvements in obstetric management aimed at controlling maternal glycemia and eliminating metabolic and hormonal abnormalities, as well as efforts to promote vaginal delivery with mature amniotic fluid fetal lung profiles, have resulted in a dramatic decrease in the incidence of RDS among IDMs. Continued advances, including hormone therapy to accelerate fetal lung maturation when delivery is indicated despite known fetal lung immaturity, are likely to further reduce this risk. 3 figures. 4 tables. 81 references. •

Chapter 39-A: Pediatric Rheumatic Diseases: Special Considerations Source: in Klippel, J.H., et al., eds. Primer on the Rheumatic Diseases. 12th ed. Atlanta, GA: Arthritis Foundation. 2001. p. 529-534. Contact: Available from Arthritis Foundation. P.O. Box 1616, Alpharetta, GA 300091616. (800) 207-8633. Fax (credit card orders only) (770) 442-9742. Website: www.arthritis.org. PRICE: $69.95 plus shipping and handling. ISBN: 0912423293. Summary: This section of a chapter on pediatric rheumatic diseases provides health professionals with information on issues that relate to the growth and development of the child with a rheumatic disease. The chapter begins with guidelines on performing a physical examination on infants and toddlers, school aged children, and adolescents. This is followed by a discussion of the impact of juvenile rheumatoid arthritis (JRA) on the growth of a child. Local growth disturbances occur as a result of inflammation. Common sites affected by JRA include the knee, the temporomandibular joint, the wrist, and the vertebrae. A child with JRA is at increased risk for osteopenia. Adequate nutrition, both caloric and protein, is needed for optimizing growth in children with JRA. The levels of various endocrine hormones have been found to correlate with disease activity in children with JRA, and growth hormone therapy has been found to be beneficial in some patients. In addition, the chapter identifies factors affecting patient adherence to recommended therapeutic regimens and suggests educational, organizational, and behavioral strategies for improving adherence. The chapter concludes with a discussion of psychosocial and educational issues affecting children with a chronic disease. 2 tables and 30 references.

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CHAPTER 8. MULTIMEDIA ON HORMONE THERAPY Overview In this chapter, we show you how to keep current on multimedia sources of information on hormone therapy. 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.

Bibliography: Multimedia on Hormone Therapy The National Library of Medicine is a rich source of information on healthcare-related multimedia productions including slides, computer software, and databases. To access the multimedia database, go to the following Web site: http://locatorplus.gov/. Select “Search LOCATORplus.” Once in the search area, simply type in hormone therapy (or synonyms). Then, in the option box provided below the search box, select “Audiovisuals and Computer Files.” From there, you can choose to sort results by publication date, author, or relevance. The following multimedia has been indexed on hormone therapy: •

Hormone therapy [videorecording]: fountain of youth Source: a presentation of Films for the Humanities & Sciences, ABC News Productions; Year: 1999; Format: Videorecording; Princeton, N.J.: Films for the Humanities and Sciences, c1999

•

Hormone therapy in young women with irregular menses [videorecording] Source: with Michelle P. Warren; Year: 1986; Format: Videorecording; Secaucus, N.J.: Network for Continuing Medical Education, 1986

•

Postmenopausal hormone therapy [videorecording]: weighing the benefits and risks Source: Leon Speroff; Year: 1996; Format: Videorecording; Secaucus, N.J.: Network for Continuing Medical Education, c1996

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CHAPTER 9. PERIODICALS AND NEWS ON HORMONE THERAPY Overview In this chapter, we suggest a number of news sources and present various periodicals that cover hormone therapy.

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

Tibolone may be an alternative to hormone therapy in postmenopausal women Source: Reuters Industry Breifing Date: October 21, 2003

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Hormone therapy raises stroke risk for some women Source: Reuters Health eLine Date: October 20, 2003

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Hormone therapy risks outweigh bone benefits Source: Reuters Health eLine Date: September 30, 2003

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FDA launches hormone therapy campaign Source: Reuters Health eLine Date: September 10, 2003

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UK's NICE restricts growth hormone therapy in adults Source: Reuters Industry Breifing Date: August 27, 2003

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NICE restricts growth hormone therapy in UK adults Source: Reuters Medical News Date: August 27, 2003

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Hormone therapy fails to reverse bone loss in dancers with amenorrhea Source: Reuters Industry Breifing Date: August 18, 2003

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More doubts cast on hormone therapy benefits Source: Reuters Health eLine Date: August 07, 2003

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Prostate cancer survival improved with whole-pelvic radiation plus hormone therapy Source: Reuters Medical News Date: June 13, 2003

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U.S. studies: more bad news for hormone therapy Source: Reuters Health eLine Date: May 27, 2003

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Hormone therapy ups urinary incontinence risk Source: Reuters Health eLine Date: April 30, 2003

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FDA questions hormone therapy for hot flashes Source: Reuters Health eLine Date: April 10, 2003

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No quality-of-life benefit seen for hormone therapy Source: Reuters Health eLine Date: March 18, 2003

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Hormone therapy not recommended for short teens with normal puberty Source: Reuters Medical News Date: March 07, 2003

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UK study finds hormone therapy won't protect heart Source: Reuters Health eLine Date: February 26, 2003

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Hormone therapy found riskier for diabetic women Source: Reuters Health eLine Date: February 21, 2003

Periodicals and News

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Combination hormone therapy increases women's stroke risk, even in first year Source: Reuters Industry Breifing Date: February 14, 2003

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FDA: Hormone therapy drug labels to change Source: Reuters Health eLine Date: January 08, 2003

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Hormone therapy before prostatectomy appropriate for stage T3 prostate cancer Source: Reuters Medical News Date: December 17, 2002

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Hormone therapy common among older UK women Source: Reuters Health eLine Date: December 11, 2002

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Hormone therapy a potential male contraceptive Source: Reuters Health eLine Date: December 05, 2002

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Hormone therapy, vitamins don't help heart: study Source: Reuters Health eLine Date: November 19, 2002

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Growth hormone therapy in the elderly: not ready for prime tiMen Source: Reuters Industry Breifing Date: November 12, 2002

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Studies of hormone therapy to continue: NIH Source: Reuters Industry Breifing Date: October 24, 2002

•

Some studies of hormone therapy to continue: NIH Source: Reuters Health eLine Date: October 24, 2002

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Hormone therapy before radical prostatectomy offers no benefit Source: Reuters Medical News Date: October 08, 2002

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Hormone therapy shows promise as male contraceptive Source: Reuters Health eLine Date: September 16, 2002

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Growth hormone therapy may have limited benefits in short children Source: Reuters Industry Breifing Date: September 13, 2002

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Drug maker amends hormone therapy prescribing info Source: Reuters Health eLine Date: September 04, 2002

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US officials to reassess value of hormone therapy Source: Reuters Health eLine Date: August 14, 2002

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Growth hormone therapy does not increase cancer recurrence risk Source: Reuters Industry Breifing Date: August 05, 2002

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Estrogen hormone therapy ups risk of ovarian cancer Source: Reuters Health eLine Date: July 16, 2002

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Britain urges caution after hormone therapy alert Source: Reuters Health eLine Date: July 10, 2002

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King completes acquisition of Johnson Johnson hormone therapy product Source: Reuters Industry Breifing Date: May 29, 2002

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NICE backs human growth hormone therapy for licensed indications Source: Reuters Industry Breifing Date: May 22, 2002 The NIH

Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine. Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name. Market Wire Market Wire is more focused on technology than the other wires. To browse the latest press releases by topic, such as alternative medicine, biotechnology, fitness, healthcare, legal, nutrition, and pharmaceuticals, access Market Wire’s Medical/Health channel at http://www.marketwire.com/mw/release_index?channel=MedicalHealth. Or simply go to Market Wire’s home page at http://www.marketwire.com/mw/home, type “hormone therapy” (or synonyms) into the search box, and click on “Search News.” As this service is technology oriented, you may wish to use it when searching for press releases covering diagnostic procedures or tests. Search Engines Medical news is also available in the news sections of commercial Internet search engines. See the health news page at Yahoo (http://dir.yahoo.com/Health/News_and_Media/), or you can use this Web site’s general news search page at http://news.yahoo.com/. Type in “hormone therapy” (or synonyms). If you know the name of a company that is relevant to hormone therapy, you can go to any stock trading Web site (such as

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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 “hormone therapy” (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 “hormone therapy” (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 hormone therapy: •

The Female Triad: Are You at Risk? Source: Weight Control Digest. 7(4):645-646; July/Aug 1997. Contact: Weight Control Digest, 1555 W. Mockingbird Lane, Suite 203, Dallas, TX 75235. (800) 736-7323. Summary: This article discusses what the author terms the 'Female Athlete Triad' or the cluster of eating disorders, amenorrhea, and bone loss. Steen says that female athletes, especially in certain 'appearance' sports such as gymnastics, ballet, and figure skating are at risk for developing this triad, due to the emphasis on physical appearance in these sports. Steen suggests such interventions as increased caloric intake, decreased physical activity, and, in extreme cases, hormone therapy. However, she says that lifestyle interventions are preferable.

•

Weight Gain in Menopausal Years Source: Healthy Weight Journal. 8(4):69-70; July/August 1994. Contact: Healthy Living Institute, 402 S. 14th St., Hettinger, ND 58639. (701) 567-2645. Summary: This article looks at weight gain during the menopausal years. This is considered a major concern for women and the health care professionals who care for them. The results of a study of weight increase among menopausal women at the University of Pittsburgh is summarized. The study showed a weight gain was highly related to increase and heart disease risk factors. Large weight increases for most women in this study occurred between the ages of 42 and 53. Hormone therapy added slightly to the change of weight gain in this population. Those with the lowest exercise levels gained the most weight.

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Academic Periodicals covering Hormone Therapy Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to hormone therapy. In addition to these sources, you can search for articles covering hormone therapy that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”

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CHAPTER 10. RESEARCHING MEDICATIONS Overview While a number of hard copy or CD-ROM resources are available for researching medications, a more flexible method is to use Internet-based databases. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.

U.S. Pharmacopeia Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications recommended for hormone therapy. One such source is the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the U.S. Pharmacopeia (USP). Today, the USP is a non-profit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at http://www.usp.org/. The USP currently provides standards for over 3,700 medications. The resulting USP DI® Advice for the Patient® can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database, located at http://www.fda.gov/cder/da/da.htm. While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopeia (USP). Below, we have compiled a list of medications associated with hormone therapy. If you would like more information on a particular medication, the provided hyperlinks will direct you to ample documentation (e.g. typical dosage, side effects, drug-interaction risks, etc.).

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The following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to hormone therapy: Conjugated Estrogens and Medroxyprogesterone for Ovarian Hormone Therapy (Oht) •

Systemic - U.S. Brands: Note: http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/209441.html

Estrogens •

Systemic - U.S. Brands: Alora; Aquest; Climara; Clinagen LA 40; Delestrogen; depGynogen; Depo-Estradiol; Depogen; Dioval 40; Dioval XX; Dura-Estrin; Duragen-20; E-Cypionate; Estinyl; Estrace; Estraderm; Estragyn 5; Estragyn LA 5; Estra-L 40; Estratab; Estro-A; Estro-Cyp; Estro http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202226.html

Estrogens and Progestins (Ovarian Hormone Therapy) •

Systemic - U.S. Brands: Activella; Note: http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/500070.html

Progestins for Noncontraceptive Use •

Systemic - U.S. Brands: Amen; Aygestin; Crinone; Curretab; Cycrin; DepoProvera; Gesterol 50; Gesterol LA 250; Hy/Gestrone; Hylutin; Megace; Prodrox; Prometrium; Pro-Span; Provera http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202758.html

Commercial Databases In addition to the medications listed in the USP above, a number of commercial sites are available by subscription to physicians and their institutions. Or, you may be able to access these sources from your local medical library.

Mosby’s Drug Consult™ Mosby’s Drug Consult™ database (also available on CD-ROM and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Subscription information is available at the following hyperlink: http://www.mosbysdrugconsult.com/. PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html.

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Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee. If you have any questions about a medical treatment, the FDA may have an office near you. Look for their number in the blue pages of the phone book. You can also contact the FDA through its toll-free number, 1-888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.

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APPENDICES

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APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.

NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute9: •

Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm

•

National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/

•

National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html

•

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

•

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

•

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

•

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

•

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

9

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/

•

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.10 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:11 •

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

10

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). 11 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 Combined Health Information Database

A comprehensive source of information on clinical guidelines written for professionals is the Combined Health Information Database. You will need to limit your search to one of the following: Brochure/Pamphlet, Fact Sheet, or Information Package, and “hormone therapy” using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For the publication date, select “All Years.” Select your preferred language and the format option “Fact Sheet.” Type “hormone therapy” (or synonyms) into the “For these words:” box. The following is a sample result: •

Prostate Diseases: A Special Report from the Harvard Health Letter Source: Boston, MA: Harvard Health Letter. 1994. 25 p. Contact: Available from Harvard Medical School Health Publications Group. Department PRO, P.O. Box 380, Boston, MA 02117. (617) 432-1485. Fax (617) 432-1506. PRICE: $16 (as of 1995); multiple-copy discount rates available. Summary: This report provides information about prostatic diseases, focusing on benign prostatic hyperplasia (BPH) and prostate cancer. The first section of the report outlines the anatomy and physiology of the prostate and discusses diagnostic tests used to confirm prostatic diseases; tests covered include the digital rectal examination, the PSA test, ultrasonography, and biopsy. The second section discusses BPH, covering the symptoms of BPH, when to consult a health care provider, and treatment options including drug therapy, transurethral resection, laser surgery, balloon dilation, prostatic urethral stents, and heat therapies. The final section, on prostate cancer, discusses early detection strategies, more detailed diagnostic tests, the prevention of prostate cancer, and treatment options including watchful waiting, radical prostactectomy, radiation therapy, and hormone therapy. The booklet concludes with a brief discussion on the importance of support groups, a glossary of relevant terms, and a list of resource materials and organizations. 6 figures. 2 tables.

The NLM Gateway12 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.13 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. 12 13

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

The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH).

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Type “hormone therapy” (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 204261 1240 1152 186 17 206856

HSTAT14 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.15 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.16 Simply search by “hormone therapy” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

Coffee Break: Tutorials for Biologists17 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.18 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.19 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for

14

Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html.

15

The HSTAT URL is http://hstat.nlm.nih.gov/.

16

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. 17 Adapted from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html. 18 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. 19 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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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/.

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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 hormone therapy can appear at any moment and be published by a number of sources, the best approach to finding guidelines is to systematically scan the Internet-based services that post them.

Patient Guideline Sources The remainder of this chapter directs you to sources which either publish or can help you find additional guidelines on topics related to hormone therapy. 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 hormone therapy. 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 “hormone therapy”:

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•

Other guides Breast Cancer http://www.nlm.nih.gov/medlineplus/breastcancer.html Hormone Replacement Therapy http://www.nlm.nih.gov/medlineplus/hormonereplacementtherapy.html Hormones http://www.nlm.nih.gov/medlineplus/hormones.html Menopause http://www.nlm.nih.gov/medlineplus/menopause.html Pituitary Disorders http://www.nlm.nih.gov/medlineplus/pituitarydisorders.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 hormone therapy. 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: •

The most frequently asked questions when beginning growth hormone therapy Source: Oak Park, IL: MAGIC Foundation. n.d. 2 pp. Contact: Available from MAGIC Foundation for Children's Growth, 1327 North Harlem Avenue, Suite 701, Oak Park, IL 60302. Telephone: (708) 383- 0808 or (800) 3MAGIC3 / fax: (708) 383-0899 / e-mail: [email protected] / Web site: http://www.magicfoundation. Summary: This brochure contains a list of questions frequently asked by parents when their child begins growth hormone therapy. The questions are followed by brief answers. The National Guideline Clearinghouse™

The National Guideline Clearinghouse™ offers hundreds of evidence-based clinical practice guidelines published in the United States and other countries. You can search this site located at http://www.guideline.gov/ by using the keyword “hormone therapy” (or synonyms). The following was recently posted:

Patient Resources

•

175

Amended report from the NAMS Advisory Panel on postmenopausal hormone therapy Source: The North American Menopause Society - Private Nonprofit Organization; 2002 October 6; 7 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3464&nbr=2690&a mp;string=hormone+AND+therapy

•

Role of progestogen in hormone therapy for postmenopausal women: position statement of The North American Menopause Society Source: The North American Menopause Society - Private Nonprofit Organization; 2003 Mar-April; 20 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3736&nbr=2962&a mp;string=hormone+AND+therapy Healthfinder™

Healthfinder™ is sponsored by the U.S. Department of Health and Human Services and offers links to hundreds of other sites that contain healthcare information. This Web site is located at http://www.healthfinder.gov. Again, keyword searches can be used to find guidelines. The following was recently found in this database: •

Facts About Postmenopausal Hormone Therapy Summary: Choosing whether or not to use postmenopausal hormone therapy can be one of the most important health decisions women face as they age. Source: National Heart, Lung, and Blood Institute, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6793

•

Menopausal Hormone Therapy Information Summary: New findings from the Women's Health Initiative and other studies offer important information about the risks and benefits of long-term menopausal hormone therapy. Source: National Institutes of Health, U.S. Department of Health and Human Services http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=7589 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 hormone therapy. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html.

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Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •

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

•

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

•

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

•

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

•

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

•

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

•

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

Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to hormone therapy. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with hormone therapy. 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 hormone therapy. 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 “hormone therapy” (or a synonym), and you will receive information on all relevant organizations listed in the database. Health Hotlines directs you to toll-free numbers to over 300 organizations. You can access this database directly at http://www.sis.nlm.nih.gov/hotlines/. On this page, you are given

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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 “hormone therapy”. 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 “hormone therapy” (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 “hormone therapy” (or a synonym) into the search box, and click “Submit Query.”

179

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.20

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

20

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)21: •

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

•

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

•

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

•

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

•

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

•

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

•

California: Gateway Health Library (Sutter Gould Medical Foundation)

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

21

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

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•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

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•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

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•

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

•

New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

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•

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

•

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

•

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

•

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

185

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

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

•

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

•

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

•

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

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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).

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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HORMONE THERAPY DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Abdominal fat: Fat (adipose tissue) that is centrally distributed between the thorax and pelvis and that induces greater health risk. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] Ablation: The removal of an organ by surgery. [NIH] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Acidosis: A pathologic condition resulting from accumulation of acid or depletion of the alkaline reserve (bicarbonate content) in the blood and body tissues, and characterized by an increase in hydrogen ion concentration. [EU] Acne: A disorder of the skin marked by inflammation of oil glands and hair glands. [NIH] Acute lymphoblastic leukemia: ALL. A quickly progressing disease in which too many immature white blood cells called lymphoblasts are found in the blood and bone marrow. Also called acute lymphocytic leukemia. [NIH] Acute lymphocytic leukemia: ALL. A quickly progressing disease in which too many immature white blood cells called lymphoblasts are found in the blood and bone marrow. Also called acute lymphoblastic leukemia. [NIH] 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] Adenocarcinoma: A malignant epithelial tumor with a glandular organization. [NIH] Adenoma: A benign epithelial tumor with a glandular organization. [NIH] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adipocytes: Fat-storing cells found mostly in the abdominal cavity and subcutaneous tissue. Fat is usually stored in the form of tryglycerides. [NIH]

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Adipose Tissue: Connective tissue composed of fat cells lodged in the meshes of areolar tissue. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] Adjuvant Therapy: Treatment given after the primary treatment to increase the chances of a cure. Adjuvant therapy may include chemotherapy, radiation therapy, or hormone therapy. [NIH]

Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH] Adrenal Glands: Paired glands situated in the retroperitoneal tissues at the superior pole of each kidney. [NIH] Adrenal insufficiency: The reduced secretion of adrenal glands. [NIH] Adverse Effect: An unwanted side effect of treatment. [NIH] Aerobic: In biochemistry, reactions that need oxygen to happen or happen when oxygen is present. [NIH] Aerobic Exercise: A type of physical activity that includes walking, jogging, running, and dancing. Aerobic training improves the efficiency of the aerobic energy-producing systems that can improve cardiorespiratory endurance. [NIH] 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] Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Airway: A device for securing unobstructed passage of air into and out of the lungs during general anesthesia. [NIH] Alanine: A non-essential amino acid that occurs in high levels in its free state in plasma. It is produced from pyruvate by transamination. It is involved in sugar and acid metabolism, increases immunity, and provides energy for muscle tissue, brain, and the central nervous system. [NIH] Alendronate: A nonhormonal medication for the treatment of postmenopausal osteoporosis in women. This drug builds healthy bone, restoring some of the bone loss as a result of osteoporosis. [NIH] Alertness: A state of readiness to detect and respond to certain specified small changes

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occurring at random intervals in the environment. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alimentary: Pertaining to food or nutritive material, or to the organs of digestion. [EU] Alkaline: Having the reactions of an alkali. [EU] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Allogeneic: Taken from different individuals of the same species. [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] Alveolar Bone Loss: The resorption of bone in the supporting structures of the maxilla or mandible as a result of periodontal disease. [NIH] Amenorrhea: Absence of menstruation. [NIH] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. [NIH] Amnion: The extraembryonic membrane which contains the embryo and amniotic fluid. [NIH]

Amniotic Fluid: Amniotic cavity fluid which is produced by the amnion and fetal lungs and kidneys. [NIH] Amphetamines: Analogs or derivatives of amphetamine. Many are sympathomimetics and central nervous system stimulators causing excitation, vasopression, bronchodilation, and to varying degrees, anorexia, analepsis, nasal decongestion, and some smooth muscle relaxation. [NIH] Amplification: The production of additional copies of a chromosomal DNA sequence, found as either intrachromosomal or extrachromosomal DNA. [NIH] Anabolic: Relating to, characterized by, or promoting anabolism. [EU]

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Anaerobic: 1. Lacking molecular oxygen. 2. Growing, living, or occurring in the absence of molecular oxygen; pertaining to an anaerobe. [EU] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Anaphylatoxins: The family of peptides C3a, C4a, C5a, and C5a des-arginine produced in the serum during complement activation. They produce smooth muscle contraction, mast cell histamine release, affect platelet aggregation, and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from strongest to weakest is C5a, C3a, C4a, and C5a des-arginine. The latter is the so-called "classical" anaphylatoxin but shows no spasmogenic activity though it contains some chemotactic ability. [NIH] Anaplasia: Loss of structural differentiation and useful function of neoplastic cells. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Androgen suppression: Treatment to suppress or block the production of male hormones. Androgen suppression is achieved by surgical removal of the testicles, by taking female sex hormones, or by taking other drugs. Also called androgen ablation. [NIH] Androgen-Binding Protein: Carrier proteins produced in the Sertoli cells of the testis, secreted into the seminiferous tubules, and transported via the efferent ducts to the epididymis. They participate in the transport of androgens. Androgen-binding protein has the same amino acid sequence as sex hormone binding-globulin. They differ by their sites of synthesis and post-translational oligosacaccharide modifications. [NIH] Androgenic: Producing masculine characteristics. [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] Androstenedione: A steroid with androgenic properties that is produced in the testis, ovary, and adrenal cortex. It is a precursor to testosterone and other androgenic hormones. [NIH] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Angina: Chest pain that originates in the heart. [NIH] Angiogram: An x-ray of blood vessels; the person receives an injection of dye to outline the vessels on the x-ray. [NIH] Angioplasty: Endovascular reconstruction of an artery, which may include the removal of atheromatous plaque and/or the endothelial lining as well as simple dilatation. These are procedures performed by catheterization. When reconstruction of an artery is performed surgically, it is called endarterectomy. [NIH] 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

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new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anovulation: Suspension or cessation of ovulation in animals and humans. [NIH] Antagonism: Interference with, or inhibition of, the growth of a living organism by another living organism, due either to creation of unfavorable conditions (e. g. exhaustion of food supplies) or to production of a specific antibiotic substance (e. g. penicillin). [NIH] Antiandrogen therapy: Treatment with drugs used to block production or interfere with the action of male sex hormones. [NIH] Antiandrogens: Drugs used to block the production or interfere with the action of male sex hormones. [NIH] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]

Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Antibody therapy: Treatment with an antibody, a substance that can directly kill specific tumor cells or stimulate the immune system to kill tumor cells. [NIH] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Antidepressant: A drug used to treat depression. [NIH] Antidiabetic: An agent that prevents or alleviates diabetes. [EU] Antiepileptic: An agent that combats epilepsy. [EU] Antifungal: Destructive to fungi, or suppressing their reproduction or growth; effective against fungal infections. [EU] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. [NIH] Antihypertensive: An agent that reduces high blood pressure. [EU] Anti-infective: An agent that so acts. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH]

