Benign Prostatic Hyperplasia - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

BENIGN PROSTATIC HYPERPLASIA A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E F...

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

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

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

Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Benign Prostatic Hyperplasia: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-497-00132-2 1. Benign Prostatic Hyperplasia-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 benign prostatic hyperplasia. 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 BENIGN PROSTATIC HYPERPLASIA .......................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Benign Prostatic Hyperplasia ..................................................... 27 E-Journals: PubMed Central ....................................................................................................... 78 The National Library of Medicine: PubMed ................................................................................ 78 CHAPTER 2. NUTRITION AND BENIGN PROSTATIC HYPERPLASIA ............................................... 123 Overview.................................................................................................................................... 123 Finding Nutrition Studies on Benign Prostatic Hyperplasia .................................................... 123 Federal Resources on Nutrition ................................................................................................. 125 Additional Web Resources ......................................................................................................... 126 CHAPTER 3. ALTERNATIVE MEDICINE AND BENIGN PROSTATIC HYPERPLASIA ........................ 129 Overview.................................................................................................................................... 129 National Center for Complementary and Alternative Medicine................................................ 129 Additional Web Resources ......................................................................................................... 145 General References ..................................................................................................................... 149 CHAPTER 4. PATENTS ON BENIGN PROSTATIC HYPERPLASIA ..................................................... 151 Overview.................................................................................................................................... 151 Patents on Benign Prostatic Hyperplasia .................................................................................. 151 Patent Applications on Benign Prostatic Hyperplasia .............................................................. 164 Keeping Current ........................................................................................................................ 184 CHAPTER 5. BOOKS ON BENIGN PROSTATIC HYPERPLASIA ......................................................... 185 Overview.................................................................................................................................... 185 Book Summaries: Federal Agencies............................................................................................ 185 Book Summaries: Online Booksellers......................................................................................... 191 Chapters on Benign Prostatic Hyperplasia ................................................................................ 192 CHAPTER 6. MULTIMEDIA ON BENIGN PROSTATIC HYPERPLASIA .............................................. 201 Overview.................................................................................................................................... 201 Video Recordings ....................................................................................................................... 201 CHAPTER 7. PERIODICALS AND NEWS ON BENIGN PROSTATIC HYPERPLASIA ........................... 203 Overview.................................................................................................................................... 203 News Services and Press Releases.............................................................................................. 203 Newsletters on Benign Prostatic Hyperplasia ........................................................................... 205 Newsletter Articles .................................................................................................................... 205 Academic Periodicals covering Benign Prostatic Hyperplasia .................................................. 206 CHAPTER 8. RESEARCHING MEDICATIONS .................................................................................. 207 Overview.................................................................................................................................... 207 U.S. Pharmacopeia..................................................................................................................... 207 Commercial Databases ............................................................................................................... 208 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 213 Overview.................................................................................................................................... 213 NIH Guidelines.......................................................................................................................... 213 NIH Databases........................................................................................................................... 215 Other Commercial Databases..................................................................................................... 217 APPENDIX B. PATIENT RESOURCES ............................................................................................... 219 Overview.................................................................................................................................... 219 Patient Guideline Sources.......................................................................................................... 219 Finding Associations.................................................................................................................. 231 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 233 Overview.................................................................................................................................... 233

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Preparation................................................................................................................................. 233 Finding a Local Medical Library................................................................................................ 233 Medical Libraries in the U.S. and Canada ................................................................................. 233 ONLINE GLOSSARIES................................................................................................................ 239 Online Dictionary Directories ................................................................................................... 242 BENIGN PROSTATIC HYPERPLASIA DICTIONARY ........................................................ 243 INDEX .............................................................................................................................................. 313

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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 benign prostatic hyperplasia 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 benign prostatic hyperplasia, 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 benign prostatic hyperplasia, 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 benign prostatic hyperplasia. Abundant guidance is given on how to obtain free-ofcharge 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 benign prostatic hyperplasia, 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 benign prostatic hyperplasia. 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. HYPERPLASIA

STUDIES

ON

BENIGN

PROSTATIC

Overview In this chapter, we will show you how to locate peer-reviewed references and studies on benign prostatic hyperplasia.