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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] Antiproliferative: Counteracting a process of proliferation. [EU] Antiseptic: A substance that inhibits the growth and development of microorganisms without necessarily killing them. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU] Anuria: Inability to form or excrete urine. [NIH] Anus: The opening of the rectum to the outside of the body. [NIH] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Aorta: The main trunk of the systemic arteries. [NIH] Apnea: A transient absence of spontaneous respiration. [NIH] Apolipoproteins: The protein components of lipoproteins which remain after the lipids to which the proteins are bound have been removed. They play an important role in lipid transport and metabolism. [NIH] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Applicability: A list of the commodities to which the candidate method can be applied as presented or with minor modifications. [NIH] Aqueous: Having to do with water. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Arsenic trioxide: An anticancer drug that induces programmed cell death (apoptosis) in certain cancer cells. [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] Articular: Of or pertaining to a joint. [EU] Ascites: Accumulation or retention of free fluid within the peritoneal cavity. [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] Astringent: Causing contraction, usually locally after topical application. [EU]

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Asymptomatic: Having no signs or symptoms of disease. [NIH] Atherogenic: Causing the formation of plaque in the lining of the arteries. [NIH] ATP: ATP an abbreviation for adenosine triphosphate, a compound which serves as a carrier of energy for cells. [NIH] Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] Attenuated: Strain with weakened or reduced virulence. [NIH] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Autoimmunity: Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by autoimmune diseases. [NIH] Autologous: Taken from an individual's own tissues, cells, or DNA. [NIH] Autonomic: Self-controlling; functionally independent. [EU] Axillary: Pertaining to the armpit area, including the lymph nodes that are located there. [NIH]

Axillary Artery: The continuation of the subclavian artery; it distributes over the upper limb, axilla, chest and shoulder. [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] Balloon Dilatation: Nonoperative repair of occluded vessels, ducts, or valves by insertion of a balloon catheter. It is used, amoung other things, to treat varices, torn retinas, renal and biliary calculi, gastric, bronchial and rectal stenoses, and heart valves, and includes catheterization with Fogarty and Foley catheters. [NIH] Balloon dilation: A treatment for benign prostatic hyperplasia or prostate enlargement. A tiny balloon is inflated inside the urethra to make it wider so urine can flow more freely from the bladder. [NIH] Barbiturate: A drug with sedative and hypnotic effects. Barbiturates have been used as sedatives and anesthetics, and they have been used to treat the convulsions associated with epilepsy. [NIH] Baroreflex: A negative feedback system which buffers short-term changes in blood pressure. Increased pressure stretches blood vessels which activates pressoreceptors (baroreceptors) in the vessel walls. The net response of the central nervous system is a reduction of central sympathetic outflow. This reduces blood pressure both by decreasing peripheral vascular resistance and by lowering cardiac output. Because the baroreceptors are tonically active, the baroreflex can compensate rapidly for both increases and decreases in blood pressure. [NIH]

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] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]

Benign prostatic hyperplasia: A benign (noncancerous) condition in which an overgrowth

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of prostate tissue pushes against the urethra and the bladder, blocking the flow of urine. Also called benign prostatic hypertrophy or BPH. [NIH] Benign tumor: A noncancerous growth that does not invade nearby tissue or spread to other parts of the body. [NIH] Beta-Thalassemia: A disorder characterized by reduced synthesis of the beta chains of hemoglobin. There is retardation of hemoglobin A synthesis in the heterozygous form (thalassemia minor), which is asymptomatic, while in the homozygous form (thalassemia major, Cooley's anemia, Mediterranean anemia, erythroblastic anemia), which can result in severe complications and even death, hemoglobin A synthesis is absent. [NIH] Bewilderment: Impairment or loss of will power. [NIH] Bicalutamide: An anticancer drug that belongs to the family of drugs called antiandrogens. [NIH]

Bilateral: Affecting both the right and left side of body. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Biliary: Having to do with the liver, bile ducts, and/or gallbladder. [NIH] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] Bioavailable: The ability of a drug or other substance to be absorbed and used by the body. Orally bioavailable means that a drug or other substance that is taken by mouth can be absorbed and used by the body. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biological therapy: Treatment to stimulate or restore the ability of the immune system to fight infection and disease. Also used to lessen side effects that may be caused by some cancer treatments. Also known as immunotherapy, biotherapy, or biological response modifier (BRM) therapy. [NIH] Biomarkers: Substances sometimes found in an increased amount in the blood, other body fluids, or tissues and that may suggest the presence of some types of cancer. Biomarkers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and GI tract cancers), and PSA (prostate cancer). Also called tumor markers. [NIH] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Biotransformation: The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alteration may be either nonsynthetic (oxidation-reduction, hydrolysis) or synthetic (glucuronide formation, sulfate conjugation, acetylation, methylation). This also includes metabolic detoxication and

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clearance. [NIH] Bladder: The organ that stores urine. [NIH] Blast phase: The phase of chronic myelogenous leukemia in which the number of immature, abnormal white blood cells in the bone marrow and blood is extremely high. Also called blast crisis. [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 Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blot: To transfer DNA, RNA, or proteins to an immobilizing matrix such as nitrocellulose. [NIH]

Body Composition: The relative amounts of various components in the body, such as percent body fat. [NIH] Body Fluids: Liquid components of living organisms. [NIH] Body Mass Index: One of the anthropometric measures of body mass; it has the highest correlation with skinfold thickness or body density. [NIH] Bone Density: The amount of mineral per square centimeter of bone. This is the definition used in clinical practice. Actual bone density would be expressed in grams per milliliter. It is most frequently measured by photon absorptiometry or x-ray computed tomography. [NIH] Bone Development: Gross development of bones from fetus to adult. It includes osteogenesis, which is restricted to formation and development of bone from the undifferentiated cells of the germ layers of the embryo. It does not include osseointegration. [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 Resorption: Bone loss due to osteoclastic activity. [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] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] Brachial: All the nerves from the arm are ripped from the spinal cord. [NIH]

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Brachial Artery: The continuation of the axillary artery; it branches into the radial and ulnar arteries. [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] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]

Breakdown: A physical, metal, or nervous collapse. [NIH] Bromine: A halogen with the atomic symbol Br, atomic number 36, and atomic weight 79.904. It is a volatile reddish-brown liquid that gives off suffocating vapors, is corrosive to the skin, and may cause severe gastroenteritis if ingested. [NIH] Bronchial: Pertaining to one or more bronchi. [EU] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Buffers: A chemical system that functions to control the levels of specific ions in solution. When the level of hydrogen ion in solution is controlled the system is called a pH buffer. [NIH]

Buserelin: A potent and durable analog of naturally occurring gonadotropin-releasing hormone (GnRH). [NIH] Bypass: A surgical procedure in which the doctor creates a new pathway for the flow of body fluids. [NIH] Caffeine: A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine's most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. It also relaxes smooth muscle, stimulates cardiac muscle, stimulates diuresis, and appears to be useful in the treatment of some types of headache. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide phosphodiesterases, antagonism of adenosine receptors, and modulation of intracellular calcium handling. [NIH] Calcifediol: The major circulating metabolite of vitamin D3 produced in the liver and the best indicator of the body's vitamin D stores. It is effective in the treatment of rickets and osteomalacia, both in azotemic and non-azotemic patients. Calcifediol also has mineralizing properties. [NIH] Calcitriol: The physiologically active form of vitamin D. It is formed primarily in the kidney by enzymatic hydroxylation of 25-hydroxycholecalciferol (calcifediol). Its production is stimulated by low blood calcium levels and parathyroid hormone. Calcitriol increases intestinal absorption of calcium and phosphorus, and in concert with parathyroid hormone increases bone resorption. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in

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many enzymatic processes. [NIH] Calculi: An abnormal concretion occurring mostly in the urinary and biliary tracts, usually composed of mineral salts. Also called stones. [NIH] Caloric intake: Refers to the number of calories (energy content) consumed. [NIH] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [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] Carboplatin: An organoplatinum compound that possesses antineoplastic activity. [NIH] Carcinogen: Any substance that causes cancer. [NIH] Carcinogenesis: The process by which normal cells are transformed into cancer cells. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]

Cardiac: Having to do with the heart. [NIH] Cardiac Output: The volume of blood passing through the heart per unit of time. It is usually expressed as liters (volume) per minute so as not to be confused with stroke volume (volume per beat). [NIH] Cardiology: The study of the heart, its physiology, and its functions. [NIH] Cardiomyopathy: A general diagnostic term designating primary myocardial disease, often of obscure or unknown etiology. [EU] Cardiorespiratory: Relating to the heart and lungs and their function. [EU] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] Cardiovascular System: The heart and the blood vessels by which blood is pumped and circulated through the body. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Case series: A group or series of case reports involving patients who were given similar treatment. Reports of case series usually contain detailed information about the individual patients. This includes demographic information (for example, age, gender, ethnic origin) and information on diagnosis, treatment, response to treatment, and follow-up after treatment. [NIH] Catabolism: Any destructive metabolic process by which organisms convert substances into excreted compounds. [EU] Catechol: A chemical originally isolated from a type of mimosa tree. Catechol is used as an astringent, an antiseptic, and in photography, electroplating, and making other chemicals. It

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can also be man-made. [NIH] Catheterization: Use or insertion of a tubular device into a duct, blood vessel, hollow organ, or body cavity for injecting or withdrawing fluids for diagnostic or therapeutic purposes. It differs from intubation in that the tube here is used to restore or maintain patency in obstructions. [NIH] Catheters: A small, flexible tube that may be inserted into various parts of the body to inject or remove liquids. [NIH] Caudal: Denoting a position more toward the cauda, or tail, than some specified point of reference; same as inferior, in human anatomy. [EU] Causal: Pertaining to a cause; directed against a cause. [EU] Cause of Death: Factors which produce cessation of all vital bodily functions. They can be analyzed from an epidemiologic viewpoint. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] 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 Cycle Proteins: Proteins that control the cell division cycle. This family of proteins includes a wide variety of classes, including cyclin-dependent kinases, mitogen-activated kinases, cyclins, and phosphoprotein phosphatases (phosphoprotein phosphatase) as well as their putative substrates such as chromatin-associated proteins, cytoskeletal proteins, and transcription factors. [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 proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Respiration: The metabolic process of all living cells (animal and plant) in which oxygen is used to provide a source of energy for the cell. [NIH] Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. [NIH] Cell Transplantation: Transference of cells within an individual, between individuals of the same species, or between individuals of different species. [NIH] Cellobiose: A disaccharide consisting of two glucose units in beta (1-4) glycosidic linkage. Obtained from the partial hydrolysis of cellulose. [NIH] Cellulose: A polysaccharide with glucose units linked as in cellobiose. It is the chief constituent of plant fibers, cotton being the purest natural form of the substance. As a raw material, it forms the basis for many derivatives used in chromatography, ion exchange materials, explosives manufacturing, and pharmaceutical preparations. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Central Nervous System Infections: Pathogenic infections of the brain, spinal cord, and

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meninges. DNA virus infections; RNA virus infections; bacterial infections; mycoplasma infections; Spirochaetales infections; fungal infections; protozoan infections; helminthiasis; and prion diseases may involve the central nervous system as a primary or secondary process. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Cervical: Relating to the neck, or to the neck of any organ or structure. Cervical lymph nodes are located in the neck; cervical cancer refers to cancer of the uterine cervix, which is the lower, narrow end (the "neck") of the uterus. [NIH] Cervical Ripening: A change in the cervix with respect to its readiness to relax. The cervix becomes softer, more flexible, more distensible, and shorter in the final weeks of pregnancy. Though naturally occurring during normal pregnancy, it can also be induced for certain cases of prolonged or high-risk pregnancy by administration of hormones. [NIH] Cervix: The lower, narrow end of the uterus that forms a canal between the uterus and vagina. [NIH] Character: In current usage, approximately equivalent to personality. The sum of the relatively fixed personality traits and habitual modes of response of an individual. [NIH] Chemotactic Factors: Chemical substances that attract or repel cells or organisms. The concept denotes especially those factors released as a result of tissue injury, invasion, or immunologic activity, that attract leukocytes, macrophages, or other cells to the site of infection or insult. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] Chlormadinone Acetate: An orally active synthetic progestational hormone used often in combinations as an oral contraceptive. [NIH] Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Cholesterol Esters: Fatty acid esters of cholesterol which constitute about two-thirds of the cholesterol in the plasma. The accumulation of cholesterol esters in the arterial intima is a characteristic feature of atherosclerosis. [NIH] Cholinergic: Resembling acetylcholine in pharmacological action; stimulated by or releasing acetylcholine or a related compound. [EU] Chromaffin System: The cells of the body which stain with chromium salts. They occur along the sympathetic nerves, in the adrenal gland, and in various other organs. [NIH] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic Disease: Disease or ailment of long duration. [NIH] Chronic lymphocytic leukemia: A slowly progressing disease in which too many white blood cells (called lymphocytes) are found in the body. [NIH]

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Chronic myelogenous leukemia: CML. A slowly progressing disease in which too many white blood cells are made in the bone marrow. Also called chronic myeloid leukemia or chronic granulocytic leukemia. [NIH] Chronic phase: Refers to the early stages of chronic myelogenous leukemia or chronic lymphocytic leukemia. The number of mature and immature abnormal white blood cells in the bone marrow and blood is higher than normal, but lower than in the accelerated or blast phase. [NIH] Chronic renal: Slow and progressive loss of kidney function over several years, often resulting in end-stage renal disease. People with end-stage renal disease need dialysis or transplantation to replace the work of the kidneys. [NIH] Chylomicrons: A class of lipoproteins that carry dietary cholesterol and triglycerides from the small intestines to the tissues. [NIH] Circadian: Repeated more or less daily, i. e. on a 23- to 25-hour cycle. [NIH] Circulatory system: The system that contains the heart and the blood vessels and moves blood throughout the body. This system helps tissues get enough oxygen and nutrients, and it helps them get rid of waste products. The lymph system, which connects with the blood system, is often considered part of the circulatory system. [NIH] CIS: Cancer Information Service. The CIS is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER, or by using the Web site at http://cis.nci.nih.gov. [NIH] Cisplatin: An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle. [NIH] Clamp: A u-shaped steel rod used with a pin or wire for skeletal traction in the treatment of certain fractures. [NIH] Clear cell carcinoma: A rare type of tumor of the female genital tract in which the inside of the cells looks clear when viewed under a microscope. [NIH] Climacteric: Physiologic period, characterized by endocrine, somatic, and psychic changes with the termination of ovarian function in the female. It may also accompany the normal diminution of sexual activity in the male. [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] Clomiphene: A stilbene derivative that functions both as a partial estrogen agonist and complete estrogen antagonist depending on the target tissue. It antagonizes the estrogen receptor thereby initiating or augmenting ovulation in anovulatory women. [NIH] Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Coagulation: 1. The process of clot formation. 2. In colloid chemistry, the solidification of a sol into a gelatinous mass; an alteration of a disperse phase or of a dissolved solid which causes the separation of the system into a liquid phase and an insoluble mass called the clot

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or curd. Coagulation is usually irreversible. 3. In surgery, the disruption of tissue by physical means to form an amorphous residuum, as in electrocoagulation and photocoagulation. [EU] Coca: Any of several South American shrubs of the Erythroxylon genus (and family) that yield cocaine; the leaves are chewed with alum for CNS stimulation. [NIH] Cocaine: An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. [NIH] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Cognition: Intellectual or mental process whereby an organism becomes aware of or obtains knowledge. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Collagen disease: A term previously used to describe chronic diseases of the connective tissue (e.g., rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis), but now is thought to be more appropriate for diseases associated with defects in collagen, which is a component of the connective tissue. [NIH] Collapse: 1. A state of extreme prostration and depression, with failure of circulation. 2. Abnormal falling in of the walls of any part of organ. [EU] Colorectal: Having to do with the colon or the rectum. [NIH] Colorectal Cancer: Cancer that occurs in the colon (large intestine) or the rectum (the end of the large intestine). A number of digestive diseases may increase a person's risk of colorectal cancer, including polyposis and Zollinger-Ellison Syndrome. [NIH] Combination chemotherapy: Treatment using more than one anticancer drug. [NIH] Combination Therapy: Association of 3 drugs to treat AIDS (AZT + DDC or DDI + protease inhibitor). [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1

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to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complete remission: The disappearance of all signs of cancer. Also called a complete response. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Computed tomography: CT scan. A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized tomography and computerized axial tomography (CAT) scan. [NIH] Computerized axial tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called CAT scan, computed tomography (CT scan), or computerized tomography. [NIH] Computerized tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized axial tomography (CAT) scan and computed tomography (CT scan). [NIH] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU] Concomitant: Accompanying; accessory; joined with another. [EU] Condoms: A sheath that is worn over the penis during sexual behavior in order to prevent pregnancy or spread of sexually transmitted disease. [NIH] Confounding: Extraneous variables resulting in outcome effects that obscure or exaggerate the "true" effect of an intervention. [NIH] Confusion: A mental state characterized by bewilderment, emotional disturbance, lack of clear thinking, and perceptual disorientation. [NIH]

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Conjugated: Acting or operating as if joined; simultaneous. [EU] Conjugation: 1. The act of joining together or the state of being conjugated. 2. A sexual process seen in bacteria, ciliate protozoa, and certain fungi in which nuclear material is exchanged during the temporary fusion of two cells (conjugants). In bacterial genetics a form of sexual reproduction in which a donor bacterium (male) contributes some, or all, of its DNA (in the form of a replicated set) to a recipient (female) which then incorporates differing genetic information into its own chromosome by recombination and passes the recombined set on to its progeny by replication. In ciliate protozoa, two conjugants of separate mating types exchange micronuclear material and then separate, each now being a fertilized cell. In certain fungi, the process involves fusion of two gametes, resulting in union of their nuclei and formation of a zygote. 3. In chemistry, the joining together of two compounds to produce another compound, such as the combination of a toxic product with some substance in the body to form a detoxified product, which is then eliminated. [EU] 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] Consciousness: Sense of awareness of self and of the environment. [NIH] Constriction: The act of constricting. [NIH] Consumption: Pulmonary tuberculosis. [NIH] Continuum: An area over which the vegetation or animal population is of constantly changing composition so that homogeneous, separate communities cannot be distinguished. [NIH]

Contraception: Use of agents, devices, methods, or procedures which diminish the likelihood of or prevent conception. [NIH] Contraceptive: An agent that diminishes the likelihood of or prevents conception. [EU] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Control group: In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works. [NIH] 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]

Contusions: Injuries resulting in hemorrhage, usually manifested in the skin. [NIH] Conventional therapy: A currently accepted and widely used treatment for a certain type of disease, based on the results of past research. Also called conventional treatment. [NIH] Conventional treatment: A currently accepted and widely used treatment for a certain type of disease, based on the results of past research. Also called conventional therapy. [NIH] 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] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments,

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etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary Artery Bypass: Surgical therapy of ischemic coronary artery disease achieved by grafting a section of saphenous vein, internal mammary artery, or other substitute between the aorta and the obstructed coronary artery distal to the obstructive lesion. [NIH] Coronary Circulation: The circulation of blood through the coronary vessels of the heart. [NIH]

Coronary Disease: Disorder of cardiac function due to an imbalance between myocardial function and the capacity of the coronary vessels to supply sufficient flow for normal function. It is a form of myocardial ischemia (insufficient blood supply to the heart muscle) caused by a decreased capacity of the coronary vessels. [NIH] Coronary heart disease: A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Coronary Vessels: The veins and arteries of the heart. [NIH] Corpus: The body of the uterus. [NIH] Corpus Luteum: The yellow glandular mass formed in the ovary by an ovarian follicle that has ruptured and discharged its ovum. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Corticosteroid: Any of the steroids elaborated by the adrenal cortex (excluding the sex hormones of adrenal origin) in response to the release of corticotrophin (adrenocorticotropic hormone) by the pituitary gland, to any of the synthetic equivalents of these steroids, or to angiotensin II. They are divided, according to their predominant biological activity, into three major groups: glucocorticoids, chiefly influencing carbohydrate, fat, and protein metabolism; mineralocorticoids, affecting the regulation of electrolyte and water balance; and C19 androgens. Some corticosteroids exhibit both types of activity in varying degrees, and others exert only one type of effect. The corticosteroids are used clinically for hormonal replacement therapy, for suppression of ACTH secretion by the anterior pituitary, as antineoplastic, antiallergic, and anti-inflammatory agents, and to suppress the immune response. Called also adrenocortical hormone and corticoid. [EU] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to stress. [NIH] Cortisone: A natural steroid hormone produced in the adrenal gland. It can also be made in the laboratory. Cortisone reduces swelling and can suppress immune responses. [NIH] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Craniocerebral Trauma: Traumatic injuries involving the cranium and intracranial structures (i.e., brain; cranial nerves; meninges; and other structures). Injuries may be classified by whether or not the skull is penetrated (i.e., penetrating vs. nonpenetrating) or whether there is an associated hemorrhage. [NIH] Creatine: An amino acid that occurs in vertebrate tissues and in urine. In muscle tissue,

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creatine generally occurs as phosphocreatine. Creatine is excreted as creatinine in the urine. [NIH]

Creatinine: A compound that is excreted from the body in urine. Creatinine levels are measured to monitor kidney function. [NIH] Crossing-over: The exchange of corresponding segments between chromatids of homologous chromosomes during meiosia, forming a chiasma. [NIH] Cryptorchidism: A condition in which one or both testicles fail to move from the abdomen, where they develop before birth, into the scrotum. Cryptorchidism may increase the risk for development of testicular cancer. Also called undescended testicles. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Having to do with the skin. [NIH] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] Cyclin: Molecule that regulates the cell cycle. [NIH] Cyclin-Dependent Kinases: Protein kinases that control cell cycle progression in all eukaryotes and require physical association with cyclins to achieve full enzymatic activity. Cyclin-dependent kinases are regulated by phosphorylation and dephosphorylation events. [NIH]

Cyclophosphamide: Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the liver to form the active aldophosphamide. It is used in the treatment of lymphomas, leukemias, etc. Its side effect, alopecia, has been made use of in defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer. [NIH] 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] Cyproterone: An anti-androgen that, in the form of its acetate, also has progestational properties. It is used in the treatment of hypersexuality in males, as a palliative in prostatic carcinoma, and, in combination with estrogen, for the therapy of severe acne and hirsutism in females. [NIH] Cyst: A sac or capsule filled with fluid. [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] Cytomegalovirus: A genus of the family Herpesviridae, subfamily Betaherpesvirinae, infecting the salivary glands, liver, spleen, lungs, eyes, and other organs, in which they produce characteristically enlarged cells with intranuclear inclusions. Infection with

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Cytomegalovirus is also seen as an opportunistic infection in AIDS. [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] Cytoskeletal Proteins: Major constituent of the cytoskeleton found in the cytoplasm of eukaryotic cells. They form a flexible framework for the cell, provide attachment points for organelles and formed bodies, and make communication between parts of the cell possible. [NIH]

Cytotoxic: Cell-killing. [NIH] Cytotoxicity: Quality of being capable of producing a specific toxic action upon cells of special organs. [NIH] Data Collection: Systematic gathering of data for a particular purpose from various sources, including questionnaires, interviews, observation, existing records, and electronic devices. The process is usually preliminary to statistical analysis of the data. [NIH] Databases, Bibliographic: Extensive collections, reputedly complete, of references and citations to books, articles, publications, etc., generally on a single subject or specialized subject area. Databases can operate through automated files, libraries, or computer disks. The concept should be differentiated from factual databases which is used for collections of data and facts apart from bibliographic references to them. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Dehydroepiandrosterone: DHEA. A substance that is being studied as a cancer prevention drug. It belongs to the family of drugs called steroids. [NIH] Deja Vu: A subjective feeling that an experience which is occurring for the first time has been experienced before. [NIH] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Dementia: An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Dental Care: The total of dental diagnostic, preventive, and restorative services provided to meet the needs of a patient (from Illustrated Dictionary of Dentistry, 1982). [NIH] Dental Caries: Localized destruction of the tooth surface initiated by decalcification of the enamel followed by enzymatic lysis of organic structures and leading to cavity formation. If left unchecked, the cavity may penetrate the enamel and dentin and reach the pulp. The three most prominent theories used to explain the etiology of the disase are that acids produced by bacteria lead to decalcification; that micro-organisms destroy the enamel protein; or that keratolytic micro-organisms produce chelates that lead to decalcification. [NIH]

Deoxyribonucleic: A polymer of subunits called deoxyribonucleotides which is the primary genetic material of a cell, the material equivalent to genetic information. [NIH] Deoxyribonucleic acid: A polymer of subunits called deoxyribonucleotides which is the

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primary genetic material of a cell, the material equivalent to genetic information. [NIH] Deprivation: Loss or absence of parts, organs, powers, or things that are needed. [EU] DES: Diethylstilbestrol. A synthetic hormone that was prescribed from the early 1940s until 1971 to help women with complications of pregnancy. DES has been linked to an increased risk of clear cell carcinoma of the vagina in daughters of women who used DES. DES may also increase the risk of breast cancer in women who used DES. [NIH] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [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 Imaging: Any visual display of structural or functional patterns of organs or tissues for diagnostic evaluation. It includes measuring physiologic and metabolic responses to physical and chemical stimuli, as well as ultramicroscopy. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Dialyzer: A part of the hemodialysis machine. (See hemodialysis under dialysis.) The dialyzer has two sections separated by a membrane. One section holds dialysate. The other holds the patient's blood. [NIH] Diastolic: Of or pertaining to the diastole. [EU] Diencephalon: The paired caudal parts of the prosencephalon from which the thalamus, hypothalamus, epithalamus, and subthalamus are derived. [NIH] Diffusion: The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space; a major mechanism of biological transport. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive system: The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] Digestive tract: The organs through which food passes when food is eaten. These organs are the mouth, esophagus, stomach, small and large intestines, and rectum. [NIH] Digital rectal examination: DRE. An examination in which a doctor inserts a lubricated, gloved finger into the rectum to feel for abnormalities. [NIH] Dihydrotestosterone: Anabolic agent. [NIH] Dilatation: The act of dilating. [NIH] Dilated cardiomyopathy: Heart muscle disease that leads to enlargement of the heart's chambers, robbing the heart of its pumping ability. [NIH] Dilation: A process by which the pupil is temporarily enlarged with special eye drops (mydriatic); allows the eye care specialist to better view the inside of the eye. [NIH] Dilution: A diluted or attenuated medicine; in homeopathy, the diffusion of a given quantity of a medicinal agent in ten or one hundred times the same quantity of water. [NIH] Diphenylamine: In humans it may be irritating to mucous membranes. Methemoglobinemia has been produced experimentally. In veterinary use, it is one of active

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ingredients in topical agents for prevention and treatment of screwworm infestation. An indicator in tests for nitrate poisoning. [NIH] Diploid: Having two sets of chromosomes. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] 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] Disease-specific survival: The percentage of subjects in a study who have survived a particular disease for a defined period of time. Usually reported as time since diagnosis or treatment. In calculating this percentage, only deaths from the disease being studied are counted. Subjects who died from some other cause are not included in the calculation. [NIH] Disorientation: The loss of proper bearings, or a state of mental confusion as to time, place, or identity. [EU] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Diuresis: Increased excretion of urine. [EU] DNA Topoisomerase: An enzyme catalyzing ATP-independent breakage of single-stranded DNA, followed by passage and rejoining of another single-stranded DNA. This enzyme class brings about the conversion of one topological isomer of DNA into another, e.g., the relaxation of superhelical turns in DNA, the interconversion of simple and knotted rings of single-stranded DNA, and the intertwisting of single-stranded rings of complementary sequences. (From Enzyme Nomenclature, 1992) EC 5.99.1.2. [NIH] Docetaxel: An anticancer drug that belongs to the family of drugs called mitotic inhibitors. [NIH]

Domestic Violence: Deliberate, often repetitive, physical abuse by one family member against another: marital partners, parents, children, siblings, or any other member of a household. [NIH] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] Dosage Forms: Completed forms of the pharmaceutical preparation in which prescribed doses of medication are included. They are designed to resist action by gastric fluids, prevent vomiting and nausea, reduce or alleviate the undesirable taste and smells associated with oral administration, achieve a high concentration of drug at target site, or produce a

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delayed or long-acting drug effect. They include capsules, liniments, ointments, pharmaceutical solutions, powders, tablets, etc. [NIH] Dose-dependent: Refers to the effects of treatment with a drug. If the effects change when the dose of the drug is changed, the effects are said to be dose dependent. [NIH] Double-blinded: A clinical trial in which neither the medical staff nor the person knows which of several possible therapies the person is receiving. [NIH] Drive: A state of internal activity of an organism that is a necessary condition before a given stimulus will elicit a class of responses; e.g., a certain level of hunger (drive) must be present before food will elicit an eating response. [NIH] Drug 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] Duct: A tube through which body fluids pass. [NIH] Duodenum: The first part of the small intestine. [NIH] Dwarfism: The condition of being undersized as a result of premature arrest of skeletal growth. It may be caused by insufficient secretion of growth hormone (pituitary dwarfism). [NIH]

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] Dyspareunia: Painful sexual intercourse. [NIH] Dysplasia: Cells that look abnormal under a microscope but are not cancer. [NIH] Dystrophic: Pertaining to toxic habitats low in nutrients. [NIH] Eating Disorders: A group of disorders characterized by physiological and psychological disturbances in appetite or food intake. [NIH] Eccentricity: Oddness of behavior or conduct without insanity. [NIH] Echocardiography: Ultrasonic recording of the size, motion, and composition of the heart and surrounding tissues. The standard approach is transthoracic. [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

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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] Elastin: The protein that gives flexibility to tissues. [NIH] Electrocardiogram: Measurement of electrical activity during heartbeats. [NIH] Electrocoagulation: Electrosurgical procedures used to treat hemorrhage (e.g., bleeding ulcers) and to ablate tumors, mucosal lesions, and refractory arrhythmias. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] Electrophysiological: Pertaining to electrophysiology, that is a branch of physiology that is concerned with the electric phenomena associated with living bodies and involved in their functional activity. [EU] Electroplating: Coating with a metal or alloy by electrolysis. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Embryo Transfer: Removal of a mammalian embryo from one environment and replacement in the same or a new environment. The embryo is usually in the pre-nidation phase, i.e., a blastocyst. The process includes embryo or blastocyst transplantation or transfer after in vitro fertilization and transfer of the inner cell mass of the blastocyst. It is not used for transfer of differentiated embryonic tissue, e.g., germ layer cells. [NIH] Embryology: The study of the development of an organism during the embryonic and fetal stages of life. [NIH] Emulsion: A preparation of one liquid distributed in small globules throughout the body of a second liquid. The dispersed liquid is the discontinuous phase, and the dispersion medium is the continuous phase. When oil is the dispersed liquid and an aqueous solution is the continuous phase, it is known as an oil-in-water emulsion, whereas when water or aqueous solution is the dispersed phase and oil or oleaginous substance is the continuous phase, it is known as a water-in-oil emulsion. Pharmaceutical emulsions for which official standards have been promulgated include cod liver oil emulsion, cod liver oil emulsion with malt, liquid petrolatum emulsion, and phenolphthalein in liquid petrolatum emulsion. [EU] Enanthate: An oily injectable contraceptive given every 8 weeks. [NIH] Endarterectomy: Surgical excision, performed under general anesthesia, of the atheromatous tunica intima of an artery. When reconstruction of an artery is performed as an endovascular procedure through a catheter, it is called atherectomy. [NIH] Endemic: Present or usually prevalent in a population or geographical area at all times; said of a disease or agent. Called also endemial. [EU] Endocrine Glands: Ductless glands that secrete substances which are released directly into the circulation and which influence metabolism and other body functions. [NIH] Endocrine System: The system of glands that release their secretions (hormones) directly into the circulatory system. In addition to the endocrine glands, included are the chromaffin

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system and the neurosecretory systems. [NIH] Endocrinology: A subspecialty of internal medicine concerned with the metabolism, physiology, and disorders of the endocrine system. [NIH] Endometrial: Having to do with the endometrium (the layer of tissue that lines the uterus). [NIH]

Endometriosis: A condition in which tissue more or less perfectly resembling the uterine mucous membrane (the endometrium) and containing typical endometrial granular and stromal elements occurs aberrantly in various locations in the pelvic cavity. [NIH] Endometrium: The layer of tissue that lines the uterus. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium, Lymphatic: Unbroken cellular lining (intima) of the lymph vessels (e.g., the high endothelial lymphatic venules). It is more permeable than vascular endothelium, lacking selective absorption and functioning mainly to remove plasma proteins that have filtered through the capillaries into the tissue spaces. [NIH] Endothelium, Vascular: Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components from interstitium to lumen; this function has been most intensively studied in the blood capillaries. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] Endotoxic: Of, relating to, or acting as an endotoxin (= a heat-stable toxin, associated with the outer membranes of certain gram-negative bacteria. Endotoxins are not secreted and are released only when the cells are disrupted). [EU] 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] Enhancer: Transcriptional element in the virus genome. [NIH] Enteral Nutrition: Nutritional support given via the alimentary canal or any route connected to the gastrointestinal system (i.e., the enteral route). This includes oral feeding, sip feeding, and tube feeding using nasogastric, gastrostomy, and jejunostomy tubes. [NIH] 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]

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Epidemiological: Relating to, or involving epidemiology. [EU] 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] Epithelial ovarian cancer: Cancer that occurs in the cells lining the ovaries. [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] Equilenin: 3-Hydroxyestra-1,3,5(10),6,8-pentaen-17-one. A naturally occurring steroid with estrogenic activity obtained from the urine of pregnant mares. [NIH] Equilin: 3-Hydroxyestra-1,3,5(10)7-tetraen-17-one. A naturally occurring steroid with estrogenic activity obtained from the urine of pregnant mares. [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]

Estradiol: The most potent mammalian estrogenic hormone. It is produced in the ovary, placenta, testis, and possibly the adrenal cortex. [NIH] Estramustine: A nitrogen mustard linked to estradiol, usually as phosphate; used to treat prostatic neoplasms; also has radiation protective properties. [NIH] Estrogen: One of the two female sex hormones. [NIH] Estrogen Antagonists: Compounds which inhibit or antagonize the action or biosynthesis of estrogen. [NIH] Estrogen receptor: ER. Protein found on some cancer cells to which estrogen will attach. [NIH]

Estrogen receptor positive: ER+. Breast cancer cells that have a protein (receptor molecule) to which estrogen will attach. Breast cancer cells that are ER+ need the hormone estrogen to grow and will usually respond to hormone (antiestrogen) therapy that blocks these receptor sites. [NIH] Estrogen Replacement Therapy: The use of hormonal agents with estrogen-like activity in postmenopausal or other estrogen-deficient women to alleviate effects of hormone deficiency, such as vasomotor symptoms, dyspareunia, and progressive development of osteoporosis. This may also include the use of progestational agents in combination therapy. [NIH]

Estrone: 3-Hydroxyestra-1,3,5(10)-trien-17-one. A metabolite of estradiol but possessing less biological activity. It is found in the urine of pregnant women and mares, in the human placenta, and in the urine of bulls and stallions. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), estrone may reasonably be anticipated to be a carcinogen (Merck, 11th ed). [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] Excipient: Any more or less inert substance added to a prescription in order to confer a suitable consistency or form to the drug; a vehicle. [EU] 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]

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Excitatory: When cortical neurons are excited, their output increases and each new input they receive while they are still excited raises their output markedly. [NIH] Excitatory Amino Acids: Endogenous amino acids released by neurons as excitatory neurotransmitters. Glutamic acid is the most common excitatory neurotransmitter in the brain. Aspartic acid has been regarded as an excitatory transmitter for many years, but the extent of its role as a transmitter is unclear. [NIH] Excrete: To get rid of waste from the body. [NIH] Exercise Test: Controlled physical activity, more strenuous than at rest, which is performed in order to allow assessment of physiological functions, particularly cardiovascular and pulmonary, but also aerobic capacity. Maximal (most intense) exercise is usually required but submaximal exercise is also used. The intensity of exercise is often graded, using criteria such as rate of work done, oxygen consumption, and heart rate. Physiological data obtained from an exercise test may be used for diagnosis, prognosis, and evaluation of disease severity, and to evaluate therapy. Data may also be used in prescribing exercise by determining a person's exercise capacity. [NIH] Exhaustion: The feeling of weariness of mind and body. [NIH] Exisulind: A drug that is being studied in the treatment and prevention of cancer. It has been shown to cause apoptosis (cell death) in cancerous and precancerous cells by acting through a group of cellular enzymes called cGMP phosphodiesterases. [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] External radiation: Radiation therapy that uses a machine to aim high-energy rays at the cancer. Also called external-beam radiation. [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] Extreme obesity: A body mass index [NIH] Exudate: Material, such as fluid, cells, or cellular debris, which has escaped from blood vessels and has been deposited in tissues or on tissue surfaces, usually as a result of inflammation. An exudate, in contrast to a transudate, is characterized by a high content of protein, cells, or solid materials derived from cells. [EU] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]

Femoral: Pertaining to the femur, or to the thigh. [EU] Femur: The longest and largest bone of the skeleton, it is situated between the hip and the knee. [NIH] Fertilization in Vitro: Fertilization of an egg outside the body when the egg is normally

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fertilized in the body. [NIH] Fetal Development: Morphologic and physiologic growth and development of the mammalian embryo or fetus. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibrin: A protein derived from fibrinogen in the presence of thrombin, which forms part of the blood clot. [NIH] Fibrinogen: Plasma glycoprotein clotted by thrombin, composed of a dimer of three nonidentical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products. [NIH] Fibrinolysis: The natural enzymatic dissolution of fibrin. [NIH] Fibrinolytic: Pertaining to, characterized by, or causing the dissolution of fibrin by enzymatic action [EU] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibroid: A benign smooth muscle tumor, usually in the uterus or gastrointestinal tract. Also called leiomyoma. [NIH] Finasteride: An orally active testosterone 5-alpha-reductase inhibitor. It is used as a surgical alternative for treatment of benign prostatic hyperplasia. [NIH] Fixation: 1. The act or operation of holding, suturing, or fastening in a fixed position. 2. The condition of being held in a fixed position. 3. In psychiatry, a term with two related but distinct meanings : (1) arrest of development at a particular stage, which like regression (return to an earlier stage), if temporary is a normal reaction to setbacks and difficulties but if protracted or frequent is a cause of developmental failures and emotional problems, and (2) a close and suffocating attachment to another person, especially a childhood figure, such as one's mother or father. Both meanings are derived from psychoanalytic theory and refer to 'fixation' of libidinal energy either in a specific erogenous zone, hence fixation at the oral, anal, or phallic stage, or in a specific object, hence mother or father fixation. 4. The use of a fixative (q.v.) to preserve histological or cytological specimens. 5. In chemistry, the process whereby a substance is removed from the gaseous or solution phase and localized, as in carbon dioxide fixation or nitrogen fixation. 6. In ophthalmology, direction of the gaze so that the visual image of the object falls on the fovea centralis. 7. In film processing, the chemical removal of all undeveloped salts of the film emulsion, leaving only the developed silver to form a permanent image. [EU] Fluorine: A nonmetallic, diatomic gas that is a trace element and member of the halogen family. It is used in dentistry as flouride to prevent dental caries. [NIH] Flutamide: An antiandrogen with about the same potency as cyproterone in rodent and canine species. [NIH] Folate: A B-complex vitamin that is being studied as a cancer prevention agent. Also called folic acid. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Folic Acid: N-(4-(((2-Amino-1,4-dihydro-4-oxo-6-pteridinyl)methyl)amino)benzoyl)-Lglutamic acid. A member of the vitamin B family that stimulates the hematopoietic system. It is present in the liver and kidney and is found in mushrooms, spinach, yeast, green leaves, and grasses. Folic acid is used in the treatment and prevention of folate deficiencies and megaloblastic anemia. [NIH]

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Follicles: Shafts through which hair grows. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Fovea: The central part of the macula that provides the sharpest vision. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gamma Rays: Very powerful and penetrating, high-energy electromagnetic radiation of shorter wavelength than that of x-rays. They are emitted by a decaying nucleus, usually between 0.01 and 10 MeV. They are also called nuclear x-rays. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Gap Junctions: Connections between cells which allow passage of small molecules and electric current. Gap junctions were first described anatomically as regions of close apposition between cells with a narrow (1-2 nm) gap between cell membranes. The variety in the properties of gap junctions is reflected in the number of connexins, the family of proteins which form the junctions. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gas exchange: Primary function of the lungs; transfer of oxygen from inhaled air into the blood and of carbon dioxide from the blood into the lungs. [NIH] Gastric: Having to do with the stomach. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]

Gastroenteritis: An acute inflammation of the lining of the stomach and intestines, characterized by anorexia, nausea, diarrhoea, abdominal pain, and weakness, which has various causes, including food poisoning due to infection with such organisms as Escherichia coli, Staphylococcus aureus, and Salmonella species; consumption of irritating food or drink; or psychological factors such as anger, stress, and fear. Called also enterogastritis. [EU] Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gastrostomy: Creation of an artificial external opening into the stomach for nutritional support or gastrointestinal compression. [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 Amplification: A selective increase in the number of copies of a gene coding for a specific protein without a proportional increase in other genes. It occurs naturally via the excision of a copy of the repeating sequence from the chromosome and its extrachromosomal replication in a plasmid, or via the production of an RNA transcript of the entire repeating sequence of ribosomal RNA followed by the reverse transcription of the molecule to produce an additional copy of the original DNA sequence. Laboratory techniques have been introduced for inducing disproportional replication by unequal crossing over, uptake of DNA from lysed cells, or generation of extrachromosomal sequences from rolling circle replication. [NIH] Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH]

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Gene Targeting: The integration of exogenous DNA into the genome of an organism at sites where its expression can be suitably controlled. This integration occurs as a result of homologous recombination. [NIH] General practitioner: A medical practitioner who does not specialize in a particular branch of medicine or limit his practice to a specific class of diseases. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genistein: An isoflavonoid derived from soy products. It inhibits protein-tyrosine kinase and topoisomerase-ii (dna topoisomerase (atp-hydrolysing)) activity and is used as an antineoplastic and antitumor agent. Experimentally, it has been shown to induce G2 phase arrest in human and murine cell lines. [NIH] Genital: Pertaining to the genitalia. [EU] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Geriatric: Pertaining to the treatment of the aged. [EU] Germ Cells: The reproductive cells in multicellular organisms. [NIH] Germ Layers: The three layers of cells comprising the early embryo. [NIH] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] Gestational: Psychosis attributable to or occurring during pregnancy. [NIH] Gestational Age: Age of the conceptus. In humans, this may be assessed by medical history, physical examination, early immunologic pregnancy tests, radiography, ultrasonography, and amniotic fluid analysis. [NIH] 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]

Glomerulus: A tiny set of looping blood vessels in the nephron where blood is filtered in the kidney. [NIH] Glucocorticoid: A compound that belongs to the family of compounds called corticosteroids (steroids). Glucocorticoids affect metabolism and have anti-inflammatory and immunosuppressive effects. They may be naturally produced (hormones) or synthetic (drugs). [NIH] Gluconeogenesis: The process by which glucose is formed from a non-carbohydrate source. [NIH]

Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glucose 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

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glucose into a fasting stomach; blood sugar should return to normal in 2 to 21 hours after ingestion. [NIH] Glucose Tolerance Test: Determination of whole blood or plasma sugar in a fasting state before and at prescribed intervals (usually 1/2 hr, 1 hr, 3 hr, 4 hr) after taking a specified amount (usually 100 gm orally) of glucose. [NIH] Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid (glutamate) is the most common excitatory neurotransmitter in the central nervous system. [NIH]

Glutamine: A non-essential amino acid present abundantly throught the body and is involved in many metabolic processes. It is synthesized from glutamic acid and ammonia. It is the principal carrier of nitrogen in the body and is an important energy source for many cells. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Gonad: A sex organ, such as an ovary or a testicle, which produces the gametes in most multicellular animals. [NIH] Gonadal: Pertaining to a gonad. [EU] Gonadorelin: A decapeptide hormone released by the hypothalamus. It stimulates the synthesis and secretion of both follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the pituitary gland. [NIH] Gonadotropin: The water-soluble follicle stimulating substance, by some believed to originate in chorionic tissue, obtained from the serum of pregnant mares. It is used to supplement the action of estrogens. [NIH] Goserelin: 6-(O-(1,1-Dimethylethyl)-D-serine)-10-deglycinamideluteinizing hormonereleasing factor (pig) 2-(aminocarbonyl)hydrazide. A long-acting gonadorelin agonist. It is used in the treatment of malignant neoplasms of the prostate, uterine fibromas, and metastatic breast cancer. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Government Agencies: Administrative units of government responsible for policy making and management of governmental activities in the U.S. and abroad. [NIH] Gp120: 120-kD HIV envelope glycoprotein which is involved in the binding of the virus to its membrane receptor, the CD4 molecule, found on the surface of certain cells in the body. [NIH]

Grade: The grade of a tumor depends on how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread. Grading systems are different for each type of cancer. [NIH] Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Grafting: The operation of transfer of tissue from one site to another. [NIH] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Growth Disorders: Deviations from the average values for a specific age and sex in any or all of the following: height, weight, skeletal proportions, osseous development, or maturation of features. Included here are both acceleration and retardation of growth. [NIH]

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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] Growth Plate: The area between the epiphysis and the diaphysis within which bone growth occurs. [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] Half-Life: The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. [NIH] Haploid: An organism with one basic chromosome set, symbolized by n; the normal condition of gametes in diploids. [NIH] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH] Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Headache Disorders: Common conditions characterized by persistent or recurrent headaches. Headache syndrome classification systems may be based on etiology (e.g., vascular headache, post-traumatic headaches, etc.), temporal pattern (e.g., cluster headache, paroxysmal hemicrania, etc.), and precipitating factors (e.g., cough headache). [NIH] Health 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 Policy: Decisions, usually developed by government policymakers, for determining present and future objectives pertaining to the health care system. [NIH] Health Status: The level of health of the individual, group, or population as subjectively assessed by the individual or by more objective measures. [NIH] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Heart Valves: Flaps of tissue that prevent regurgitation of blood from the ventricles to the atria or from the pulmonary arteries or aorta to the ventricles. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemodialysis: The use of a machine to clean wastes from the blood after the kidneys have failed. The blood travels through tubes to a dialyzer, which removes wastes and extra fluid. The cleaned blood then flows through another set of tubes back into the body. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of

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glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemostasis: The process which spontaneously arrests the flow of blood from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation. [NIH]

Hepatic: Refers to the liver. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]

Heterogenic: Derived from a different source or species. Also called heterogenous. [NIH] Heterogenous: Derived from a different source or species. Also called heterogenic. [NIH] Hirsutism: Excess hair in females and children with an adult male pattern of distribution. The concept does not include hypertrichosis, which is localized or generalized excess hair. [NIH]

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] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormonal therapy: Treatment of cancer by removing, blocking, or adding hormones. Also called hormone therapy or endocrine therapy. [NIH] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Hormone Replacement Therapy: Therapeutic use of hormones to alleviate the effects of hormone deficiency. [NIH] Hormone therapy: Treatment of cancer by removing, blocking, or adding hormones. Also called endocrine therapy. [NIH] Human growth hormone: A protein hormone, secreted by the anterior lobe of the pituitary, which promotes growth of the whole body by stimulating protein synthesis. The human gene has already been cloned and successfully expressed in bacteria. [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] Hydrocortisone: The main glucocorticoid secreted by the adrenal cortex. Its synthetic counterpart is used, either as an injection or topically, in the treatment of inflammation,

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allergy, collagen diseases, asthma, adrenocortical deficiency, shock, and some neoplastic conditions. [NIH] Hydrogel: A network of cross-linked hydrophilic macromolecules used in biomedical applications. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydrophilic: Readily absorbing moisture; hygroscopic; having strongly polar groups that readily interact with water. [EU] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU] Hydroxylation: Hydroxylate, to introduce hydroxyl into (a compound or radical) usually by replacement of hydrogen. [EU] Hydroxylysine: A hydroxylated derivative of the amino acid lysine that is present in certain collagens. [NIH] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hyperandrogenism: A state characterized or caused by an excessive secretion of androgens by the adrenal cortex, ovaries, or testes. The clinical significance in males is negligible, so the term is used most commonly with reference to the female. The common manifestations in women are hirsutism and virilism. It is often caused by ovarian disease (particularly the polycystic ovary syndrome) and by adrenal diseases (particularly adrenal gland hyperfunction). [NIH] Hypercalcemia: Abnormally high level of calcium in the blood. [NIH] Hypercalciuria: Abnormally large amounts of calcium in the urine. [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] Hyperplasia: An increase in the number of cells in a tissue or organ, not due to tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. [NIH] Hyperreactive: Describes a situation in which a body tissue is especially likely to have an exaggerated reaction to a particular situation. [NIH] Hypersecretion: Excessive secretion. [EU] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertelorism: Abnormal increase in the interorbital distance due to overdevelopment of the lesser wings of the sphenoid. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hyperthermia: A type of treatment in which body tissue is exposed to high temperatures to

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damage and kill cancer cells or to make cancer cells more sensitive to the effects of radiation and certain anticancer drugs. [NIH] Hypertriglyceridemia: Condition of elevated triglyceride concentration in the blood; an inherited form occurs in familial hyperlipoproteinemia IIb and hyperlipoproteinemia type IV. It has been linked to higher risk of heart disease and arteriosclerosis. [NIH] Hypertrophy: General increase in bulk of a part or organ, not due to tumor formation, nor to an increase in the number of cells. [NIH] Hypnotic: A drug that acts to induce sleep. [EU] Hypoglycemia: Abnormally low blood sugar [NIH] Hypogonadism: Condition resulting from or characterized by abnormally decreased functional activity of the gonads, with retardation of growth and sexual development. [NIH] Hypophysis: A remnant of the entodermal pouch of Rathke beneath the mucous membrane of the pharynx, which shows pituitary tissue. [NIH] Hypothalamic: Of or involving the hypothalamus. [EU] Hypothalamus: Ventral part of the diencephalon extending from the region of the optic chiasm to the caudal border of the mammillary bodies and forming the inferior and lateral walls of the third ventricle. [NIH] Hysterectomy: Excision of the uterus. [NIH] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Idiopathic: Describes a disease of unknown cause. [NIH] Ifosfamide: Positional isomer of cyclophosphamide which is active as an alkylating agent and an immunosuppressive agent. [NIH] Ileal: Related to the ileum, the lowest end of the small intestine. [NIH] Ileum: The lower end of the small intestine. [NIH] Imaging procedures: Methods of producing pictures of areas inside the body. [NIH] Immaturity: The state or quality of being unripe or not fully developed. [EU] Immune function: Production and action of cells that fight disease or infection. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]

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

effects

of

foreign

Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunogenic: Producing immunity; evoking an immune response. [EU] Immunoglobulin: A protein that acts as an antibody. [NIH] 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] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunotherapy: Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] 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] 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] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Indolent: A type of cancer that grows slowly. [NIH] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] 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]

Infertility: The diminished or absent ability to conceive or produce an offspring while sterility is the complete inability to conceive or produce an offspring. [NIH] Infestation: Parasitic attack or subsistence on the skin and/or its appendages, as by insects, mites, or ticks; sometimes used to denote parasitic invasion of the organs and tissues, as by helminths. [NIH]

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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] 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] Inlay: In dentistry, a filling first made to correspond with the form of a dental cavity and then cemented into the cavity. [NIH] Inorganic: Pertaining to substances not of organic origin. [EU] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Insomnia: Difficulty in going to sleep or getting enough sleep. [NIH] 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] Interferon: A biological response modifier (a substance that can improve the body's natural response to disease). Interferons interfere with the division of cancer cells and can slow tumor growth. There are several types of interferons, including interferon-alpha, -beta, and gamma. These substances are normally produced by the body. They are also made in the laboratory for use in treating cancer and other diseases. [NIH] 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] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Internal Medicine: A medical specialty concerned with the diagnosis and treatment of diseases of the internal organ systems of adults. [NIH] Internal radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called brachytherapy,

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implant radiation, or interstitial radiation therapy. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intestinal: Having to do with the intestines. [NIH] Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intramuscular: IM. Within or into muscle. [NIH] Intramuscular injection: IM. Injection into a 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] Intubation: Introduction of a tube into a hollow organ to restore or maintain patency if obstructed. It is differentiated from catheterization in that the insertion of a catheter is usually performed for the introducing or withdrawing of fluids from the body. [NIH] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]

Involuntary: Reaction occurring without intention or volition. [NIH] Iodine: A nonmetallic element of the halogen group that is represented by the atomic symbol I, atomic number 53, and atomic weight of 126.90. It is a nutritionally essential element, especially important in thyroid hormone synthesis. In solution, it has anti-infective properties and is used topically. [NIH] Ionizing: Radiation comprising charged particles, e. g. electrons, protons, alpha-particles, etc., having sufficient kinetic energy to produce ionization by collision. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Irradiation: The use of high-energy radiation from x-rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive 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] Ischemic stroke: A condition in which the blood supply to part of the brain is cut off. Also called "plug-type" strokes. Blocked arteries starve areas of the brain controlling sight, speech, sensation, and movement so that these functions are partially or completely lost. Ischemic stroke is the most common type of stroke, accounting for 80 percent of all strokes.