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

Non-medical Treatments for Benign Prostatic Hyperplasia: Balloons, Stents, Lasers and Cryosurgery Source: Current Opinion in Urology. 2(1): 8-11. February 1992. Summary: A majority of male patients with bladder outflow obstruction are treated satisfactorily by transurethral resection of the prostate (TURP). However, worries about mortality, morbidity and cost, combined with the progress of surgery towards minimally invasive therapies, have produced an array of potential alternatives. This article assesses those alternatives, including balloon dilatation, prostatic stenting, laser prostatotomy, and cryosurgical prostatectomy. The authors conclude that stents may

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prove to be a suitable alternative to TURP in patients who are not candidates for TURP. They note that long-term follow-up data is not presently available. 17 annotated references. (AA-M). •

Finasteride in the Treatment of Clinical Benign Prostatic Hyperplasia: A Systematic Review of Randomised Trials Source: BMC Nephrology. 2(14): [17 p.]. December 2002. Summary: Benign prostatic hyperplasia (BPH) affects older men. This systematic review study determined the effectiveness and adverse effects of finasteride, used to treat BPH. Of the studies found in the review, 3 trials had active controls and 19 had placebo. In placebo-controlled trials, 8,820 patients received finasteride 5 milligrams and 5,909 placebo over 3 to 48 months. Over 48 months, finasteride produced greater improvements in total symptom score, maximum urinary flow rate, and prostate volume. Significantly more sexual dysfunction, impotence, ejaculation disorder, and decreased libido occurred with finasteride at 12 months. Significantly fewer men treated with finasteride experienced acute retention or had surgery at 24 or 48 months than with placebo. The authors conclude that information from many patients in studies of high quality showed beneficial effects of finasteride in terms of symptoms, flow rate, and prostate volume. 6 figures. 4 tables. 57 references.

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Benign Prostatic Hypertrophy: 'Cost-Benefits' of Surgery Greater Than That of Drug Therapy Source: Drugs and Therapy Perspectives. 10(11): 13-15. November 24, 1997. Contact: Available from Adis International, Ltd. Suite F-10, 940 Town Center Drive, Langhorne, PA 19047. (800) 876-7082 or (215) 741-5200. Fax (215) 741-5251. Summary: Benign prostatic hypertrophy (BPH), defined as enlargement of the prostate with associated urinary symptoms, affects a large percentage of men over the age of 50 years. Treatment options include a wait and see approach with the introduction of surgery when symptoms become severe, or long term drug therapy, which is mainly indicated for men with moderate symptoms with the aim of circumventing the need for surgery. This article considers the cost benefits of surgery versus drug therapy for BPH. It is possible, and perhaps even likely, that efficient drug therapy itself will reduce the need for prostate surgery by lowering the general level of symptoms. Cost benefit considerations become unfavorable when they are applied to younger men with mild or no symptoms, and most men in this age group will probably object to taking drugs for years to prevent a benign condition such as BPH. Furthermore, cost benefit considerations are of questionable relevance in patients with severe symptoms, who are likely to require surgical management. Men with moderate symptoms of BPH are generally considered the best candidates for drug treatment. However, the distinction between mild and moderate symptoms is arbitrary, and there are wide differences in patient tolerance of symptoms. One possible benefit of closer long term followup of BPH as a result of drug treatment might be an increase in the early detection of prostate cancer. The author concludes that, until more potent drugs are introduced, transurethral resection and other alternative surgical treatments will continue to be the principal treatment modalities for symptomatic BPH. 9 references.

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Use of Hyperthermia for Benign Prostatic Hyperplasia Source: Current Opinion in Urology. 2(1): 12-17. February 1992.