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Most ischemic strokes are caused by a blood clot called a thrombus, which blocks blood flow in the arteries feeding the brain, usually the carotid artery in the neck, the major vessel bringing blood to the brain. When it becomes blocked, the risk of stroke is very high. [NIH] Islet: Cell producing insulin in pancreas. [NIH] Jejunostomy: Surgical formation of an opening through the abdominal wall into the jejunum, usually for enteral hyperalimentation. [NIH] Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Ketoconazole: Broad spectrum antifungal agent used for long periods at high doses, especially in immunosuppressed patients. [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] Kinetic: Pertaining to or producing motion. [EU] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Lactation: The period of the secretion of milk. [EU] Laparoscopy: Examination, therapy or surgery of the abdomen's interior by means of a laparoscope. [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 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] 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]

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Leiomyoma: A benign tumor derived from smooth muscle tissue, also known as a fibroid tumor. They rarely occur outside of the uterus and the gastrointestinal tract but can occur in the skin and subcutaneous tissues, probably arising from the smooth muscle of small blood vessels in these tissues. [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] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Leuprolide: A potent and long acting analog of naturally occurring gonadotropin-releasing hormone (gonadorelin). Its action is similar to gonadorelin, which regulates the synthesis and release of pituitary gonadotropins. [NIH] Libido: The psychic drive or energy associated with sexual instinct in the broad sense (pleasure and love-object seeking). It may also connote the psychic energy associated with instincts in general that motivate behavior. [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]

Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] Ligands: A RNA simulation method developed by the MIT. [NIH] Linkage: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Lipid: Fat. [NIH] Lipid A: Lipid A is the biologically active component of lipopolysaccharides. It shows strong endotoxic activity and exhibits immunogenic properties. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] Lipolysis: The hydrolysis of lipids. [NIH] Lipopolysaccharides: Substance consisting of polysaccaride and lipid. [NIH] Lipoprotein: Any of the lipid-protein complexes in which lipids are transported in the blood; lipoprotein particles consist of a spherical hydrophobic core of triglycerides or cholesterol esters surrounded by an amphipathic monolayer of phospholipids, cholesterol, and apolipoproteins; the four principal classes are high-density, low-density, and very-lowdensity lipoproteins and chylomicrons. [EU] 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]

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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] Lobe: A portion of an organ such as the liver, lung, breast, or brain. [NIH] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Longitudinal study: Also referred to as a "cohort study" or "prospective study"; the analytic method of epidemiologic study in which subsets of a defined population can be identified who are, have been, or in the future may be exposed or not exposed, or exposed in different degrees, to a factor or factors hypothesized to influence the probability of occurrence of a given disease or other outcome. The main feature of this type of study is to observe large numbers of subjects over an extended time, with comparisons of incidence rates in groups that differ in exposure levels. [NIH] Loop: A wire usually of platinum bent at one end into a small loop (usually 4 mm inside diameter) and used in transferring microorganisms. [NIH] Low-density lipoprotein: Lipoprotein that contains most of the cholesterol in the blood. LDL carries cholesterol to the tissues of the body, including the arteries. A high level of LDL increases the risk of heart disease. LDL typically contains 60 to 70 percent of the total serum cholesterol and both are directly correlated with CHD risk. [NIH] Lumbar: Pertaining to the loins, the part of the back between the thorax and the pelvis. [EU] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [NIH] Lutein Cells: The cells of the corpus luteum which are derived from the granulosa cells and the theca cells of the Graafian follicle. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]

Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] Lymphoblastic: One of the most aggressive types of non-Hodgkin lymphoma. [NIH] Lymphoblasts: Interferon produced predominantly by leucocyte cells. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] Lymphocytic: Referring to lymphocytes, a type of white blood cell. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH]

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Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [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] 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] Malabsorption: Impaired intestinal absorption of nutrients. [EU] Malabsorption syndrome: A group of symptoms such as gas, bloating, abdominal pain, and diarrhea resulting from the body's inability to properly absorb nutrients. [NIH] 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] Mandible: The largest and strongest bone of the face constituting the lower jaw. It supports the lower teeth. [NIH] Man-made: Ionizing radiation emitted by artificial or concentrated natural, radioactive material or resulting from the operation of high voltage apparatus, such as X-ray apparatus or particle accelerators, of nuclear reactors, or from nuclear explosions. [NIH] Mastectomy: Surgery to remove the breast (or as much of the breast tissue as possible). [NIH] Maternal Exposure: Exposure of the female parent, human or animal, to potentially harmful chemical, physical, or biological agents in the environment or to environmental factors that may include ionizing radiation, pathogenic organisms, or toxic chemicals that may affect offspring. It includes pre-conception maternal exposure. [NIH] Maximum Tolerated Dose: The highest dose level eliciting signs of toxicity without having major effects on survival relative to the test in which it is used. [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 oncologist: A doctor who specializes in diagnosing and treating cancer using chemotherapy, hormonal therapy, and biological therapy. A medical oncologist often serves as the main caretaker of someone who has cancer and coordinates treatment provided by other specialists. [NIH] Medical Records: Recording of pertinent information concerning patient's illness or illnesses. [NIH] Medical Staff: Professional medical personnel who provide care to patients in an organized facility, institution or agency. [NIH] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH]

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Medroxyprogesterone: (6 alpha)-17-Hydroxy-6-methylpregn-4-ene-3,20-dione. A synthetic progestational hormone used in veterinary practice as an estrus regulator. [NIH] Medroxyprogesterone Acetate: An injectable contraceptive, generally marketed under the name Depo-Provera. [NIH] Megestrol: 17-Hydroxy-6-methylpregna-3,6-diene-3,20-dione. A progestational hormone used most commonly as the acetate ester. As the acetate, it is more potent than progesterone both as a progestagen and as an ovulation inhibitor. It has also been used in the palliative treatment of breast cancer. [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] Membrane: A very thin layer of tissue that covers a surface. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Menarche: The establishment or beginning of the menstrual function. [EU] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Menopause: Permanent cessation of menstruation. [NIH] Menorrhagia: Excessive menstrual flow. [NIH] Menstrual Cycle: The period of the regularly recurring physiologic changes in the endometrium occurring during the reproductive period in human females and some primates and culminating in partial sloughing of the endometrium (menstruation). [NIH] Menstruation: The normal physiologic discharge through the vagina of blood and mucosal tissues from the nonpregnant uterus. [NIH] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH] Mental Retardation: Refers to sub-average general intellectual functioning which originated during the developmental period and is associated with impairment in adaptive behavior. [NIH]

Mentors: Senior professionals who provide guidance, direction and support to those persons desirous of improvement in academic positions, administrative positions or other career development situations. [NIH] Meta-Analysis: A quantitative method of combining the results of independent studies (usually drawn from the published literature) and synthesizing summaries and conclusions which may be used to evaluate therapeutic effectiveness, plan new studies, etc., with application chiefly in the areas of research and medicine. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors" and contain cells that are like those in the original (primary) tumor. The plural is metastases. [NIH] Metastatic: Having to do with metastasis, which is the spread of cancer from one part of the body to another. [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of

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the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Microtubules: Slender, cylindrical filaments found in the cytoskeleton of plant and animal cells. They are composed of the protein tubulin. [NIH] Midaxillary line: An imaginary vertical line that passes midway between the anterior and posterior axillary (armpit) folds. [NIH] Milliliter: A measure of volume for a liquid. A milliliter is approximately 950-times smaller than a quart and 30-times smaller than a fluid ounce. A milliliter of liquid and a cubic centimeter (cc) of liquid are the same. [NIH] Millimeter: A measure of length. A millimeter is approximately 26-times smaller than an inch. [NIH] Mineralization: The action of mineralizing; the state of being mineralized. [EU] Minority Groups: A subgroup having special characteristics within a larger group, often bound together by special ties which distinguish it from the larger group. [NIH] Mitochondrial Swelling: Increase in volume of mitochondria due to an influx of fluid; it occurs in hypotonic solutions due to osmotic pressure and in isotonic solutions as a result of altered permeability of the membranes of respiring mitochondria. [NIH] 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] Mitotic: Cell resulting from mitosis. [NIH] Mitotic inhibitors: Drugs that kill cancer cells by interfering with cell division (mitostis). [NIH]

Mitoxantrone: An anthracenedione-derived antineoplastic agent. [NIH] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] 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,

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pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monoclonal antibodies: Laboratory-produced substances that can locate and bind to cancer cells wherever they are in the body. Many monoclonal antibodies are used in cancer detection or therapy; each one recognizes a different protein on certain cancer cells. Monoclonal antibodies can be used alone, or they can be used to deliver drugs, toxins, or radioactive material directly to a tumor. [NIH] Monocyte: A type of white blood cell. [NIH] Monotherapy: A therapy which uses only one drug. [EU] 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] Morula: The early embryo at the developmental stage in which the blastomeres, resulting from repeated mitotic divisions of the fertilized ovum, form a compact mass. [NIH] Motility: The ability to move spontaneously. [EU] Mucosa: A mucous membrane, or tunica mucosa. [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] Myocardial Ischemia: A disorder of cardiac function caused by insufficient blood flow to the muscle tissue of the heart. The decreased blood flow may be due to narrowing of the coronary arteries (coronary arteriosclerosis), to obstruction by a thrombus (coronary thrombosis), or less commonly, to diffuse narrowing of arterioles and other small vessels within the heart. Severe interruption of the blood supply to the myocardial tissue may result in necrosis of cardiac muscle (myocardial infarction). [NIH] Myocardial Reperfusion: Generally, restoration of blood supply to heart tissue which is ischemic due to decrease in normal blood supply. The decrease may result from any source including atherosclerotic obstruction, narrowing of the artery, or surgical clamping. Reperfusion can be induced to treat ischemia. Methods include chemical dissolution of an occluding thrombus, administration of vasodilator drugs, angioplasty, catheterization, and artery bypass graft surgery. However, it is thought that reperfusion can itself further damage the ischemic tissue, causing myocardial reperfusion injury. [NIH] Myocardial Reperfusion Injury: Functional, metabolic, or structural changes in ischemic heart muscle thought to result from reperfusion to the ischemic areas. Changes can be fatal to muscle cells and may include edema with explosive cell swelling and disintegration, sarcolemma disruption, fragmentation of mitochondria, contraction band necrosis, enzyme washout, and calcium overload. Other damage may include hemorrhage and ventricular arrhythmias. One possible mechanism of damage is thought to be oxygen free radicals. Treatment currently includes the introduction of scavengers of oxygen free radicals, and injury is thought to be prevented by warm blood cardioplegic infusion prior to reperfusion. [NIH]

Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Nadir: The lowest point; point of greatest adversity or despair. [EU] Nafarelin: 6-(3-(2-Naphthalenyl)-D-alanine)luteinizing hormone-releasing factor (pig). A

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gonadorelin analog agonist. It has been used in the treatment of central precocious puberty and endometriosis. [NIH] Naive: Used to describe an individual who has never taken a certain drug or class of drugs (e. g., AZT-naive, antiretroviral-naive), or to refer to an undifferentiated immune system cell. [NIH] Nasal Cavity: The proximal portion of the respiratory passages on either side of the nasal septum, lined with ciliated mucosa, extending from the nares to the pharynx. [NIH] Nasal Mucosa: The mucous membrane lining the nasal cavity. [NIH] Nasogastric: The process of passing a small, flexible plastic tube through the nose or mouth into the stomach or small intestine. [NIH] Natural 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] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU] Neoplasia: Abnormal and uncontrolled cell growth. [NIH] Neoplasms: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms. [NIH] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] Nephrectomy: Surgery to remove a kidney. Radical nephrectomy removes the kidney, the adrenal gland, nearby lymph nodes, and other surrounding tissue. Simple nephrectomy removes only the kidney. Partial nephrectomy removes the tumor but not the entire kidney. [NIH]

Nephron: A tiny part of the kidneys. Each kidney is made up of about 1 million nephrons, which are the working units of the kidneys, removing wastes and extra fluids from the blood. [NIH] Nephropathy: Disease of the kidneys. [EU] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis,

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as the neutral arch. [EU] Neuroendocrine: Having to do with the interactions between the nervous system and the endocrine system. Describes certain cells that release hormones into the blood in response to stimulation of the nervous system. [NIH] Neurologic: Having to do with nerves or the nervous system. [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] Neurophysiology: The scientific discipline concerned with the physiology of the nervous system. [NIH] Neuroprotective Agents: Drugs intended to prevent damage to the brain or spinal cord from ischemia, stroke, convulsions, or trauma. Some must be administered before the event, but others may be effective for some time after. They act by a variety of mechanisms, but often directly or indirectly minimize the damage produced by endogenous excitatory amino acids. [NIH] Neuropsychological Tests: Tests designed to assess neurological function associated with certain behaviors. They are used in diagnosing brain dysfunction or damage and central nervous system disorders or injury. [NIH] Neurosciences: The scientific disciplines concerned with the embryology, anatomy, physiology, biochemistry, pharmacology, etc., of the nervous sytem. [NIH] Neurosecretory Systems: A system of neurons that has the specialized function to produce and secrete hormones, and that constitutes, in whole or in part, an endocrine organ or system. [NIH] 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] Nilutamide: A drug that blocks the effects of male hormones in the body. It belongs to the family of drugs called antiandrogens. [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] Node-negative: Cancer that has not spread to the lymph nodes. [NIH] Node-positive: Cancer that has spread to the lymph nodes. [NIH] Noonan Syndrome: A multifaceted disorder due to a basic defect of connective tissue. It is characterized by short stature, webbed neck, ptosis, skeletal malformations, hypertelorism, hormonal imbalance, cryptorchidism, multiple cardiac abnormalities (most commonly

234 Hormone Therapy

including pulmonary valve stenosis), and some degree of mental retardation. The phenotype resembles that of Turner's syndrome; however, Noonan syndrome occurs in both males and females, and no chromosomal abnormality has been found. Nevertheless, familial studies suggest that the trait is inherited as an autosomal dominant. [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] 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] Nurse Practitioners: Nurses who are specially trained to assume an expanded role in providing medical care under the supervision of a physician. [NIH] Nutritional Status: State of the body in relation to the consumption and utilization of nutrients. [NIH] Observational study: An epidemiologic study that does not involve any intervention, experimental or otherwise. Such a study may be one in which nature is allowed to take its course, with changes in one characteristic being studied in relation to changes in other characteristics. Analytical epidemiologic methods, such as case-control and cohort study designs, are properly called observational epidemiology because the investigator is observing without intervention other than to record, classify, count, and statistically analyze results. [NIH] Oestradiol: Growth hormone. [NIH] Ointments: Semisolid preparations used topically for protective emollient effects or as a vehicle for local administration of medications. Ointment bases are various mixtures of fats, waxes, animal and plant oils and solid and liquid hydrocarbons. [NIH] Oligomenorrhea: Abnormally infrequent menstruation. [NIH] Oliguria: Clinical manifestation of the urinary system consisting of a decrease in the amount of urine secreted. [NIH] Oncologist: A doctor who specializes in treating cancer. Some oncologists specialize in a particular type of cancer treatment. For example, a radiation oncologist specializes in treating cancer with radiation. [NIH] Oncology: The study of cancer. [NIH] Oocytes: Female germ cells in stages between the prophase of the first maturation division and the completion of the second maturation division. [NIH] Opacity: Degree of density (area most dense taken for reading). [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] 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]

Orchiectomy: The surgical removal of one or both testicles. [NIH]

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Osseointegration: The growth action of bone tissue, as it assimilates surgically implanted devices or prostheses to be used as either replacement parts (e.g., hip) or as anchors (e.g., endosseous dental implants). [NIH] Ossification: The formation of bone or of a bony substance; the conversion of fibrous tissue or of cartilage into bone or a bony substance. [EU] Osteoarthritis: Degeneration of articular cartilage. Primary osteoarthritis is very common in older persons, especially affecting weight-bearing joints. Articular cartilage becomes soft, frayed and thinned. [NIH] Osteogenesis: The histogenesis of bone including ossification. It occurs continuously but particularly in the embryo and child and during fracture repair. [NIH] Osteogenesis Imperfecta: A collagen disorder resulting from defective biosynthesis of type I collagen and characterized by brittle, osteoporotic, and easily fractured bones. It may also present with blue sclerae, loose joints, and imperfect dentin formation. There are four major types, I-IV. [NIH] Osteoporosis: Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal osteoporosis and age-related (or senile) osteoporosis. [NIH] Outpatient: A patient who is not an inmate of a hospital but receives diagnosis or treatment in a clinic or dispensary connected with the hospital. [NIH] Ovarian Hyperstimulation Syndrome: Syndrome composed of a combination of ovarian enlargement and an acute fluid shift out of the intravascular space. The enlargement is caused by ovarian cyst formation and the fluid shift may result in ascites, hydrothorax, or generalized edema. The syndrome is most usually seen as a complication of ovulation induction, a treatment for infertility. [NIH] Ovaries: The pair of female reproductive glands in which the ova, or eggs, are formed. The ovaries are located in the pelvis, one on each side of the uterus. [NIH] Ovary: Either of the paired glands in the female that produce the female germ cells and secrete some of the female sex hormones. [NIH] Overall survival: The percentage of subjects in a study who have survived for a defined period of time. Usually reported as time since diagnosis or treatment. Often called the survival rate. [NIH] Overexpress: An excess of a particular protein on the surface of a cell. [NIH] Ovulation: The discharge of a secondary oocyte from a ruptured graafian follicle. [NIH] Ovulation Induction: Techniques for the artifical induction of ovulation. [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]

Oxidation-Reduction: A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471). [NIH]

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Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). [NIH] Oxygen Consumption: The oxygen consumption is determined by calculating the difference between the amount of oxygen inhaled and exhaled. [NIH] Pacemaker: An object or substance that influences the rate at which a certain phenomenon occurs; often used alone to indicate the natural cardiac pacemaker or an artificial cardiac pacemaker. In biochemistry, a substance whose rate of reaction sets the pace for a series of interrelated reactions. [EU] Paclitaxel: Antineoplastic agent isolated from the bark of the Pacific yew tree, Taxus brevifolia. Paclitaxel stabilizes microtubules in their polymerized form and thus mimics the action of the proto-oncogene proteins c-mos. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Pamidronate: A drug that belongs to the family of drugs called bisphosphonates. Pamidronate is used as treatment for abnormally high levels of calcium in the blood. [NIH] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Pancreatic Insufficiency: Absence of or reduced pancreatic exocrine secretion into the duodenum and resultant poor digestion of lipids, vitamins, nitrogen, and carbohydrates. [NIH]

Paraffin: A mixture of solid hydrocarbons obtained from petroleum. It has a wide range of uses including as a stiffening agent in ointments, as a lubricant, and as a topical antiinflammatory. It is also commonly used as an embedding material in histology. [NIH] Parathyroid: 1. Situated beside the thyroid gland. 2. One of the parathyroid glands. 3. A sterile preparation of the water-soluble principle(s) of the parathyroid glands, ad-ministered parenterally as an antihypocalcaemic, especially in the treatment of acute hypoparathyroidism with tetany. [EU] Parathyroid Glands: Two small paired endocrine glands in the region of the thyroid gland. They secrete parathyroid hormone and are concerned with the metabolism of calcium and phosphorus. [NIH] Parathyroid hormone: A substance made by the parathyroid gland that helps the body store and use calcium. Also called parathormone, parathyrin, or PTH. [NIH] Parenteral: Not through the alimentary canal but rather by injection through some other route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intravenous, etc. [EU] Parenteral Nutrition: The administering of nutrients for assimilation and utilization by a patient who cannot maintain adequate nutrition by enteral feeding alone. Nutrients are administered by a route other than the alimentary canal (e.g., intravenously, subcutaneously). [NIH] Partial remission: The shrinking, but not complete disappearance, of a tumor in response to therapy. Also called partial response. [NIH] Parturition: The act or process of given birth to a child. [EU]

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Patch: A piece of material used to cover or protect a wound, an injured part, etc.: a patch over the eye. [NIH] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]

Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Patient Compliance: Voluntary cooperation of the patient in following a prescribed regimen. [NIH] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]

Pectins: High molecular weight polysaccharides present in the cell walls of all plants. Pectins cement cell walls together. They are used as emulsifiers and stabilizers in the food industry. They have been tried for a variety of therpeutic uses including as antidiarreals, where they are now generally considered ineffective, and in the treatment of hypercholesterolemia. [NIH] Pediatric Endocrinologist: A doctor who sees and treats children with problems of the endocrine glands; diabetes is an endocrine disorder. [NIH] Pelvic: Pertaining to the pelvis. [EU] Penicillin: An antibiotic drug used to treat infection. [NIH] Penis: The external reproductive organ of males. It is composed of a mass of erectile tissue enclosed in three cylindrical fibrous compartments. Two of the three compartments, the corpus cavernosa, are placed side-by-side along the upper part of the organ. The third compartment below, the corpus spongiosum, houses the urethra. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Peptide T: N-(N-(N(2)-(N-(N-(N-(N-D-Alanyl L-seryl)-L-threonyl)-L-threonyl) L-threonyl)L-asparaginyl)-L-tyrosyl) L-threonine. Octapeptide sharing sequence homology with HIV envelope protein gp120. It is potentially useful as antiviral agent in AIDS therapy. The core pentapeptide sequence, TTNYT, consisting of amino acids 4-8 in peptide T, is the HIV envelope sequence required for attachment to the CD4 receptor. [NIH] Perception: The ability quickly and accurately to recognize similarities and differences among presented objects, whether these be pairs of words, pairs of number series, or multiple sets of these or other symbols such as geometric figures. [NIH] Percutaneous: Performed through the skin, as injection of radiopacque material in radiological examination, or the removal of tissue for biopsy accomplished by a needle. [EU] Perinatal: Pertaining to or occurring in the period shortly before and after birth; variously defined as beginning with completion of the twentieth to twenty-eighth week of gestation and ending 7 to 28 days after birth. [EU] Perineal: Pertaining to the perineum. [EU] Periodontal disease: Disease involving the supporting structures of the teeth (as the gums and periodontal membranes). [NIH] Periodontitis: Inflammation of the periodontal membrane; also called periodontitis simplex.

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[NIH]

Peripheral blood: Blood circulating throughout the body. [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 stem cell transplantation: A method of replacing blood-forming cells destroyed by cancer treatment. Immature blood cells (stem cells) in the circulating blood that are similar to those in the bone marrow are given after treatment to help the bone marrow recover and continue producing healthy blood cells. Transplantation may be autologous (an individual's own blood cells saved earlier), allogeneic (blood cells donated by someone else), or syngeneic (blood cells donated by an identical twin). Also called peripheral stem cell support. [NIH] Peritoneal: Having to do with the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Peritoneal Cavity: The space enclosed by the peritoneum. It is divided into two portions, the greater sac and the lesser sac or omental bursa, which lies behind the stomach. The two sacs are connected by the foramen of Winslow, or epiploic foramen. [NIH] Peritoneal Dialysis: Dialysis fluid being introduced into and removed from the peritoneal cavity as either a continuous or an intermittent procedure. [NIH] Peritoneum: Endothelial lining of the abdominal cavity, the parietal peritoneum covering the inside of the abdominal wall and the visceral peritoneum covering the bowel, the mesentery, and certain of the organs. The portion that covers the bowel becomes the serosal layer of the bowel wall. [NIH] Petroleum: Naturally occurring complex liquid hydrocarbons which, after distillation, yield combustible fuels, petrochemicals, and lubricants. [NIH] PH: The symbol relating the hydrogen ion (H+) concentration or activity of a solution to that of a given standard solution. Numerically the pH is approximately equal to the negative logarithm of H+ concentration expressed in molarity. pH 7 is neutral; above it alkalinity increases and below it acidity increases. [EU] Phallic: Pertaining to the phallus, or penis. [EU] Pharmaceutical Preparations: Drugs intended for human or veterinary use, presented in their finished dosage form. Included here are materials used in the preparation and/or formulation of the finished dosage form. [NIH] Pharmaceutical Solutions: Homogeneous liquid preparations that contain one or more chemical substances dissolved, i.e., molecularly dispersed, in a suitable solvent or mixture of mutually miscible solvents. For reasons of their ingredients, method of preparation, or use, they do not fall into another group of products. [NIH] 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] Phosphates: Inorganic salts of phosphoric acid. [NIH]

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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] Phosphoprotein Phosphatase: A group of enzymes removing the serine- or threoninebound phosphate groups from a wide range of phosphoproteins, including a number of enzymes which have been phosphorylated under the action of a kinase. (Enzyme Nomenclature, 1992) EC 3.1.3.16. [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] Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. [NIH] Photocoagulation: Using a special strong beam of light (laser) to seal off bleeding blood vessels such as in the eye. The laser can also burn away blood vessels that should not have grown in the eye. This is the main treatment for diabetic retinopathy. [NIH] Physical Examination: Systematic and thorough inspection of the patient for physical signs of disease or abnormality. [NIH] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]

Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Pilot study: The initial study examining a new method or treatment. [NIH] Pineal Body: A small conical midline body attached to the posterior part of the third ventricle and lying between the superior colliculi, below the splenium of the corpus callosum. [NIH] Pineal gland: A tiny organ located in the cerebrum that produces melatonin. Also called pineal body or pineal organ. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [NIH] Placenta: A highly vascular fetal organ through which the fetus absorbs oxygen and other nutrients and excretes carbon dioxide and other wastes. It begins to form about the eighth day of gestation when the blastocyst adheres to the decidua. [NIH] Placental Insufficiency: Failure of the placenta to deliver an adequate supply of nutrients and oxygen to the fetus. [NIH] Plague: An acute infectious disease caused by Yersinia pestis that affects humans, wild rodents, and their ectoparasites. This condition persists due to its firm entrenchment in sylvatic rodent-flea ecosystems throughout the world. Bubonic plague is the most common form. [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

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destruction of bacterial cells by a bacteriophage. The concentration of infective virus in a fluid can be estimated by applying the fluid to a culture and counting the number of. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasma protein: One of the hundreds of different proteins present in blood plasma, including carrier proteins ( such albumin, transferrin, and haptoglobin), fibrinogen and other coagulation factors, complement components, immunoglobulins, enzyme inhibitors, precursors of substances such as angiotension and bradykinin, and many other types of proteins. [EU] Plasmid: An autonomously replicating, extra-chromosomal DNA molecule found in many bacteria. Plasmids are widely used as carriers of cloned genes. [NIH] Plasmin: A product of the lysis of plasminogen (profibrinolysin) by plasminogen activators. It is composed of two polypeptide chains, light (B) and heavy (A), with a molecular weight of 75,000. It is the major proteolytic enzyme involved in blood clot retraction or the lysis of fibrin and quickly inactivated by antiplasmins. EC 3.4.21.7. [NIH] Plasminogen: Precursor of fibrinolysin (plasmin). It is a single-chain beta-globulin of molecular weight 80-90,000 found mostly in association with fibrinogen in plasma; plasminogen activators change it to fibrinolysin. It is used in wound debriding and has been investigated as a thrombolytic agent. [NIH] 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. Also called thrombocytes. [NIH] Platinum: Platinum. A heavy, soft, whitish metal, resembling tin, atomic number 78, atomic weight 195.09, symbol Pt. (From Dorland, 28th ed) It is used in manufacturing equipment for laboratory and industrial use. It occurs as a black powder (platinum black) and as a spongy substance (spongy platinum) and may have been known in Pliny's time as "alutiae". [NIH]

Ploidy: The number of sets of chromosomes in a cell or an organism. For example, haploid means one set and diploid means two sets. [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Policy Making: The decision process by which individuals, groups or institutions establish policies pertaining to plans, programs or procedures. [NIH] Polycystic: An inherited disorder characterized by many grape-like clusters of fluid-filled cysts that make both kidneys larger over time. These cysts take over and destroy working kidney tissue. PKD may cause chronic renal failure and end-stage renal disease. [NIH] Polycystic Ovary Syndrome: Clinical symptom complex characterized by oligomenorrhea

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or amenorrhea, anovulation, and regularly associated with bilateral polycystic ovaries. [NIH] Polyethylene: A vinyl polymer made from ethylene. It can be branched or linear. Branched or low-density polyethylene is tough and pliable but not to the same degree as linear polyethylene. Linear or high-density polyethylene has a greater hardness and tensile strength. Polyethylene is used in a variety of products, including implants and prostheses. [NIH]

Polyethylene Glycols: Alpha-Hydro-omega-hydroxypoly(oxy-1,2-ethanediyls). Additional polymers of ethylene oxide and water and their ethers. They vary in consistency from liquid to solid, depending on the molecular weight, indicated by a number following the name. Used as surfactants in industry, including foods, cosmetics and pharmaceutics; in biomedicine, as dispersing agents, solvents, ointment and suppository bases, vehicles, tablet excipients. Some specific groups are lauromagrogols, nonoxynols, octoxynols and poloxamers. [NIH] Polymers: Compounds formed by the joining of smaller, usually repeating, units linked by covalent bonds. These compounds often form large macromolecules (e.g., polypeptides, proteins, plastics). [NIH] 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] Polyposis: The development of numerous polyps (growths that protrude from a mucous membrane). [NIH] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Population Growth: Increase, over a specific period of time, in the number of individuals living in a country or region. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postmenopausal: Refers to the time after menopause. Menopause is the time in a woman's life when menstrual periods stop permanently; also called "change of life." [NIH] Postnatal: Occurring after birth, with reference to the newborn. [EU] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Post-translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Post-traumatic: Occurring as a result of or after injury. [EU] Potentiates: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Precancerous: A term used to describe a condition that may (or is likely to) become cancer. Also called premalignant. [NIH] Preclinical: Before a disease becomes clinically recognizable. [EU]

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Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Predisposition: A latent susceptibility to disease which may be activated under certain conditions, as by stress. [EU] Prednisolone: A glucocorticoid with the general properties of the corticosteroids. It is the drug of choice for all conditions in which routine systemic corticosteroid therapy is indicated, except adrenal deficiency states. [NIH] Prednisone: A synthetic anti-inflammatory glucocorticoid derived from cortisone. It is biologically inert and converted to prednisolone in the liver. [NIH] Pregnancy Outcome: Results of conception and ensuing pregnancy, including live birth, stillbirth, spontaneous abortion, induced abortion. The outcome may follow natural or artificial insemination or any of the various reproduction techniques, such as embryo transfer or fertilization in vitro. [NIH] Pregnancy Tests: Tests to determine whether or not an individual is pregnant. [NIH] Pregnenolone: Steroid hormone. [NIH] Premalignant: A term used to describe a condition that may (or is likely to) become cancer. Also called precancerous. [NIH] Premenopausal: Refers to the time before menopause. Menopause is the time of life when a women's menstrual periods stop permanently; also called "change of life." [NIH] Premenstrual: Occurring before menstruation. [EU] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Pressoreceptors: Receptors in the vascular system, particularly the aorta and carotid sinus, which are sensitive to stretch of the vessel walls. [NIH] Presynaptic: Situated proximal to a synapse, or occurring before the synapse is crossed. [EU] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Primary endpoint: The main result that is measured at the end of a study to see if a given treatment worked (e.g., the number of deaths or the difference in survival between the treatment group and the control group). What the primary endpoint will be is decided before the study begins. [NIH] Primary Prevention: Prevention of disease or mental disorders in susceptible individuals or populations through promotion of health, including mental health, and specific protection, as in immunization, as distinguished from the prevention of complications or after-effects of existing disease. [NIH] Primary tumor: The original tumor. [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] Progesterone: Pregn-4-ene-3,20-dione. The principal progestational hormone of the body, secreted by the corpus luteum, adrenal cortex, and placenta. Its chief function is to prepare the uterus for the reception and development of the fertilized ovum. It acts as an antiovulatory agent when administered on days 5-25 of the menstrual cycle. [NIH] Progestogen: A term applied to any substance possessing progestational activity. [EU]

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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] Prolactin: Pituitary lactogenic hormone. A polypeptide hormone with a molecular weight of about 23,000. It is essential in the induction of lactation in mammals at parturition and is synergistic with estrogen. The hormone also brings about the release of progesterone from lutein cells, which renders the uterine mucosa suited for the embedding of the ovum should fertilization occur. [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] Prophase: The first phase of cell division, in which the chromosomes become visible, the nucleus starts to lose its identity, the spindle appears, and the centrioles migrate toward opposite poles. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Proportional: Being in proportion : corresponding in size, degree, or intensity, having the same or a constant ratio; of, relating to, or used in determining proportions. [EU] Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Prostate gland: A gland in the male reproductive system just below the bladder. It surrounds part of the urethra, the canal that empties the bladder, and produces a fluid that forms part of semen. [NIH] Prostatectomy: Complete or partial surgical removal of the prostate. Three primary approaches are commonly employed: suprapubic - removal through an incision above the pubis and through the urinary bladder; retropubic - as for suprapubic but without entering the urinary bladder; and transurethral (transurethral resection of prostate). [NIH] Prostatic Hyperplasia: Enlargement or overgrowth of the prostate gland as a result of an increase in the number of its constituent cells. [NIH] Prostatic Intraepithelial Neoplasia: A premalignant change arising in the prostatic epithelium, regarded as the most important and most likely precursor of prostatic adenocarcinoma. The neoplasia takes the form of an intra-acinar or ductal proliferation of secretory cells with unequivocal nuclear anaplasia, which corresponds to nuclear grade 2 and 3 invasive prostate cancer. [NIH] Prostatic Neoplasms: Tumors or cancer of the prostate. [NIH] Prostatitis: Inflammation of the prostate. [EU] 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]

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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] Protein-Tyrosine Kinase: An enzyme that catalyzes the phosphorylation of tyrosine residues in proteins with ATP or other nucleotides as phosphate donors. EC 2.7.1.112. [NIH] Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Prothrombin: A plasma protein that is the inactive precursor of thrombin. It is converted to thrombin by a prothrombin activator complex consisting of factor Xa, factor V, phospholipid, and calcium ions. Deficiency of prothrombin leads to hypoprothrombinemia. [NIH]

Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Proto-Oncogene Proteins: Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity. [NIH] Proto-Oncogene Proteins c-mos: Cellular proteins encoded by the c-mos genes. They function in the cell cycle to maintain maturation promoting factor in the active state and have protein-serine/threonine kinase activity. Oncogenic transformation can take place when c-mos proteins are expressed at the wrong time. [NIH] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Ptosis: 1. Prolapse of an organ or part. 2. Drooping of the upper eyelid from paralysis of the third nerve or from sympathetic innervation. [EU] Puberty: The period during which the secondary sex characteristics begin to develop and the capability of sexual reproduction is attained. [EU] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] 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 Valve: A valve situated at the entrance to the pulmonary trunk from the right

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ventricle. [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]

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] Quinones: Hydrocarbon rings which contain two ketone moieties in any position. They can be substituted in any position except at the ketone groups. [NIH] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Radial Artery: The direct continuation of the brachial trunk, originating at the bifurcation of the brachial artery opposite the neck of the radius. Its branches may be divided into three groups corresponding to the three regions in which the vessel is situated, the forearm, wrist, and hand. [NIH] 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 oncologist: A doctor who specializes in using radiation to treat cancer. [NIH] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH] Radical prostatectomy: Surgery to remove the entire prostate. The two types of radical prostatectomy are retropubic prostatectomy and perineal prostatectomy. [NIH] Radioactive: Giving off radiation. [NIH] Radiography: Examination of any part of the body for diagnostic purposes by means of roentgen rays, recording the image on a sensitized surface (such as photographic film). [NIH] Radioimmunotherapy: Radiotherapy where cytotoxic radionuclides are linked to antibodies in order to deliver toxins directly to tumor targets. Therapy with targeted radiation rather than antibody-targeted toxins (immunotoxins) has the advantage that adjacent tumor cells, which lack the appropriate antigenic determinants, can be destroyed by radiation cross-fire. Radioimmunotherapy is sometimes called targeted radiotherapy, but this latter term can also refer to radionuclides linked to non-immune molecules (radiotherapy). [NIH] Radioisotope: An unstable element that releases radiation as it breaks down. Radioisotopes can be used in imaging tests or as a treatment for cancer. [NIH] Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH] Radiological: Pertaining to radiodiagnostic and radiotherapeutic procedures, and interventional radiology or other planning and guiding medical radiology. [NIH] 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]

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Radius: The lateral bone of the forearm. [NIH] Raloxifene: A second generation selective estrogen receptor modulator (SERM) used to prevent osteoporosis in postmenopausal women. It has estrogen agonist effects on bone and cholesterol metabolism but behaves as a complete estrogen antagonist on mammary gland and uterine tissue. [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] 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] Receptor, Insulin: A cell surface receptor for insulin. It is comprised of a tetramer of two alpha and two beta subunits which are derived from cleavage of a single precusor protein. The receptor contains an intrinsic tyrosine kinase domain that is located within the beta subunit. Activation of the receptor by insulin results in numerous metabolic changes including increased uptake of glucose into the liver, muscle, and adipose tissue. EC 2.7.11.-. [NIH]

Receptors, Serotonin: Cell-surface proteins that bind serotonin and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Recovery of Function: A partial or complete return to the normal or proper physiologic activity of an organ or part following disease or trauma. [NIH] Rectal: By or having to do with the rectum. The rectum is the last 8 to 10 inches of the large intestine and ends at the anus. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH]

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Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Refractory: Not readily yielding to treatment. [EU] Regeneration: The natural renewal of a structure, as of a lost tissue or part. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Relapse: The return of signs and symptoms of cancer after a period of improvement. [NIH] Relaxin: Hormone produced by the ovaries during pregnancy that loosens ligaments that hold the hip bones together. [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] Renal Replacement Therapy: Procedures which temporarily or permanently remedy insufficient cleansing of body fluids by the kidneys. [NIH] Renin: An enzyme which is secreted by the kidney and is formed from prorenin in plasma and kidney. The enzyme cleaves the Leu-Leu bond in angiotensinogen to generate angiotensin I. EC 3.4.23.15. (Formerly EC 3.4.99.19). [NIH] Renin-Angiotensin System: A system consisting of renin, angiotensin-converting enzyme, and angiotensin II. Renin, an enzyme produced in the kidney, acts on angiotensinogen, an alpha-2 globulin produced by the liver, forming angiotensin I. The converting enzyme contained in the lung acts on angiotensin I in the plasma converting it to angiotensin II, the most powerful directly pressor substance known. It causes contraction of the arteriolar smooth muscle and has other indirect actions mediated through the adrenal cortex. [NIH] Reperfusion: Restoration of blood supply to tissue which is ischemic due to decrease in normal blood supply. The decrease may result from any source including atherosclerotic obstruction, narrowing of the artery, or surgical clamping. It is primarily a procedure for treating infarction or other ischemia, by enabling viable ischemic tissue to recover, thus limiting further necrosis. However, it is thought that reperfusion can itself further damage the ischemic tissue, causing reperfusion injury. [NIH] Reperfusion Injury: Functional, metabolic, or structural changes, including necrosis, in ischemic tissues thought to result from reperfusion to ischemic areas of the tissue. The most common instance is myocardial reperfusion injury. [NIH] Reproduction Techniques: Methods pertaining to the generation of new individuals. [NIH] Reproductive system: In women, this system includes the ovaries, the fallopian tubes, the uterus (womb), the cervix, and the vagina (birth canal). The reproductive system in men includes the prostate, the testes, and the penis. [NIH] Research Design: A plan for collecting and utilizing data so that desired information can be obtained with sufficient precision or so that an hypothesis can be tested properly. [NIH] Resected: Surgical removal of part of an organ. [NIH] Resection: Removal of tissue or part or all of an organ by surgery. [NIH] Residual disease: Cancer cells that remain after attempts have been made to remove the cancer. [NIH] Resorption: The loss of substance through physiologic or pathologic means, such as loss of

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dentin and cementum of a tooth, or of the alveolar process of the mandible or maxilla. [EU] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Respiratory distress syndrome: A lung disease that occurs primarily in premature infants; the newborn must struggle for each breath and blueing of its skin reflects the baby's inability to get enough oxygen. [NIH] Response rate: The percentage of patients whose cancer shrinks or disappears after treatment. [NIH] Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [NIH] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] Retinae: A congenital notch or cleft of the retina, usually located inferiorly. [NIH] Retinoid: Vitamin A or a vitamin A-like compound. [NIH] Retroperitoneal: Having to do with the area outside or behind the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Retropubic: A potential space between the urinary bladder and the symphisis and body of the pubis. [NIH] Retropubic prostatectomy: Surgery to remove the prostate through an incision made in the abdominal wall. [NIH] Retrospective: Looking back at events that have already taken place. [NIH] Retrospective Studies: Studies used to test etiologic hypotheses in which inferences about an exposure to putative causal factors are derived from data relating to characteristics of persons under study or to events or experiences in their past. The essential feature is that some of the persons under study have the disease or outcome of interest and their characteristics are compared with those of unaffected persons. [NIH] Retrospective study: A study that looks backward in time, usually using medical records and interviews with patients who already have or had a disease. [NIH] Reversion: A return to the original condition, e. g. the reappearance of the normal or wild type in previously mutated cells, tissues, or organisms. [NIH] Rheumatic Diseases: Disorders of connective tissue, especially the joints and related structures, characterized by inflammation, degeneration, or metabolic derangement. [NIH] Rheumatism: A group of disorders marked by inflammation or pain in the connective tissue structures of the body. These structures include bone, cartilage, and fat. [NIH] Rheumatoid: Resembling rheumatism. [EU] Rheumatoid arthritis: A form of arthritis, the cause of which is unknown, although infection, hypersensitivity, hormone imbalance and psychologic stress have been suggested as possible causes. [NIH] Ribonucleic acid: RNA. One of the two nucleic acids found in all cells. The other is deoxyribonucleic acid (DNA). Ribonucleic acid transfers genetic information from DNA to proteins produced by the cell. [NIH]

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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] Rod: A reception for vision, located in the retina. [NIH] Saliva: The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptylin. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Saphenous: Applied to certain structures in the leg, e. g. nerve vein. [NIH] Saphenous Vein: The vein which drains the foot and leg. [NIH] Saponins: Sapogenin glycosides. A type of glycoside widely distributed in plants. Each consists of a sapogenin as the aglycon moiety, and a sugar. The sapogenin may be a steroid or a triterpene and the sugar may be glucose, galactose, a pentose, or a methylpentose. Sapogenins are poisonous towards the lower forms of life and are powerful hemolytics when injected into the blood stream able to dissolve red blood cells at even extreme dilutions. [NIH] 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] Schizoid: Having qualities resembling those found in greater degree in schizophrenics; a person of schizoid personality. [NIH] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [NIH] Schizotypal Personality Disorder: A personality disorder in which there are oddities of thought (magical thinking, paranoid ideation, suspiciousness), perception (illusions, depersonalization), speech (digressive, vague, overelaborate), and behavior (inappropriate affect in social interactions, frequently social isolation) that are not severe enough to characterize schizophrenia. [NIH] Sclerae: A circular furrow between the sclerocorneal junction and the iris. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Scrotum: In males, the external sac that contains the testicles. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Secretory: Secreting; relating to or influencing secretion or the secretions. [NIH] Sedative: 1. Allaying activity and excitement. 2. An agent that allays excitement. [EU] Sedentary: 1. Sitting habitually; of inactive habits. 2. Pertaining to a sitting posture. [EU] Segregation: The separation in meiotic cell division of homologous chromosome pairs and

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their contained allelomorphic gene pairs. [NIH] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH] Selective estrogen receptor modulator: SERM. A drug that acts like estrogen on some tissues, but blocks the effect of estrogen on other tissues. Tamoxifen and raloxifene are SERMs. [NIH] Sella: A deep depression in the shape of a Turkish saddle in the upper surface of the body of the sphenoid bone in the deepest part of which is lodged the hypophysis cerebri. [NIH] Semen: The thick, yellowish-white, viscid fluid secretion of male reproductive organs discharged upon ejaculation. In addition to reproductive organ secretions, it contains spermatozoa and their nutrient plasma. [NIH] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [NIH] Sepsis: The presence of bacteria in the bloodstream. [NIH] 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] Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (receptors, serotonin) explain the broad physiological actions and distribution of this biochemical mediator. [NIH] Serous: Having to do with serum, the clear liquid part of blood. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Sex Characteristics: Those characteristics that distinguish one sex from the other. The primary sex characteristics are the ovaries and testes and their related hormones. Secondary sex characteristics are those which are masculine or feminine but not directly related to reproduction. [NIH] Sex Hormone-Binding Globulin: A glycoprotein migrating as a beta-globulin. Its molecular weight, 52,000 or 95,000-115,000, indicates that it exists as a dimer. The protein binds testosterone, dihydrotestosterone, and estradiol in the plasma. Sex hormone-binding protein has the same amino acid sequence as androgen-binding protein. They differ by their sites of synthesis and post-translational oligosacaccharide modifications. [NIH] Sexually Transmitted Diseases: Diseases due to or propagated by sexual contact. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]

Short Bowel Syndrome: A malabsorption syndrome resulting from extensive operative resection of small bowel. [NIH]

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Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Skin graft: Skin that is moved from one part of the body to another. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Sleep apnea: A serious, potentially life-threatening breathing disorder characterized by repeated cessation of breathing due to either collapse of the upper airway during sleep or absence of respiratory effort. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]

Smooth Muscle Tumor: A tumor composed of smooth muscle tissue, as opposed to leiomyoma, a tumor derived from smooth muscle. [NIH] Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Social Work: The use of community resources, individual case work, or group work to promote the adaptive capacities of individuals in relation to their social and economic environments. It includes social service agencies. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by

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refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Sperm: The fecundating fluid of the male. [NIH] Sperm Maturation: Posttesticular ripening of spermatozoa. [NIH] Spermatids: Male germ cells derived from spermatocytes and developing into spermatozoa. [NIH]

Spermatocytes: Male germ cells derived from spermatogonia and developing into spermatids. [NIH] Spermatogenesis: Process of formation and development of spermatozoa, including spermatocytogenesis and spermiogenesis. [NIH] Spermatogonia: The spermatocytes. [NIH]

primitive

differentiated

male

gametes

which

give

rise

to

Spermatozoa: Mature male germ cells that develop in the seminiferous tubules of the testes. Each consists of a head, a body, and a tail that provides propulsion. The head consists mainly of chromatin. [NIH] Sphenoid: An unpaired cranial bone with a body containing the sphenoid sinus and forming the posterior part of the medial walls of the orbits. [NIH] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spleen: An organ that is part of the lymphatic system. The spleen produces lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side of the abdomen near the stomach. [NIH] Spontaneous Abortion: The non-induced birth of an embryo or of fetus prior to the stage of viability at about 20 weeks of gestation. [NIH] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [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]