Studies

5

Summary: Hyperthermia treatment of benign prostatic hyperplasia (BPH) is now being used after its earlier encouraging application in prostatic cancer. The author of this article reports on his experiences using a transrectal probe to deliver hyperthermia treatments. Objective and subjective improvement in obstructive and irritative symptoms has been reported in 40 to 60 percent of the cases. Other recently introduced machines use either the transrectal or the transurethral approach and induce higher temperatures than the original equipment. The author concludes that more time is needed to establish the optimum temperature in hyperthermia for BPH, the best and safest route to achieve this objective, how long each treatment should last, which patients should receive it, and how they should be selected and followed. 1 figure. 49 annotated references. (AA-M). •

Pathogenesis and Medical Management of Benign Prostatic Hyperplasia Source: Seminars in Nephrology. 14(6): 531-543. November 1994. Contact: Available from W.B. Saunders Company, Periodicals Department. 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-2452. Summary: In this article, the author considers the pathogenesis and medical management of benign prostatic hyperplasia (BPH). Topics covered include the natural history of BPH, including the role of normal aging; the etiology and pathogenesis of BPH; complications of BPH, including acute urinary retention, obstructive uropathy, chronic renal failure, urinary tract infection, bladder decompensation, and bladder calculi; patient evaluation, including patient history, the American Urological Association Symptom Index, physical examination, urinalysis, serum creatinine, and serum prostate-specific antigen (PSA); screening for prostate cancer; the role of urodynamics; cystourethroscopy; treatment options in BPH, including watchful waiting, transurethral resection of the prostate (TURP), and laser prostatectomy; and pharmacological therapy, with respect to reduction in prostatic size and reduction in prostatic smooth muscle tone. 9 tables. 76 references.

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Benign Prostatic Hyperplasia: Medical and Minimally Invasive Treatment Options Source: New England Journal of Medicine. 332 (2): 99-107. January 12, 1995. Summary: In this article, the author reviews the most important medical and minimally invasive treatments for men with symptomatic benign prostatic hyperplasia (BPH). Topics include evaluating treatment options; androgen-deprivation therapy; drugs that inhibit 5alpha-reductase activity; alpha-adrenergic-antagonist drugs; transurethral incision of the prostate; prostatic stents; microwave therapy; laser prostatectomy; and deciding on the right treatment for each patient. The author also considers at length the option of watchful waiting (no intervention beyond monitoring the patient at regular intervals). 3 figures. 5 tables. 36 references.

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Long-Term Effects of Finasteride on Invasive Urodynamics and Symptoms in the Treatment of Patients With Bladder Outflow Obstruction Due to Benign Prostatic Hyperplasia Source: Journal of Urology. 154(4): 1466-1469. October 1995. Contact: Available from Williams and Wilkins. 351 West Camden Street, Baltimore, MD 21201-2436. (800) 638-6423; in Maryland (800) 638-4007. Summary: In this article, the authors report on a study in which they assessed the long term effects of finasteride on bladder outlet obstruction and symptoms in the treatment

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Benign Prostatic Hyperplasia

of patients with benign prostatic hyperplasia. Of the original 36 patients assigned to treatment with 5 mg finasteride daily (group 1) or placebo (group 2) for 6 months, 27 completed an open extension study of 5 mg finasteride for 4 more years. The possible relief of bladder outlet obstruction was monitored with repeated pressure-flow studies at baseline, 6 months, and 4.5 years. Results showed that the treatment resulted in a further slight decrease in detrusor pressure at maximum flow rate in group 1 and a significant decrease in group 2 during the 4-year period, whereas improvement in maximum flow rate did not achieve statistical significance. Concomitantly, there was a significant improvement in obstructive and irritative symptoms. The authors conclude that finasteride decreases bladder outlet obstruction moderately and only occasionally relieves it completely. However, the decrease in obstruction achieved in many patients is sufficient to improve the symptoms significantly. The beneficial effect is long lasting. 2 figures. 2 tables. 24 references. (AA-M). •

Managing Patients With Benign Prostatic Hyperplasia Source: American Family Physician. 52(1): 135-142. July 1995. Summary: In this article, the authors review the management of patients with benign prostatic hyperplasia (BPH). With the use of a brief case example, the authors discuss diagnostic considerations, including the patient history; determining severity of symptoms; other conditions that can mimic BPH; complications that can arise from BPH; patient selection for prostate cancer screening; treatment options; the role of watchful waiting; medications used to treat BPH; the indications for transurethral resection (TURP); and new treatment modalities, including balloon dilation, microwave thermopathy, laser ablation, and urethral stents. One of the tables reprints the American Urological Association (AUA) Symptom Index in full. 2 figures. 6 tables. 29 references.