Steel: A tough, malleable, iron-based alloy containing up to, but no more than, two percent carbon and often other metals. It is used in medicine and dentistry in implants and instrumentation. [NIH] Stem cell transplantation: A method of replacing immature blood-forming cells that were destroyed by cancer treatment. The stem cells are given to the person after treatment to help the bone marrow recover and continue producing healthy blood cells. [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] Stents: Devices that provide support for tubular structures that are being anastomosed or for body cavities during skin grafting. [NIH] Sterile: Unable to produce children. [NIH] Sterility: 1. The inability to produce offspring, i.e., the inability to conceive (female s.) or to induce conception (male s.). 2. The state of being aseptic, or free from microorganisms. [EU] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this

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group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Steroid therapy: Treatment with corticosteroid drugs to reduce swelling, pain, and other symptoms of inflammation. [NIH] Stillbirth: The birth of a dead fetus or baby. [NIH] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]

Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] 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] Stricture: The abnormal narrowing of a body opening. Also called stenosis. [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] Stromal: Large, veil-like cell in the bone marrow. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subarachnoid: Situated or occurring between the arachnoid and the pia mater. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subcutaneous: Beneath the skin. [NIH] Sublingual: Located beneath the tongue. [EU] 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] Superovulation: Occurrence or induction of release of more ova than are normally released at the same time in a given species. The term applies to both animals and humans. [NIH] Supplementation: Adding nutrients to the diet. [NIH] Support group: A group of people with similar disease who meet to discuss how better to cope with their cancer and treatment. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Suprachiasmatic Nucleus: An ovoid densely packed collection of small cells of the anterior hypothalamus lying close to the midline in a shallow impression of the optic chiasm. [NIH] Surfactant: A fat-containing protein in the respiratory passages which reduces the surface tension of pulmonary fluids and contributes to the elastic properties of pulmonary tissue. [NIH]

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Survival Rate: The proportion of survivors in a group, e.g., of patients, studied and followed over a period, or the proportion of persons in a specified group alive at the beginning of a time interval who survive to the end of the interval. It is often studied using life table methods. [NIH] Symphysis: A secondary cartilaginous joint. [NIH] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Synapses: Specialized junctions at which a neuron communicates with a target cell. At classical synapses, a neuron's presynaptic terminal releases a chemical transmitter stored in synaptic vesicles which diffuses across a narrow synaptic cleft and activates receptors on the postsynaptic membrane of the target cell. The target may be a dendrite, cell body, or axon of another neuron, or a specialized region of a muscle or secretory cell. Neurons may also communicate through direct electrical connections which are sometimes called electrical synapses; these are not included here but rather in gap junctions. [NIH] Synapsis: The pairing between homologous chromosomes of maternal and paternal origin during the prophase of meiosis, leading to the formation of gametes. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Synaptic Vesicles: Membrane-bound compartments which contain transmitter molecules. Synaptic vesicles are concentrated at presynaptic terminals. They actively sequester transmitter molecules from the cytoplasm. In at least some synapses, transmitter release occurs by fusion of these vesicles with the presynaptic membrane, followed by exocytosis of their contents. [NIH] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Systemic: Affecting the entire body. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Tamoxifen: A first generation selective estrogen receptor modulator (SERM). It acts as an agonist for bone tissue and cholesterol metabolism but is an estrogen antagonist in mammary and uterine. [NIH] Technetium: The first artificially produced element and a radioactive fission product of uranium. The stablest isotope has a mass number 99 and is used diagnostically as a radioactive imaging agent. Technetium has the atomic symbol Tc, atomic number 43, and atomic weight 98.91. [NIH] Telomerase: Essential ribonucleoprotein reverse transcriptase that adds telomeric DNA to the ends of eukaryotic chromosomes. Telomerase appears to be repressed in normal human somatic tissues but reactivated in cancer, and thus may be necessary for malignant transformation. EC 2.7.7.-. [NIH] 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] Teratogens: An agent that causes the production of physical defects in the developing embryo. [NIH] Testicles: The two egg-shaped glands found inside the scrotum. They produce sperm and male hormones. Also called testes. [NIH]

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Testicular: Pertaining to a testis. [EU] Testis: Either of the paired male reproductive glands that produce the male germ cells and the male hormones. [NIH] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] Tetany: 1. Hyperexcitability of nerves and muscles due to decrease in concentration of extracellular ionized calcium, which may be associated with such conditions as parathyroid hypofunction, vitamin D deficiency, and alkalosis or result from ingestion of alkaline salts; it is characterized by carpopedal spasm, muscular twitching and cramps, laryngospasm with inspiratory stridor, hyperreflexia and choreiform movements. 2. Tetanus. [EU] Tetracycline: An antibiotic originally produced by Streptomyces viridifaciens, but used mostly in synthetic form. It is an inhibitor of aminoacyl-tRNA binding during protein synthesis. [NIH] Thalassemia: A group of hereditary hemolytic anemias in which there is decreased synthesis of one or more hemoglobin polypeptide chains. There are several genetic types with clinical pictures ranging from barely detectable hematologic abnormality to severe and fatal anemia. [NIH] Thalidomide: A pharmaceutical agent originally introduced as a non-barbiturate hypnotic, but withdrawn from the market because of its known tetratogenic effects. It has been reintroduced and used for a number of immunological and inflammatory disorders. Thalidomide displays immunosuppresive and anti-angiogenic activity. It inhibits release of tumor necrosis factor alpha from monocytes, and modulates other cytokine action. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thigh: A leg; in anatomy, any elongated process or part of a structure more or less comparable to a leg. [NIH] Third Ventricle: A narrow cleft inferior to the corpus callosum, within the diencephalon, between the paired thalami. Its floor is formed by the hypothalamus, its anterior wall by the lamina terminalis, and its roof by ependyma. It communicates with the fourth ventricle by the cerebral aqueduct, and with the lateral ventricles by the interventricular foramina. [NIH] Thorax: A part of the trunk between the neck and the abdomen; the chest. [NIH] Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombocytes: Blood cells that help prevent bleeding by causing blood clots to form. Also called platelets. [NIH] Thromboembolism: Obstruction of a vessel by a blood clot that has been transported from a distant site by the blood stream. [NIH] Thrombolytic: 1. Dissolving or splitting up a thrombus. 2. A thrombolytic agent. [EU] Thrombophilia: A disorder of hemostasis in which there is a tendency for the occurrence of thrombosis. [NIH] Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH]

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Thrombus: An aggregation of blood factors, primarily platelets and fibrin with entrapment of cellular elements, frequently causing vascular obstruction at the point of its formation. Some authorities thus differentiate thrombus formation from simple coagulation or clot formation. [EU] Thymus: An organ that is part of the lymphatic system, in which T lymphocytes grow and multiply. The thymus is in the chest behind the breastbone. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Thyroid Gland: A highly vascular endocrine gland consisting of two lobes, one on either side of the trachea, joined by a narrow isthmus; it produces the thyroid hormones which are concerned in regulating the metabolic rate of the body. [NIH] Thyroid Hormones: Hormones secreted by the thyroid gland. [NIH] Thyrotropin: A peptide hormone secreted by the anterior pituitary. It promotes the growth of the thyroid gland and stimulates the synthesis of thyroid hormones and the release of thyroxine by the thyroid gland. [NIH] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH] Tin: A trace element that is required in bone formation. It has the atomic symbol Sn, atomic number 50, and atomic weight 118.71. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tissue Transplantation: Transference of tissue within an individual, between individuals of the same species, or between individuals of different species. [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] Total androgen blockade: Therapy used to eliminate male sex hormones (androgens) in the body. This may be done with surgery, hormonal therapy, or a combination. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicokinetics: Study of the absorption, distribution, metabolism, and excretion of test substances. [NIH] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific

Dictionary 257

biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [NIH] Trace element: Substance or element essential to plant or animal life, but present in extremely small amounts. [NIH] Tracer: A substance (such as a radioisotope) used in imaging procedures. [NIH] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Traction: The act of pulling. [NIH] Tragacanth: Powdered exudate from Astragalus gummifer and related plants. It forms gelatinous mass in water. Tragacanth is used as suspending agent, excipient or emulsifier in foods, cosmetics and pharmaceuticals. It has also been used as a bulk-forming laxative. [NIH] Transcriptase: An enzyme which catalyses the synthesis of a complementary mRNA molecule from a DNA template in the presence of a mixture of the four ribonucleotides (ATP, UTP, GTP and CTP). [NIH] Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. [NIH] Transdermal: Entering through the dermis, or skin, as in administration of a drug applied to the skin in ointment or patch form. [EU] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] 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] Transurethral: Performed through the urethra. [EU] Transurethral Resection of Prostate: Resection of the prostate using a cystoscope passed through the urethra. [NIH] Trastuzumab: A type of monoclonal antibody used in cancer detection or therapy. Monoclonal antibodies are laboratory-produced substances that can locate and bind to cancer cells. Trastuzumab blocks the effects of the growth factor protein HER2, which transmits growth signals to breast cancer cells. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Treatment Failure: A measure of the quality of health care by assessment of unsuccessful results of management and procedures used in combating disease, in individual cases or series. [NIH] Triad: Trivalent. [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]

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Triptorelin: A long-acting gonadorelin analog agonist. It has been used in the treatment of prostatic cancer, ovarian cancer, precocious puberty, endometriosis, and to induce ovulation for in vitro fertilization. [NIH] Trophoblast: The outer layer of cells of the blastocyst which works its way into the endometrium during ovum implantation and grows rapidly, later combining with mesoderm. [NIH] Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Tuberculosis: Any of the infectious diseases of man and other animals caused by species of Mycobacterium. [NIH] Tumor marker: A substance sometimes found in an increased amount in the blood, other body fluids, or tissues and which may mean that a certain type of cancer is in the body. Examples of tumor markers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and gastrointestinal tract cancers), and PSA (prostate cancer). Also called biomarker. [NIH] Tumor 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] Tumor Necrosis Factor: Serum glycoprotein produced by activated macrophages and other mammalian mononuclear leukocytes which has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. It mimics the action of endotoxin but differs from it. It has a molecular weight of less than 70,000 kDa. [NIH] Tumor-derived: Taken from an individual's own tumor tissue; may be used in the development of a vaccine that enhances the body's ability to build an immune response to the tumor. [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] Ultrasonography: The visualization of deep structures of the body by recording the reflections of echoes of pulses of ultrasonic waves directed into the tissues. Use of ultrasound for imaging or diagnostic purposes employs frequencies ranging from 1.6 to 10 megahertz. [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Uranium: A radioactive element of the actinide series of metals. It has an atomic symbol U, atomic number 92, and atomic weight 238.03. U-235 is used as the fissionable fuel in nuclear weapons and as fuel in nuclear power reactors. [NIH] Urea: A compound (CO(NH2)2), formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids. [NIH] Uremia: The illness associated with the buildup of urea in the blood because the kidneys are not working effectively. Symptoms include nausea, vomiting, loss of appetite, weakness, and mental confusion. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]

Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urinary tract: The organs of the body that produce and discharge urine. These include the

Dictionary 259

kidneys, ureters, bladder, and urethra. [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] Urologist: A doctor who specializes in diseases of the urinary organs in females and the urinary and sex organs in males. [NIH] Urology: A surgical specialty concerned with the study, diagnosis, and treatment of diseases of the urinary tract in both sexes and the genital tract in the male. It includes the specialty of andrology which addresses both male genital diseases and male infertility. [NIH] Uterus: The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called the womb. [NIH] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Vaginal: Of or having to do with the vagina, the birth canal. [NIH] Valves: Flap-like structures that control the direction of blood flow through the heart. [NIH] Varices: Stretched veins such as those that form in the esophagus from cirrhosis. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] 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] Vasectomy: An operation to cut or tie off the two tubes that carry sperm out of the testicles. [NIH]

Vasodilator: An agent that widens blood vessels. [NIH] Vasomotor: 1. Affecting the calibre of a vessel, especially of a blood vessel. 2. Any element or agent that effects the calibre of a blood vessel. [EU] Vasopressor: 1. Stimulating contraction of the muscular tissue of the capillaries and arteries. 2. An agent that stimulates contraction of the muscular tissue of the capillaries and arteries. [EU]

Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venous: Of or pertaining to the veins. [EU] Venous blood: Blood that has given up its oxygen to the tissues and carries carbon dioxide back for gas exchange. [NIH] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Ventricular: Pertaining to a ventricle. [EU] Ventricular Function: The hemodynamic and electrophysiological action of the ventricles. [NIH]

Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Vertebrae: A bony unit of the segmented spinal column. [NIH] Vertebral: Of or pertaining to a vertebra. [EU] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and

260 Hormone Therapy

treatment of diseases in animals. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Viral Load: The quantity of measurable virus in the blood. Change in viral load, measured in plasma, is used as a surrogate marker in HIV disease progression. [NIH] Virilism: Development of masculine traits in the female. [NIH] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] Visceral fat: One of the three compartments of abdominal fat. Retroperitoneal and subcutaneous are the other two compartments. [NIH] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] Waist circumference: To define the level at which the waist circumference is measured, a bony landmark is first located and marked. The subject stands, and the technician, positioned to the right of the subject, palpates the upper hip bone to locate the right ileum. Just above the uppermost lateral border of the right ileum, a horizontal mark is drawn and then crossed with a vertical mark on the midaxillary line. The measuring tape is then placed around the trunk, at the level of the mark on the right side, making sure that it is on a level horizontal plane on all sides. The tape is then tightened slightly without compressing the skin and underlying subcutaneous tissues. The measure is recorded in centimeters to the nearest millimeter. [NIH] Watchful waiting: Closely monitoring a patient's condition but withholding treatment until symptoms appear or change. Also called observation. [NIH] Weight Gain: Increase in body weight over existing weight. [NIH] Weight-Bearing: The physical state of supporting an applied load. This often refers to the weight-bearing bones or joints that support the body's weight, especially those in the spine, hip, knee, and foot. [NIH] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]

Windpipe: A rigid tube, 10 cm long, extending from the cricoid cartilage to the upper border of the fifth thoracic vertebra. [NIH] Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) A substance-specific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU] Womb: A hollow, thick-walled, muscular organ in which the impregnated ovum is developed into a child. [NIH] Xenograft: The cells of one species transplanted to another species. [NIH]

Dictionary 261

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]

263

INDEX A Abdomen, 187, 195, 205, 224, 225, 226, 238, 248, 252, 253, 255 Abdominal, 29, 30, 47, 53, 187, 215, 225, 228, 236, 238, 248, 260 Abdominal fat, 47, 53, 187, 260 Aberrant, 7, 187 Ablation, 7, 39, 60, 89, 187, 190 Acceptor, 187, 226, 235 Acetylcholine, 187, 199, 233 Acidosis, 9, 187 Acne, 149, 187, 205 Acute lymphoblastic leukemia, 127, 187 Acute lymphocytic leukemia, 127, 187 Adaptation, 26, 55, 94, 187 Adenoma, 79, 187 Adenosine, 187, 193, 196, 239 Adipocytes, 187, 226 Adipose Tissue, 14, 73, 187, 188, 246 Adjustment, 187, 188 Adjuvant, 39, 41, 45, 63, 68, 84, 87, 128, 188 Adjuvant Therapy, 41, 188 Adrenal Cortex, 188, 190, 204, 212, 219, 220, 242, 247 Adrenal Glands, 115, 116, 118, 119, 120, 122, 188 Adrenal insufficiency, 33, 188 Adverse Effect, 13, 17, 26, 44, 50, 188, 251 Aerobic, 18, 33, 148, 188, 213 Aerobic Exercise, 18, 33, 188 Afferent, 188, 226 Affinity, 21, 53, 142, 188, 251 Agonist, 11, 17, 69, 188, 200, 208, 217, 232, 246, 254, 258 Airway, 188, 251 Alanine, 188, 231 Alendronate, 37, 70, 71, 188 Alertness, 188, 196 Algorithms, 189, 194 Alimentary, 189, 211, 236 Alkaline, 187, 189, 196, 255 Alkaloid, 189, 201 Alleles, 20, 189 Allogeneic, 189, 238 Allograft, 66, 82, 189 Alpha Particles, 189, 245 Alternative medicine, 158, 189 Alveolar Bone Loss, 37, 189

Amenorrhea, 90, 109, 156, 159, 189, 241 Amino Acid Sequence, 189, 190, 191, 213, 250 Amino Acids, 189, 190, 213, 237, 241, 244, 249, 250, 257, 258 Ammonia, 189, 217, 258 Amnion, 189 Amniotic Fluid, 151, 189, 216 Amphetamines, 189, 201 Amplification, 45, 79, 189 Anabolic, 12, 36, 43, 99, 144, 189, 207 Anaerobic, 25, 190 Anaesthesia, 190, 222 Anal, 45, 190, 214, 227 Analog, 57, 74, 190, 196, 226, 232, 258 Analogous, 190, 209, 257 Anaphylatoxins, 190, 202 Anaplasia, 190, 232, 243 Anatomical, 190, 222 Androgen suppression, 114, 117, 119, 126, 190 Androgen-Binding Protein, 190, 250 Androgenic, 12, 142, 144, 190 Androstenedione, 44, 190 Anemia, 190, 194, 214, 255 Angina, 71, 190 Angiogram, 142, 190 Angioplasty, 71, 190, 231 Angiotensinogen, 6, 190, 247 Animal model, 11, 190, 258 Anovulation, 12, 44, 191, 241 Antagonism, 56, 191, 196 Antiandrogen therapy, 60, 191 Antiandrogens, 191, 194, 233 Antibacterial, 191, 252 Antibiotic, 191, 237, 252, 255 Antibodies, 45, 54, 58, 96, 104, 111, 191, 218, 219, 221, 227, 231, 240, 245 Antibody, 45, 58, 121, 129, 188, 191, 201, 218, 219, 221, 222, 224, 228, 231, 245, 251, 257, 261 Antibody therapy, 121, 129, 191 Anticoagulant, 58, 191, 243 Antidepressant, 12, 191 Antidiabetic, 13, 191 Antiepileptic, 52, 191 Antifungal, 191, 225

264 Hormone Therapy

Antigen, 24, 57, 88, 94, 188, 191, 202, 219, 220, 222, 228 Antigen-Antibody Complex, 191, 202 Antihypertensive, 18, 191 Anti-infective, 191, 224 Anti-inflammatory, 55, 131, 191, 192, 204, 207, 216, 236, 242 Anti-Inflammatory Agents, 191, 192, 204 Antineoplastic, 192, 197, 204, 205, 216, 230, 236 Antioxidant, 34, 84, 192, 236 Antiproliferative, 79, 192 Antiseptic, 192, 197 Antiviral, 192, 237 Anuria, 192, 225 Anus, 190, 192, 195, 246 Anxiety, 34, 192 Aorta, 53, 192, 204, 218, 242, 259 Apnea, 38, 192 Apolipoproteins, 4, 192, 226 Apoptosis, 43, 56, 192, 213 Applicability, 140, 192 Aqueous, 192, 193, 206, 210 Arginine, 131, 132, 140, 190, 192, 233 Arsenic trioxide, 113, 192 Arterial, 33, 46, 84, 85, 192, 199, 220, 244, 254 Arteries, 5, 31, 130, 141, 192, 193, 195, 196, 204, 218, 224, 227, 230, 231, 259 Arteriolar, 192, 196, 247 Arterioles, 192, 195, 231, 259 Articular, 192, 235 Ascites, 192, 235 Aspirin, 14, 49, 192 Assay, 18, 137, 192 Astringent, 192, 197 Asymptomatic, 60, 100, 139, 193, 194 Atherogenic, 47, 193 ATP, 28, 193, 208, 216, 239, 244, 257 Atrophy, 68, 141, 143, 193 Attenuated, 19, 193, 207 Autoimmune disease, 193 Autoimmunity, 58, 193 Autologous, 193, 238 Autonomic, 33, 187, 193, 238 Axillary, 45, 193, 196, 230 Axillary Artery, 193, 196 B Bacteria, 191, 193, 203, 206, 211, 219, 230, 240, 250, 252, 259 Bacterial Physiology, 187, 193 Balloon Dilatation, 148, 193

Balloon dilation, 170, 193 Barbiturate, 193, 255 Baroreflex, 33, 193 Base, 31, 42, 99, 104, 136, 193, 206, 225, 254 Benign, 42, 138, 170, 187, 193, 194, 214, 218, 226, 232, 245 Benign prostatic hyperplasia, 170, 193, 214 Benign tumor, 194, 226 Beta-Thalassemia, 99, 194 Bewilderment, 194, 202 Bicalutamide, 115, 118, 119, 120, 122, 124, 194 Bilateral, 15, 121, 194, 241 Bile, 194, 215, 226, 253 Biliary, 193, 194, 197 Bioavailability, 13, 21, 194 Bioavailable, 21, 23, 194 Biochemical, 11, 32, 86, 88, 137, 189, 194, 225, 250 Biological therapy, 114, 194, 218, 228 Biomarkers, 34, 194 Biopsy, 170, 194, 237 Biosynthesis, 23, 194, 212, 235, 250 Biotechnology, 62, 150, 158, 169, 194 Biotransformation, 13, 194 Bladder, 193, 194, 195, 222, 243, 248, 258, 259 Blast phase, 195, 200 Blastocyst, 45, 195, 202, 210, 239, 258 Blood Coagulation, 195, 196 Blood Platelets, 49, 195, 250 Blood pressure, 18, 33, 50, 85, 191, 193, 195, 197, 220, 231, 251 Blot, 45, 195 Body Composition, 7, 13, 15, 24, 29, 30, 35, 38, 48, 62, 63, 67, 68, 86, 195 Body Fluids, 194, 195, 196, 209, 247, 251, 258 Body Mass Index, 195, 213 Bone Density, 22, 36, 43, 50, 62, 195 Bone Development, 148, 195 Bone Marrow, 84, 187, 195, 200, 205, 221, 227, 238, 252, 253 Bone Resorption, 37, 195, 196 Bone scan, 195, 249 Bowel, 3, 26, 31, 128, 190, 195, 207, 224, 225, 238, 250, 253 Bowel Movement, 195, 207, 253 Brachial, 18, 195, 196, 245 Brachial Artery, 18, 196, 245 Brachytherapy, 196, 223, 224, 245, 261 Bradykinin, 196, 233, 240

Index 265

Branch, 183, 196, 210, 216, 227, 237, 244, 251, 255 Breakdown, 11, 196, 207, 215 Bromine, 53, 196 Bronchial, 193, 196 Buccal, 196, 227 Buffers, 193, 196 Buserelin, 116, 196 Bypass, 48, 55, 196, 231 C Caffeine, 14, 196 Calcifediol, 196 Calcitriol, 23, 57, 123, 196 Calcium, 35, 36, 50, 65, 196, 201, 220, 231, 236, 244, 255 Calculi, 193, 197 Caloric intake, 159, 197 Capsules, 136, 197, 209 Carbohydrate, 26, 65, 86, 197, 204, 216, 241 Carbon Dioxide, 197, 214, 215, 239, 248, 259 Carboplatin, 23, 122, 131, 197 Carcinogen, 197, 212 Carcinogenesis, 8, 197 Carcinogenic, 8, 197, 223, 243, 253 Carcinoma, 45, 82, 89, 137, 197, 205 Cardiac, 18, 19, 25, 32, 48, 65, 82, 100, 193, 196, 197, 204, 212, 231, 233, 236, 253 Cardiac Output, 193, 197 Cardiology, 18, 32, 68, 71, 82, 92, 197 Cardiomyopathy, 19, 25, 197 Cardiorespiratory, 188, 197 Cardiovascular disease, 14, 29, 32, 46, 47, 58, 62, 66, 89, 91, 92, 96, 140, 197, 226 Cardiovascular System, 32, 81, 197 Case report, 33, 67, 83, 85, 104, 197, 200 Case series, 17, 197, 200 Catabolism, 64, 197 Catechol, 8, 197 Catheterization, 32, 190, 193, 198, 224, 231 Catheters, 148, 193, 198, 222, 223 Caudal, 198, 207, 221, 241 Causal, 15, 38, 55, 60, 198, 248 Cause of Death, 48, 198 Cell Cycle, 41, 55, 198, 200, 205, 244 Cell Cycle Proteins, 55, 198 Cell Death, 192, 198, 213, 232 Cell Differentiation, 44, 198 Cell Division, 141, 193, 198, 218, 229, 230, 239, 243, 249 Cell proliferation, 26, 45, 55, 198 Cell Respiration, 198, 248

Cell Survival, 198, 218 Cell Transplantation, 121, 198 Cellobiose, 198 Cellulose, 140, 198, 239 Central Nervous System Infections, 198, 218 Cerebral, 9, 28, 199, 203, 212, 255 Cerebrovascular, 9, 197, 199 Cerebrum, 199, 239 Cervical, 11, 144, 199 Cervical Ripening, 11, 199 Cervix, 11, 199, 247 Character, 199, 206 Chemotactic Factors, 199, 202 Chlormadinone Acetate, 69, 199 Cholesterol Esters, 199, 226 Cholinergic, 9, 41, 72, 199 Chromaffin System, 199, 211 Chromatin, 192, 198, 199, 252 Chromosomal, 189, 199, 234, 240 Chromosome, 199, 203, 215, 218, 226, 249 Chronic Disease, 13, 14, 151, 199, 201 Chronic lymphocytic leukemia, 199, 200 Chronic myelogenous leukemia, 195, 200 Chronic phase, 33, 200 Chronic renal, 36, 68, 70, 77, 138, 200, 240 Chylomicrons, 200, 226 Circadian, 54, 200 Circulatory system, 200, 210 CIS, 36, 200 Cisplatin, 23, 200 Clamp, 18, 30, 200 Clear cell carcinoma, 200, 207 Climacteric, 60, 85, 200 Clinical study, 200, 203 Clomiphene, 12, 200 Cloning, 194, 200 Coagulation, 30, 38, 48, 195, 200, 219, 225, 240, 256 Coca, 201 Cocaine, 25, 201 Cofactor, 201, 244 Cognition, 5, 40, 59, 201 Collagen, 11, 201, 214, 220, 235, 240, 243 Collagen disease, 201, 220 Collapse, 196, 201, 251 Colorectal, 31, 201 Colorectal Cancer, 31, 201 Combination chemotherapy, 114, 115, 117, 120, 124, 125, 201 Combination Therapy, 43, 125, 201, 212 Complement, 41, 51, 190, 201, 202, 240

266 Hormone Therapy

Complementary and alternative medicine, 107, 109, 202 Complementary medicine, 107, 202 Complete remission, 202, 247 Computational Biology, 169, 202 Computed tomography, 41, 48, 195, 202, 249 Computerized axial tomography, 202, 249 Computerized tomography, 29, 202 Conception, 202, 203, 214, 228, 242, 252 Concomitant, 16, 202 Condoms, 145, 202 Confounding, 9, 13, 45, 202 Confusion, 83, 202, 208, 258 Conjugated, 8, 29, 59, 162, 203, 205 Conjugation, 194, 203 Connective Tissue, 195, 201, 203, 215, 227, 233, 248 Consciousness, 203, 206, 208 Constriction, 203, 224 Consumption, 13, 15, 203, 215, 234, 236 Continuum, 38, 203 Contraception, 138, 144, 203 Contraceptive, 11, 39, 42, 58, 69, 137, 138, 142, 144, 157, 199, 203, 210, 229 Contraindications, ii, 203 Control group, 4, 57, 60, 203, 242, 246 Controlled clinical trial, 12, 203 Controlled study, 18, 50, 51, 203 Contusions, 15, 203 Conventional therapy, 25, 37, 203 Conventional treatment, 203 Convulsions, 193, 203, 233 Coordination, 41, 203 Coronary, 18, 19, 31, 37, 48, 49, 53, 68, 69, 71, 81, 91, 97, 101, 108, 131, 141, 197, 203, 204, 230, 231 Coronary Artery Bypass, 48, 204 Coronary Circulation, 132, 204 Coronary Disease, 37, 48, 204 Coronary heart disease, 18, 19, 49, 69, 71, 91, 131, 197, 204 Coronary Thrombosis, 204, 230, 231 Coronary Vessels, 49, 204 Corpus, 204, 227, 237, 239, 242, 255 Corpus Luteum, 204, 227, 242 Cortex, 144, 204, 212 Cortical, 15, 29, 35, 43, 101, 108, 204, 213, 250 Corticosteroid, 204, 242, 253 Cortisol, 12, 33, 204 Cortisone, 204, 207, 242

Cranial, 99, 104, 204, 218, 238, 252 Craniocerebral Trauma, 204, 218 Creatine, 39, 204 Creatinine, 205, 225 Crossing-over, 205, 246 Cryptorchidism, 54, 205, 233 Curative, 205, 255 Cutaneous, 205, 227 Cyclic, 14, 16, 44, 51, 67, 196, 205, 218, 233 Cyclin, 55, 198, 205 Cyclin-Dependent Kinases, 198, 205 Cyclophosphamide, 205, 221 Cyclosporine, 66, 205 Cyproterone, 120, 205, 214 Cyst, 139, 205, 235 Cytochrome, 8, 205 Cytokine, 20, 205, 223, 255 Cytomegalovirus, 130, 205 Cytoplasm, 192, 206, 211, 217, 249, 254 Cytoskeletal Proteins, 198, 206 Cytotoxic, 206, 245 Cytotoxicity, 200, 206 D Data Collection, 35, 206 Databases, Bibliographic, 169, 206 Degenerative, 13, 206 Dehydroepiandrosterone, 13, 141, 206 Deja Vu, 81, 206 Deletion, 10, 54, 192, 206 Dementia, 20, 28, 58, 206 Dendrites, 206, 233 Density, 4, 13, 19, 22, 35, 36, 41, 50, 59, 61, 66, 70, 86, 91, 96, 100, 104, 195, 206, 209, 226, 234, 241 Dental Care, 148, 206 Dental Caries, 206, 214 Deoxyribonucleic, 206, 248 Deoxyribonucleic acid, 206, 248 Deprivation, 22, 43, 55, 207 DES, 120, 190, 207 Deuterium, 48, 207, 220 Dexamethasone, 23, 123, 128, 207 Diabetes Mellitus, 14, 75, 150, 151, 207, 216, 218 Diagnostic Imaging, 52, 207 Diagnostic procedure, 135, 158, 207 Dialyzer, 207, 218 Diastolic, 207, 220 Diencephalon, 207, 221, 255 Diffusion, 207 Digestion, 189, 194, 195, 207, 224, 226, 236, 253

Index 267

Digestive system, 133, 207 Digestive tract, 207, 251 Digital rectal examination, 170, 207 Dihydrotestosterone, 21, 144, 207, 246, 250 Dilatation, 18, 190, 207, 242 Dilated cardiomyopathy, 25, 100, 207 Dilation, 196, 207 Dilution, 48, 207 Diphenylamine, 139, 207 Diploid, 208, 239, 240 Direct, iii, 14, 22, 55, 131, 161, 208, 245, 246, 254 Disease Progression, 25, 208, 260 Disease-specific survival, 88, 208 Disorientation, 202, 208 Dissociation, 188, 208 Distal, 26, 55, 204, 208, 244 Diuresis, 196, 208 DNA Topoisomerase, 208, 216 Docetaxel, 68, 115, 116, 120, 124, 125, 129, 131, 208 Domestic Violence, 16, 208 Dopamine, 201, 208 Dosage Forms, 136, 139, 140, 208 Dose-dependent, 9, 209 Double-blinded, 29, 209 Drive, ii, vi, 4, 61, 103, 209, 226 Drug Delivery Systems, 136, 209 Drug Design, 54, 209 Drug Interactions, 162, 209 Drug Tolerance, 209, 256 Duct, 198, 209, 213, 249 Duodenum, 194, 209, 236, 253 Dwarfism, 34, 209 Dyslipidemia, 14, 47, 209 Dyspareunia, 209, 212 Dysplasia, 72, 209 Dystrophic, 71, 209 E Eating Disorders, 159, 209 Eccentricity, 25, 209 Echocardiography, 18, 25, 209 Edema, 4, 209, 231, 235 Effector, 28, 187, 201, 209 Efficacy, 6, 8, 17, 24, 25, 32, 38, 47, 50, 51, 57, 58, 61, 72, 136, 209, 210 Elastin, 201, 210 Electrocardiogram, 32, 210 Electrocoagulation, 201, 210 Electrolyte, 204, 210, 225, 251 Electrons, 192, 193, 210, 224, 235, 245 Electrophysiological, 210, 259

Electroplating, 197, 210 Embryo, 44, 189, 195, 198, 210, 214, 216, 222, 231, 235, 242, 252, 254 Embryo Transfer, 210, 242 Embryology, 210, 233 Emulsion, 210, 214 Enanthate, 8, 144, 210 Endarterectomy, 190, 210 Endemic, 210, 252 Endocrine Glands, 210, 236, 237 Endocrine System, 25, 210, 211, 233 Endocrinology, 12, 40, 65, 72, 73, 74, 75, 76, 78, 79, 82, 85, 89, 94, 98, 100, 104, 211 Endometrial, 16, 23, 45, 58, 63, 118, 124, 211 Endometriosis, 17, 109, 130, 142, 211, 232, 258 Endometrium, 11, 23, 211, 229, 258 Endothelial cell, 132, 211 Endothelium, 9, 33, 132, 211, 233, 240 Endothelium, Lymphatic, 211 Endothelium, Vascular, 211 Endothelium-derived, 211, 233 Endotoxic, 211, 226 Endotoxins, 202, 211 End-stage renal, 139, 200, 211, 240 Energy balance, 30, 211, 226 Enhancer, 136, 211 Enteral Nutrition, 26, 211 Environmental Health, 168, 170, 211 Enzymatic, 196, 197, 202, 205, 206, 211, 214 Enzyme, 132, 144, 208, 209, 211, 218, 231, 239, 240, 243, 244, 246, 247, 253, 255, 257, 260 Epidemic, 24, 211, 252 Epidemiological, 13, 28, 37, 46, 212 Epithelial, 8, 82, 84, 138, 187, 212 Epithelial Cells, 8, 212 Epithelial ovarian cancer, 82, 212 Epithelium, 8, 67, 139, 211, 212, 243 Equilenin, 8, 212 Equilin, 8, 212 Erythrocytes, 190, 195, 212 Esophagus, 207, 212, 253, 259 Estradiol, 9, 11, 21, 28, 41, 43, 44, 47, 55, 137, 140, 162, 212, 250 Estramustine, 115, 116, 120, 124, 125, 131, 212 Estrogen Antagonists, 52, 212 Estrogen receptor, 19, 21, 31, 45, 49, 52, 55, 79, 137, 200, 212 Estrogen receptor positive, 52, 212

268 Hormone Therapy

Estrogen Replacement Therapy, 8, 19, 20, 25, 28, 31, 48, 212 Estrone, 41, 59, 212 Eukaryotic Cells, 206, 212, 222 Evoke, 212, 253 Excipient, 140, 212, 257 Excitability, 52, 212 Excitatory, 213, 217, 233 Excitatory Amino Acids, 213, 233 Excrete, 192, 213, 225 Exercise Test, 26, 213 Exhaustion, 191, 213 Exisulind, 115, 116, 213 Exocrine, 213, 236 Exogenous, 11, 17, 42, 48, 58, 89, 194, 213, 216 Exon, 10, 213 Expiration, 213, 248 External radiation, 213 External-beam radiation, 118, 213, 224, 245, 261 Extracellular, 203, 213, 214, 251, 255 Extreme obesity, 23, 213 Exudate, 213, 257 F Family Planning, 144, 169, 213 Fat, 14, 26, 29, 30, 47, 53, 63, 85, 141, 187, 188, 195, 204, 213, 226, 248, 251, 253, 257 Fatigue, 34, 73, 213, 218 Femoral, 35, 213 Femur, 35, 51, 213 Fertilization in Vitro, 213, 242 Fetal Development, 50, 214 Fetus, 22, 195, 214, 239, 242, 252, 253, 259 Fibrin, 195, 214, 240, 255, 256 Fibrinogen, 48, 58, 214, 240, 255 Fibrinolysis, 30, 214 Fibrinolytic, 30, 48, 214 Fibroblasts, 214, 223 Fibroid, 214, 226 Finasteride, 126, 214 Fixation, 148, 214 Fluorine, 52, 214 Flutamide, 21, 88, 115, 116, 118, 119, 120, 122, 125, 126, 127, 214 Folate, 14, 214 Fold, 39, 214 Folic Acid, 214 Follicles, 12, 43, 215 Forearm, 195, 215, 245, 246 Fovea, 214, 215

G Gallbladder, 187, 194, 207, 215 Gamma Rays, 215, 245 Ganglia, 187, 215, 232, 238 Gap Junctions, 215, 254 Gas, 189, 197, 207, 214, 215, 220, 228, 233, 259 Gas exchange, 215, 259 Gastric, 193, 208, 215 Gastrin, 215, 219 Gastroenteritis, 196, 215 Gastrointestinal, 26, 196, 211, 214, 215, 226, 250, 253, 258 Gastrointestinal tract, 26, 214, 215, 226, 250, 258 Gastrostomy, 211, 215 Gene, 6, 10, 19, 31, 34, 41, 43, 45, 47, 54, 55, 56, 90, 150, 189, 194, 215, 216, 219, 250 Gene Amplification, 45, 215 Gene Expression, 34, 44, 47, 56, 215 Gene Targeting, 43, 216 General practitioner, 150, 216 Genetics, 73, 84, 139, 148, 203, 216 Genistein, 46, 216 Genital, 200, 216, 259 Genotype, 6, 19, 20, 37, 216, 238 Geriatric, 43, 99, 216 Germ Cells, 216, 229, 234, 235, 252, 255 Germ Layers, 195, 216 Gestation, 22, 49, 216, 237, 239, 252 Gestational, 50, 95, 101, 216 Gestational Age, 50, 95, 101, 216 Gland, 8, 13, 33, 45, 144, 188, 199, 204, 216, 220, 227, 232, 236, 239, 243, 246, 249, 253, 256 Glomerular, 138, 216, 225, 247 Glomerulus, 216 Glucocorticoid, 24, 36, 50, 64, 207, 216, 219, 242 Gluconeogenesis, 12, 216 Glucose, 21, 26, 28, 34, 47, 59, 75, 99, 136, 140, 198, 207, 216, 217, 218, 223, 246, 249 Glucose Intolerance, 75, 207, 216 Glucose tolerance, 47, 216 Glucose Tolerance Test, 48, 216, 217 Glutamic Acid, 214, 217, 243 Glutamine, 26, 217 Glycoprotein, 214, 217, 250, 258 Gonad, 217 Gonadal, 8, 10, 13, 16, 24, 54, 217, 253 Gonadorelin, 217, 226, 232, 258

Index 269

Gonadotropin, 11, 12, 17, 44, 74, 98, 196, 217, 226 Goserelin, 115, 118, 119, 122, 217 Governing Board, 217, 241 Government Agencies, 27, 217, 241 Gp120, 217, 237 Grade, 39, 68, 217, 243 Graft, 48, 217, 222, 231 Grafting, 204, 217 Granulocytes, 217, 260 Growth Disorders, 70, 217 Growth factors, 70, 218 Growth Plate, 4, 218 Guanylate Cyclase, 218, 233 H Half-Life, 11, 218 Haploid, 218, 239, 240 Haptens, 188, 218 Headache, 4, 196, 218 Headache Disorders, 218 Health Education, 53, 147, 218 Health Policy, 27, 218 Health Status, 24, 218 Heart attack, 93, 197, 218 Heart failure, 19, 77, 218 Heart Valves, 193, 218 Heme, 205, 218 Hemodialysis, 36, 62, 67, 85, 90, 207, 218, 225 Hemoglobin, 190, 194, 212, 218, 255 Hemorrhage, 203, 204, 210, 218, 219, 231, 253 Hemostasis, 219, 250, 255 Hepatic, 12, 26, 34, 79, 216, 219 Heredity, 215, 216, 219 Heterogeneity, 139, 188, 219 Heterogenic, 219 Heterogenous, 138, 219 Hirsutism, 205, 219, 220 Histology, 219, 236 Homeostasis, 36, 219 Homogeneous, 203, 219, 238 Homologous, 10, 189, 205, 216, 219, 249, 254 Hormonal therapy, 42, 52, 56, 131, 137, 219, 228, 256 Human growth hormone, 4, 66, 72, 73, 79, 83, 95, 96, 98, 104, 140, 141, 158, 219 Hybridomas, 219, 223 Hydrocortisone, 33, 219 Hydrogel, 136, 220

Hydrogen, 187, 193, 196, 197, 207, 220, 226, 230, 233, 235, 238, 244 Hydrolysis, 8, 194, 198, 200, 220, 226, 241, 244 Hydrophilic, 220 Hydrophobic, 220, 226 Hydroxylation, 196, 220 Hydroxylysine, 201, 220 Hydroxyproline, 201, 220 Hyperandrogenism, 44, 220 Hypercalcemia, 24, 57, 220 Hypercalciuria, 57, 220 Hypercholesterolemia, 131, 209, 220, 237 Hyperglycemia, 9, 151, 220 Hyperlipidemia, 209, 220 Hyperplasia, 74, 139, 220 Hyperreactive, 49, 220 Hypersecretion, 11, 44, 220 Hypersensitivity, 55, 220, 248 Hypertelorism, 220, 233 Hypertension, 6, 14, 18, 50, 70, 143, 197, 218, 220 Hyperthermia, 148, 220 Hypertriglyceridemia, 209, 221 Hypertrophy, 138, 194, 220, 221 Hypnotic, 5, 51, 193, 221, 255 Hypoglycemia, 22, 75, 221 Hypogonadism, 24, 221 Hypophysis, 221, 250 Hypothalamic, 12, 33, 221 Hypothalamus, 67, 207, 217, 221, 239, 253, 255 Hysterectomy, 17, 221 I Id, 105, 108, 175, 176, 182, 184, 221 Idiopathic, 25, 70, 74, 77, 79, 86, 94, 221 Ifosfamide, 36, 221 Ileal, 26, 221 Ileum, 221, 260 Imaging procedures, 221, 257 Immaturity, 151, 221 Immune function, 13, 27, 34, 221 Immune response, 129, 188, 191, 193, 204, 218, 221, 253, 258, 260 Immune system, 15, 84, 114, 130, 141, 191, 193, 194, 221, 222, 227, 228, 232, 259, 260 Immunity, 188, 221, 223 Immunization, 221, 222, 242 Immunodeficiency, 27, 221 Immunogenic, 221, 226 Immunoglobulin, 191, 221, 231 Immunohistochemistry, 47, 221

270 Hormone Therapy

Immunologic, 199, 216, 221, 222, 245 Immunology, 188, 222 Immunosuppressive, 205, 216, 221, 222 Immunotherapy, 84, 194, 222 Impairment, 30, 34, 51, 194, 222, 229 Implant radiation, 222, 224, 245, 261 Impotence, 39, 222 In situ, 45, 222 In Situ Hybridization, 45, 222 In vitro, 19, 22, 23, 26, 44, 57, 58, 61, 74, 210, 222, 258 In vivo, 9, 10, 22, 23, 27, 53, 57, 61, 222 Incision, 222, 224, 243, 248 Incontinence, 39, 156, 222 Indicative, 148, 222, 237, 259 Indolent, 39, 222 Induction, 12, 55, 144, 190, 222, 235, 243, 253 Infarction, 82, 222, 247 Infection, 12, 24, 27, 37, 194, 199, 205, 215, 221, 222, 227, 237, 248, 253, 260 Infertility, 10, 11, 12, 17, 44, 53, 109, 126, 222, 235, 259 Infestation, 208, 222 Inflammation, 68, 130, 151, 187, 191, 192, 213, 215, 219, 223, 237, 243, 248, 253 Ingestion, 217, 223, 240, 255 Initiation, 8, 21, 25, 36, 56, 97, 223, 257 Initiator, 223 Inlay, 223, 248 Inorganic, 200, 223, 238 Insight, 22, 33, 45, 223 Insomnia, 38, 54, 223 Insulin-dependent diabetes mellitus, 223 Insulin-like, 70, 97, 100, 223 Interferon, 223, 227 Interleukin-1, 129, 223 Interleukin-12, 129, 223 Interleukin-2, 223 Interleukin-6, 61, 223 Intermittent, 84, 223, 238 Internal Medicine, 18, 62, 74, 75, 80, 81, 87, 91, 93, 97, 211, 223 Internal radiation, 118, 223, 224, 245, 261 Interstitial, 196, 224, 247, 261 Intestinal, 26, 54, 196, 216, 224, 228 Intestine, 26, 195, 201, 224, 225 Intoxication, 224, 260 Intracellular, 9, 144, 196, 222, 224, 233, 246 Intramuscular, 8, 224, 236 Intramuscular injection, 8, 224 Intraocular, 224, 256

Intraocular pressure, 224, 256 Intravascular, 48, 224, 235 Intravenous, 48, 62, 224, 236 Intrinsic, 188, 224, 246 Intubation, 198, 224 Invasive, 38, 41, 221, 224, 228, 243 Involuntary, 224, 231 Iodine, 53, 224 Ionizing, 189, 224, 228, 245 Ions, 193, 196, 208, 210, 220, 224, 244 Irradiation, 99, 104, 224, 261 Ischemia, 9, 48, 71, 193, 224, 231, 233, 247 Ischemic stroke, 30, 224 Islet, 75, 225 J Jejunostomy, 211, 225 Joint, 39, 57, 151, 192, 225, 254 K Kb, 168, 225 Ketoconazole, 117, 225 Kidney Disease, 95, 133, 138, 168, 225 Kidney Failure, 4, 211, 225 Kidney Failure, Acute, 225 Kidney Failure, Chronic, 225 Kinetic, 29, 224, 225 L Labile, 201, 225 Lactation, 225, 243 Laparoscopy, 17, 225 Large Intestine, 201, 207, 224, 225, 246, 251 Laser Surgery, 170, 225 Latent, 225, 242 Laxative, 225, 257 Leiomyoma, 42, 214, 226, 251 Leptin, 72, 85, 226 Lesion, 204, 226, 227 Lethal, 10, 43, 226 Leukemia, 115, 116, 117, 118, 120, 121, 125, 126, 127, 128, 200, 226 Leukocytes, 195, 199, 217, 226, 258 Leuprolide, 115, 118, 119, 122, 124, 125, 127, 226 Libido, 12, 190, 226 Library Services, 182, 226 Ligament, 226, 243 Ligands, 52, 226 Linkage, 6, 198, 226 Lipid, 4, 18, 32, 47, 53, 75, 81, 86, 192, 223, 226, 236, 257 Lipid A, 18, 47, 226 Lipid Peroxidation, 226, 236 Lipolysis, 26, 226

Index 271

Lipopolysaccharides, 226 Lipoprotein, 4, 48, 58, 131, 209, 226, 227 Lipoprotein(a), 58, 226 Liver, 26, 34, 85, 187, 194, 196, 205, 207, 210, 214, 215, 216, 219, 226, 227, 242, 246, 247, 249, 258 Liver scan, 227, 249 Lobe, 219, 227 Localization, 51, 52, 221, 227 Localized, 39, 63, 68, 69, 87, 88, 89, 206, 214, 219, 222, 227, 239 Longitudinal study, 29, 38, 90, 227 Loop, 56, 227 Low-density lipoprotein, 18, 48, 209, 226, 227 Lumbar, 51, 84, 227 Lupus, 57, 201, 227 Lutein Cells, 227, 243 Lymph, 45, 193, 199, 200, 211, 227, 232, 233 Lymph node, 193, 199, 227, 232, 233 Lymphatic, 211, 222, 227, 252, 256 Lymphatic system, 227, 252, 256 Lymphoblastic, 127, 227 Lymphoblasts, 187, 227 Lymphocyte, 191, 227, 228 Lymphocytic, 127, 227 Lymphoid, 191, 227, 228 Lymphoma, 227, 228 M Macrophage, 223, 228 Macula, 50, 215, 228 Magnetic Resonance Imaging, 228, 249 Malabsorption, 228, 250 Malabsorption syndrome, 228, 250 Malignant, 61, 85, 187, 192, 217, 228, 232, 245, 254 Malnutrition, 36, 193, 228 Mammary, 8, 137, 204, 228, 246, 254 Mandible, 189, 228, 248 Man-made, 198, 228 Mastectomy, 128, 228 Maternal Exposure, 22, 228 Maximum Tolerated Dose, 24, 209, 228 Medial, 15, 228, 234, 252 Mediate, 47, 52, 55, 60, 208, 228 Mediator, 144, 223, 228, 250 Medical oncologist, 36, 228 Medical Records, 228, 248 Medical Staff, 209, 228 MEDLINE, 169, 228 Medroxyprogesterone, 29, 48, 84, 162, 229

Medroxyprogesterone Acetate, 29, 84, 229 Megestrol, 124, 229 Meiosis, 229, 254 Memory, 5, 9, 20, 28, 34, 51, 58, 65, 206, 229 Menarche, 90, 229 Meninges, 198, 199, 204, 229 Menorrhagia, 42, 229 Menstrual Cycle, 21, 42, 229, 242 Menstruation, 189, 229, 234, 242 Mental Disorders, 133, 229, 242, 244 Mental Health, iv, 5, 16, 133, 168, 171, 229, 242, 244 Mental Retardation, 229, 234 Mentors, 32, 229 Meta-Analysis, 70, 229 Metabolite, 51, 194, 196, 212, 229 Metastasis, 229, 232 Metastatic, 41, 46, 56, 57, 69, 72, 88, 114, 115, 116, 121, 122, 125, 129, 217, 229 MI, 49, 74, 85, 185, 229 Microbe, 230, 256 Microbiology, 187, 230 Microorganism, 201, 230, 260 Microscopy, 9, 230 Microtubules, 230, 236 Midaxillary line, 230, 260 Milliliter, 195, 230 Millimeter, 230, 260 Mineralization, 26, 230 Minority Groups, 35, 230 Mitochondrial Swelling, 230, 232 Mitosis, 192, 230 Mitotic, 208, 230, 231 Mitotic inhibitors, 208, 230 Mitoxantrone, 120, 121, 125, 230 Modeling, 48, 209, 230 Modification, 20, 53, 230, 245 Modulator, 230 Monitor, 41, 42, 50, 205, 230, 234 Monoclonal, 121, 129, 219, 224, 231, 245, 257, 261 Monoclonal antibodies, 121, 129, 231, 257 Monocyte, 24, 231 Monotherapy, 83, 231 Morphological, 210, 231 Morphology, 10, 15, 68, 231 Morula, 195, 231 Motility, 10, 231, 250 Mucosa, 26, 227, 231, 232, 243 Myocardial infarction, 37, 49, 80, 82, 204, 229, 231

272 Hormone Therapy

Myocardial Ischemia, 204, 231 Myocardial Reperfusion, 231, 247 Myocardial Reperfusion Injury, 231, 247 Myocardium, 19, 229, 231 N Nadir, 94, 231 Nafarelin, 17, 231 Naive, 28, 69, 232 Nasal Cavity, 232 Nasal Mucosa, 74, 232 Nasogastric, 211, 232 Natural killer cells, 223, 232 Nausea, 208, 215, 232, 258 Necrosis, 33, 192, 222, 229, 231, 232, 247 Need, 3, 4, 26, 55, 76, 92, 138, 144, 147, 150, 159, 170, 177, 188, 200, 212, 232, 256 Neonatal, 22, 72, 232 Neoplasia, 84, 232, 243 Neoplasms, 192, 217, 232, 245 Neoplastic, 190, 219, 220, 228, 232 Nephrectomy, 50, 232 Nephron, 50, 90, 138, 216, 232 Nephropathy, 225, 232 Nerve, 206, 228, 232, 241, 244, 248, 249, 253, 257 Nervous System, 15, 28, 54, 187, 188, 189, 193, 196, 198, 199, 201, 215, 217, 228, 232, 233, 238, 250 Neural, 21, 188, 232 Neuroendocrine, 6, 18, 21, 34, 233 Neurologic, 30, 233 Neuronal, 15, 52, 233 Neurons, 15, 201, 206, 213, 215, 233, 254 Neurophysiology, 16, 233 Neuroprotective Agents, 20, 233 Neuropsychological Tests, 20, 233 Neurosciences, 40, 233 Neurosecretory Systems, 211, 233 Neutrons, 189, 224, 233, 245 Nilutamide, 89, 120, 233 Nitric Oxide, 9, 131, 233 Nitrogen, 189, 190, 205, 212, 214, 217, 225, 233, 236, 258 Node-negative, 45, 233 Node-positive, 45, 233 Noonan Syndrome, 77, 233 Nuclear, 203, 210, 212, 215, 228, 232, 234, 243, 258 Nucleic acid, 222, 233, 234, 248 Nucleus, 192, 199, 205, 206, 207, 212, 215, 229, 233, 234, 243, 244 Nurse Practitioners, 36, 234

Nutritional Status, 36, 234 O Observational study, 30, 35, 42, 62, 96, 234 Oestradiol, 86, 104, 234 Ointments, 209, 234, 236 Oligomenorrhea, 234, 240 Oliguria, 225, 234 Oncologist, 57, 228, 234 Oocytes, 45, 234 Opacity, 206, 234 Ophthalmology, 214, 234 Optic Chiasm, 221, 234, 253 Orchiectomy, 121, 234 Osseointegration, 195, 235 Ossification, 235 Osteoarthritis, 54, 148, 235 Osteogenesis, 65, 78, 148, 195, 235 Osteogenesis Imperfecta, 65, 78, 148, 235 Osteoporosis, 22, 36, 37, 42, 58, 85, 143, 148, 188, 212, 235, 246 Outpatient, 28, 235 Ovarian Hyperstimulation Syndrome, 11, 12, 235 Ovaries, 21, 43, 212, 220, 235, 241, 247, 250 Ovary, 44, 67, 190, 204, 212, 217, 235 Overall survival, 45, 235 Overexpress, 46, 235 Ovulation, 11, 12, 43, 191, 200, 229, 235, 258 Ovulation Induction, 12, 235 Ovum, 204, 216, 231, 235, 242, 243, 258, 260 Oxidation, 14, 187, 192, 194, 205, 226, 235, 236 Oxidation-Reduction, 194, 235 Oxidative Stress, 33, 71, 236 Oxygen Consumption, 213, 236, 248 P Pacemaker, 54, 236 Paclitaxel, 23, 45, 122, 236 Palliative, 205, 229, 236, 255 Pamidronate, 50, 236 Pancreas, 187, 194, 207, 223, 225, 236, 258 Pancreatic, 21, 141, 236 Pancreatic Insufficiency, 22, 236 Paraffin, 45, 47, 236 Parathyroid, 37, 90, 96, 99, 196, 236, 255 Parathyroid Glands, 236 Parathyroid hormone, 37, 90, 96, 99, 196, 236 Parenteral, 26, 136, 236 Parenteral Nutrition, 26, 236

Index 273

Partial remission, 236, 247 Parturition, 236, 243 Patch, 237, 257 Pathogenesis, 7, 19, 237 Pathologic, 19, 187, 192, 194, 204, 220, 237, 247 Pathologic Processes, 192, 237 Pathophysiology, 12, 43, 49, 139, 237 Patient Compliance, 143, 237 Patient Education, 101, 174, 180, 182, 185, 237 Pectins, 140, 237 Pediatric Endocrinologist, 66, 104, 237 Pelvic, 17, 130, 156, 211, 237, 243 Penicillin, 191, 237 Penis, 202, 237, 238, 247 Peptide, 61, 226, 237, 241, 243, 244, 256 Peptide T, 61, 237 Perception, 26, 237, 249 Percutaneous, 32, 71, 237 Perinatal, 50, 237 Perineal, 237, 245 Periodontal disease, 189, 237 Periodontitis, 37, 237 Peripheral blood, 24, 58, 238 Peripheral Nervous System, 238, 253 Peripheral stem cell transplantation, 121, 238 Peritoneal, 4, 75, 192, 238 Peritoneal Cavity, 192, 238 Peritoneal Dialysis, 4, 75, 238 Peritoneum, 238, 248 Petroleum, 236, 238 PH, 29, 41, 66, 170, 195, 238 Phallic, 214, 238 Pharmaceutical Preparations, 198, 238 Pharmaceutical Solutions, 209, 238 Pharmacokinetic, 238 Pharmacologic, 9, 35, 218, 238, 256 Phenotype, 6, 10, 28, 47, 58, 139, 234, 238 Phosphates, 9, 238 Phospholipids, 213, 226, 239 Phosphoprotein Phosphatase, 198, 239 Phosphorus, 196, 236, 239 Phosphorylation, 29, 55, 205, 239, 244 Photocoagulation, 201, 239 Physical Examination, 151, 216, 239 Physiologic, 6, 14, 74, 144, 188, 194, 200, 207, 214, 218, 229, 239, 246, 247 Physiology, 6, 11, 32, 34, 36, 54, 147, 151, 170, 197, 210, 211, 233, 239 Pilot study, 41, 57, 239

Pineal Body, 239 Pineal gland, 54, 239 Pituitary Gland, 4, 33, 61, 204, 217, 239 Placenta, 212, 239, 242 Placental Insufficiency, 21, 239 Plague, 33, 239 Plants, 189, 197, 201, 216, 231, 237, 239, 249, 257 Plaque, 190, 193, 239 Plasma cells, 191, 240 Plasma protein, 211, 240, 244 Plasmid, 215, 240 Plasmin, 240 Plasminogen, 30, 58, 240 Plasminogen Activators, 240 Platelet Activation, 48, 240 Platelet Aggregation, 190, 233, 240 Platelets, 48, 49, 233, 240, 255, 256 Platinum, 36, 200, 227, 240 Ploidy, 94, 240 Poisoning, 208, 215, 224, 232, 240 Policy Making, 27, 217, 240 Polycystic, 12, 44, 95, 98, 138, 220, 240 Polycystic Ovary Syndrome, 12, 220, 240 Polyethylene, 140, 241 Polyethylene Glycols, 140, 241 Polymers, 140, 241, 244 Polymorphism, 90, 241 Polypeptide, 111, 189, 201, 214, 240, 241, 243, 255 Polyposis, 201, 241 Polysaccharide, 191, 198, 241 Population Growth, 144, 241 Posterior, 190, 230, 236, 239, 241, 252 Postnatal, 241, 252 Postsynaptic, 241, 254 Post-translational, 190, 241, 250 Post-traumatic, 33, 218, 241 Potentiates, 23, 26, 223, 241 Practice Guidelines, 171, 174, 241 Precancerous, 58, 213, 241, 242 Preclinical, 7, 241 Precursor, 190, 205, 208, 209, 211, 240, 242, 243, 244, 258 Predisposition, 139, 242 Prednisolone, 242 Prednisone, 120, 121, 125, 242 Pregnancy Outcome, 45, 242 Pregnancy Tests, 216, 242 Pregnenolone, 142, 242 Premalignant, 241, 242, 243 Premenopausal, 42, 46, 60, 242

274 Hormone Therapy

Premenstrual, 142, 242 Prenatal, 50, 148, 210, 242 Pressoreceptors, 193, 242 Presynaptic, 10, 242, 254 Prevalence, 24, 35, 242 Primary endpoint, 51, 53, 242 Primary Prevention, 14, 33, 62, 91, 96, 242 Primary tumor, 47, 242 Probe, 39, 242 Progestogen, 16, 97, 175, 242 Progression, 7, 20, 24, 27, 38, 41, 46, 48, 53, 60, 81, 139, 190, 205, 243, 258 Progressive, 4, 25, 114, 123, 127, 128, 198, 200, 206, 209, 212, 217, 225, 232, 240, 243, 247 Prolactin, 56, 98, 243 Proline, 201, 220, 243 Promoter, 10, 243 Prophase, 234, 243, 254 Prophylaxis, 143, 243 Proportional, 215, 243 Prospective study, 26, 45, 86, 104, 227, 243 Prostate gland, 39, 243 Prostatectomy, 57, 116, 120, 157, 243, 245 Prostatic Hyperplasia, 243 Prostatic Intraepithelial Neoplasia, 68, 243 Prostatic Neoplasms, 212, 243 Prostatitis, 147, 243 Protease, 201, 243 Protein C, 189, 192, 226, 243, 258 Protein S, 26, 61, 150, 194, 219, 244, 249, 255 Protein-Tyrosine Kinase, 216, 244 Proteolytic, 201, 214, 240, 244 Prothrombin, 30, 40, 244, 255 Protocol, 8, 9, 11, 17, 41, 55, 244 Protons, 189, 220, 224, 244, 245 Proto-Oncogene Proteins, 236, 244 Proto-Oncogene Proteins c-mos, 236, 244 Proximal, 35, 51, 208, 232, 242, 244 Psychiatry, 5, 17, 51, 60, 214, 244 Psychic, 200, 226, 244, 250 Ptosis, 233, 244 Puberty, 28, 54, 73, 156, 232, 244, 258 Public Health, 14, 17, 23, 37, 38, 171, 244 Public Policy, 169, 244 Pulmonary, 85, 195, 203, 213, 218, 225, 234, 244, 253, 259 Pulmonary Artery, 195, 244, 259 Pulmonary Edema, 225, 244 Pulmonary Valve, 234, 244 Pulse, 53, 231, 245

Q Quality of Life, 6, 20, 24, 30, 32, 33, 41, 51, 54, 92, 126, 245 Quinones, 8, 245 R Race, 6, 245 Radial Artery, 53, 245 Radiation oncologist, 234, 245 Radical prostatectomy, 57, 86, 88, 116, 121, 126, 157, 245 Radioactive, 118, 195, 218, 220, 222, 223, 224, 227, 228, 231, 234, 245, 249, 254, 258, 261 Radiography, 216, 245 Radioimmunotherapy, 245 Radioisotope, 245, 257 Radiolabeled, 121, 224, 245, 261 Radiological, 237, 245 Radiotherapy, 39, 52, 88, 94, 95, 126, 148, 196, 224, 245, 261 Radius, 245, 246 Raloxifene, 18, 23, 59, 66, 68, 246, 250 Random Allocation, 246 Randomization, 12, 48, 246 Randomized clinical trial, 35, 39, 246 Receptor, 7, 8, 10, 21, 23, 26, 31, 34, 43, 44, 45, 52, 54, 56, 58, 60, 64, 80, 101, 108, 137, 142, 144, 187, 191, 208, 212, 217, 237, 246, 250 Receptor, Insulin, 44, 246 Receptors, Serotonin, 246, 250 Recombinant, 4, 11, 26, 36, 66, 70, 72, 73, 79, 84, 95, 98, 99, 104, 141, 246 Recombination, 10, 203, 216, 246 Recovery of Function, 15, 246 Rectal, 193, 246 Rectum, 31, 192, 195, 201, 207, 215, 222, 225, 243, 246 Recurrence, 17, 39, 86, 126, 157, 246 Reductase, 144, 214, 246 Refer, 1, 196, 201, 214, 227, 228, 232, 233, 245, 246 Refraction, 247, 252 Refractory, 24, 52, 129, 210, 247 Regeneration, 140, 247 Regimen, 17, 24, 25, 57, 114, 117, 118, 119, 127, 136, 210, 237, 247 Relapse, 55, 60, 120, 247 Relaxin, 11, 54, 247 Remission, 137, 246, 247 Renal failure, 36, 139, 140, 247 Renal Replacement Therapy, 36, 247

Index 275

Renin, 6, 11, 190, 247 Renin-Angiotensin System, 6, 247 Reperfusion, 9, 231, 247 Reperfusion Injury, 9, 247 Reproduction Techniques, 242, 247 Reproductive system, 243, 247 Research Design, 17, 40, 247 Resected, 39, 247 Resection, 26, 148, 170, 247, 250, 257 Residual disease, 39, 247 Resorption, 189, 247 Respiration, 6, 192, 197, 230, 248 Respiratory distress syndrome, 151, 248 Response rate, 137, 248 Restoration, 13, 73, 231, 247, 248 Retina, 234, 248, 249 Retinae, 228, 248 Retinoid, 24, 248 Retroperitoneal, 188, 248, 260 Retropubic, 243, 245, 248 Retropubic prostatectomy, 245, 248 Retrospective, 45, 248 Retrospective Studies, 45, 248 Retrospective study, 46, 248 Reversion, 55, 248 Rheumatic Diseases, 151, 248 Rheumatism, 248 Rheumatoid, 151, 201, 248 Rheumatoid arthritis, 151, 201, 248 Ribonucleic acid, 45, 248 Ribosome, 249, 257 Risk factor, 13, 23, 29, 36, 47, 49, 55, 59, 66, 101, 140, 151, 159, 243, 249 Rod, 148, 200, 249 S Saliva, 249 Salivary, 45, 205, 207, 249 Salivary glands, 205, 207, 249 Saphenous, 48, 204, 249 Saphenous Vein, 48, 204, 249 Saponins, 249, 253 Scans, 35, 58, 249 Schizoid, 249, 260 Schizophrenia, 249, 260 Schizotypal Personality Disorder, 249, 260 Sclerae, 235, 249 Screening, 13, 40, 200, 249 Scrotum, 205, 249, 254 Secretion, 11, 22, 55, 61, 188, 204, 209, 217, 220, 223, 225, 236, 249, 250 Secretory, 13, 243, 249, 254 Sedative, 5, 51, 193, 249

Sedentary, 7, 33, 249 Segregation, 246, 249 Seizures, 51, 250 Selective estrogen receptor modulator, 23, 246, 250, 254 Sella, 33, 239, 250 Semen, 243, 250 Senile, 235, 250 Sepsis, 26, 250 Sequence Homology, 237, 250 Serine, 217, 239, 244, 250 Serotonin, 101, 108, 246, 250, 258 Serous, 211, 250 Serum, 4, 7, 24, 28, 42, 59, 68, 72, 86, 88, 141, 190, 201, 217, 225, 227, 250, 258 Sex Characteristics, 190, 244, 250, 255 Sex Hormone-Binding Globulin, 71, 250 Sexually Transmitted Diseases, 138, 144, 250 Shock, 220, 250, 257 Short Bowel Syndrome, 26, 250 Side effect, 4, 17, 26, 98, 100, 136, 140, 143, 161, 188, 194, 205, 251, 256 Signs and Symptoms, 148, 247, 251 Skeletal, 7, 17, 35, 36, 51, 58, 72, 73, 190, 200, 209, 217, 233, 251 Skeleton, 213, 225, 251 Skin graft, 251, 252 Skull, 204, 251, 254 Sleep apnea, 38, 51, 251 Small intestine, 26, 200, 209, 219, 221, 224, 232, 251 Smooth muscle, 42, 189, 190, 196, 214, 226, 247, 251, 253 Smooth Muscle Tumor, 42, 214, 251 Social Environment, 245, 251 Social Work, 36, 251 Sodium, 136, 140, 251 Soft tissue, 195, 251 Somatic, 7, 200, 229, 230, 238, 251, 254 Specialist, 176, 207, 251 Species, 189, 198, 214, 215, 219, 229, 230, 231, 245, 250, 251, 253, 256, 257, 258, 260 Specificity, 45, 188, 251 Spectrum, 12, 73, 104, 225, 251 Sperm, 10, 144, 190, 199, 252, 254, 259 Sperm Maturation, 10, 252 Spermatids, 252 Spermatocytes, 10, 252 Spermatogenesis, 10, 144, 252 Spermatogonia, 252 Spermatozoa, 250, 252

276 Hormone Therapy

Sphenoid, 220, 250, 252 Spinal cord, 195, 198, 199, 229, 232, 233, 238, 252 Spleen, 205, 227, 252 Spontaneous Abortion, 242, 252 Sporadic, 143, 252 Staging, 39, 249, 252 Steel, 200, 252 Stem cell transplantation, 122, 252 Stem Cells, 43, 238, 252 Stents, 148, 170, 252 Sterile, 10, 236, 252 Sterility, 67, 68, 70, 71, 74, 83, 86, 87, 90, 100, 101, 108, 205, 222, 252 Steroid, 6, 9, 12, 13, 14, 15, 24, 44, 50, 137, 138, 142, 144, 190, 204, 212, 242, 249, 252, 253 Steroid therapy, 50, 253 Stillbirth, 242, 253 Stimulant, 196, 253 Stimulus, 11, 60, 209, 253, 255 Stomach, 187, 207, 212, 215, 217, 219, 232, 238, 251, 252, 253 Stool, 222, 225, 253 Stress, 18, 25, 32, 151, 204, 215, 232, 236, 242, 248, 253 Stricture, 147, 253 Stroke, 19, 30, 49, 82, 92, 133, 156, 157, 168, 197, 224, 233, 253 Stromal, 211, 253 Subacute, 222, 253 Subarachnoid, 218, 253 Subclinical, 46, 53, 222, 250, 253 Subcutaneous, 145, 187, 209, 226, 236, 253, 260 Sublingual, 136, 253 Substance P, 68, 229, 242, 249, 253 Substrate, 132, 253 Superovulation, 11, 253 Supplementation, 6, 22, 33, 35, 253 Support group, 170, 253 Suppression, 12, 20, 55, 114, 190, 204, 253 Suprachiasmatic Nucleus, 54, 253 Surfactant, 151, 253 Survival Rate, 235, 254 Symphysis, 243, 254 Symptomatic, 42, 48, 60, 99, 254 Synapses, 15, 28, 254 Synapsis, 254 Synaptic, 41, 72, 254 Synaptic Vesicles, 254 Synergistic, 243, 254

Systemic, 14, 37, 162, 192, 195, 201, 222, 224, 242, 245, 254, 259, 261 Systolic, 87, 220, 254 T Tamoxifen, 21, 46, 47, 52, 59, 124, 250, 254 Technetium, 52, 254 Telomerase, 43, 254 Temporal, 29, 218, 254 Teratogens, 139, 254 Testicles, 54, 190, 205, 234, 249, 254, 259 Testicular, 10, 53, 205, 255 Testis, 144, 190, 212, 255 Tetany, 236, 255 Tetracycline, 56, 255 Thalassemia, 194, 255 Thalidomide, 116, 255 Therapeutics, 163, 255 Thigh, 48, 213, 255 Third Ventricle, 221, 239, 255 Thorax, 187, 227, 255 Threonine, 237, 239, 244, 250, 255 Threshold, 26, 55, 59, 212, 220, 255 Thrombin, 214, 240, 243, 244, 255 Thrombocytes, 240, 255 Thromboembolism, 39, 80, 81, 82, 255 Thrombolytic, 240, 255 Thrombophilia, 39, 255 Thrombosis, 58, 84, 244, 253, 255 Thrombus, 49, 204, 222, 225, 231, 240, 255, 256 Thymus, 140, 142, 221, 227, 256 Thyroid, 34, 67, 98, 141, 224, 236, 256, 258 Thyroid Gland, 236, 256 Thyroid Hormones, 256, 258 Thyrotropin, 98, 256 Thyroxine, 256 Tin, 240, 256 Tissue Transplantation, 140, 256 Tolerance, 48, 216, 256 Tomography, 53, 59, 256 Tonometry, 53, 256 Tooth Preparation, 187, 256 Topical, 192, 208, 236, 256 Total androgen blockade, 94, 256 Toxic, iv, 203, 206, 209, 221, 228, 256 Toxicity, 60, 138, 209, 228, 256 Toxicokinetics, 256 Toxicology, 75, 170, 256 Toxins, 191, 211, 222, 231, 245, 256 Trace element, 214, 256, 257 Tracer, 59, 257 Trachea, 256, 257

Index 277

Traction, 200, 257 Tragacanth, 140, 257 Transcriptase, 254, 257 Transcription Factors, 55, 198, 257 Transdermal, 136, 257 Transfection, 47, 56, 194, 257 Translation, 27, 257 Translational, 58, 257 Transmitter, 187, 208, 213, 228, 254, 257 Transplantation, 4, 25, 26, 64, 66, 72, 82, 98, 140, 200, 210, 221, 225, 238, 257 Transurethral, 148, 170, 243, 257 Transurethral Resection of Prostate, 243, 257 Trastuzumab, 129, 257 Trauma, 232, 233, 246, 257 Treatment Failure, 47, 257 Triad, 159, 257 Triglyceride, 4, 53, 142, 221, 257 Triptorelin, 126, 258 Trophoblast, 195, 258 Tryptophan, 201, 250, 258 Tuberculosis, 203, 227, 258 Tumor marker, 194, 258 Tumor model, 7, 24, 47, 53, 258 Tumor Necrosis Factor, 255, 258 Tumor-derived, 8, 258 Tyrosine, 208, 244, 246, 258 U Ultrasonography, 33, 170, 216, 258 Unconscious, 221, 258 Uranium, 254, 258 Urea, 225, 258 Uremia, 4, 225, 247, 258 Urethra, 193, 194, 237, 243, 257, 258, 259 Urinary, 39, 101, 118, 126, 147, 156, 197, 222, 234, 243, 248, 258, 259 Urinary tract, 101, 258, 259 Urine, 11, 42, 56, 192, 193, 194, 195, 204, 205, 208, 212, 220, 222, 225, 234, 258, 259 Urologist, 57, 259 Urology, 39, 60, 63, 80, 82, 86, 87, 88, 89, 90, 94, 259 Uterus, 29, 42, 44, 58, 199, 204, 211, 214, 221, 226, 229, 235, 242, 247, 259

V Vaccine, 129, 188, 244, 258, 259 Vagina, 143, 199, 207, 229, 247, 259 Vaginal, 151, 259 Valves, 193, 259 Varices, 193, 259 Vascular, 5, 9, 33, 38, 48, 53, 131, 193, 211, 218, 222, 233, 239, 240, 242, 256, 259 Vascular Resistance, 193, 259 Vasectomy, 145, 259 Vasodilator, 132, 196, 208, 231, 259 Vasomotor, 131, 143, 212, 259 Vasopressor, 33, 259 Vein, 48, 224, 234, 249, 259 Venous, 19, 39, 80, 81, 82, 93, 244, 259 Venous blood, 40, 259 Ventricle, 244, 245, 254, 255, 259 Ventricular, 18, 20, 25, 33, 231, 259 Ventricular Function, 20, 25, 33, 259 Venules, 195, 211, 259 Vertebrae, 151, 252, 259 Vertebral, 90, 259 Veterinary Medicine, 169, 259 Viral, 12, 24, 27, 260 Viral Load, 24, 27, 260 Virilism, 220, 260 Virulence, 193, 256, 260 Virus, 27, 199, 211, 217, 240, 260 Visceral, 30, 53, 238, 260 Visceral fat, 30, 260 Vitro, 23, 260 Vivo, 22, 24, 28, 57, 260 W Waist circumference, 53, 260 Watchful waiting, 170, 260 Weight Gain, 53, 159, 260 Weight-Bearing, 235, 260 White blood cell, 129, 187, 191, 195, 199, 200, 226, 227, 228, 231, 232, 240, 260 Windpipe, 256, 260 Withdrawal, 90, 94, 98, 260 Womb, 247, 259, 260 X Xenograft, 191, 258, 260 X-ray therapy, 224, 261 Y Yeasts, 238, 261

278 Hormone Therapy

Index 279

280 Hormone Therapy