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Enlarged Prostate: What You Need to Know Source: Family Urology. 3(4): 9, 13, 16. 1998. Contact: Available from American Foundation for Urologic Disease. 1126 North Charles Street, Baltimore, MD 21201. (800) 242-2383 or (410) 468-1800. Fax (410) 468-1808. Website: www.afud.org. Summary: It is estimated that by the age of 60, half of all men will develop evidence of enlarged prostate (BPH, benign prostatic hyperplasia). Despite the large number of men affected by BPH, many men lack an awareness or knowledge about the condition and existing treatments. This article reviews BPH, how it happens, symptoms, and treatment options. BPH is a noncancerous enlargement of the prostate, a walnut-sized gland located just below the bladder (which stores urine); the prostate surrounds the urethra, the canal through which urine and semen pass out of the body. BPH symptoms occur when growth of muscular tissue and glands in the prostate combine and constrict the urethra. This can cause difficulty urinating, but generally does not interfere with sexual function. The author lists the typical symptoms of BPH. Diagnosis of BPH consists of a visit to a physician or urologist, a physical examination (including a digital rectal examination, or DRE), and patient history. If BPH is diagnosed, it only requires treatment if the symptoms are severe enough to be bothersome and if the function of the urinary tract is seriously affected. Treatment options include watchful waiting or a variety of surgical methods, including transurethral resection of the prostate (TURP), transurethral incision of the prostate (TUIP), laser surgery, open prostatectomy, transurethral microwave therapy (TUMT), and transurethral needle ablation (TUNA). Medications may also be used to treat BPH. The authors emphasize that effective

Studies

7

therapies exist to help treat the annoying symptoms associated with BPH. The article includes a sidebar describing information brochures that are available from the American Foundation for Urologic Disease. 1 figure. •

What We Do and Don't Know About Benign Prostatic Hyperplasia (editorial) Source: Current Opinion in Urology. 10(1): 1-2. January 2000. Contact: Available from Lippincott Williams and Wilkins. 241 Borough High Street, London, SE1 1GB, UK. +44 (0) 171940-7500. E-mail: [email protected]. Summary: Many urinary voiding complaints in elderly men are caused by benign prostatic hyperplasia (BPH); however, more recent research in this field indicates that some of these symptoms can be caused by bladder dysfunction. In an effort to clarify the differences, the author of this article reviews the current knowledge about BPH and its diagnosis and treatment. The author reminds readers to consider that age-related changes in bladder and central nervous system function, which may lead to lower urinary tract symptoms, may result in similar symptoms to those observed in patients with BPH. The lack of clear correlation between prostate size, urodynamic obstruction, and lower urinary tract symptoms has caused the questioning of the assumption that prostate growth is the key event. The author summarizes the current concepts regarding BPH treatment: watchful waiting is effective and appreciated by both patients and physicians; in case of a significant outlet obstruction, TURP is the most effective treatment, and risk has decreased considerably; and alternative minimally invasive therapies are especially attractive in high risk patients and those who prefer such a treatment over surgery. In addition, the author underscores the importance of adequate identification (diagnosis) before recommending the most appropriate therapy.

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Efficacy of Terazosin, Finasteride, or Both in Benign Prostatic Hyperplasia Source: New England Journal of Medicine. 335(8): 533-539. August 22, 1996. Summary: Men with benign prostatic hyperplasia (BPH) can be treated with alpha1adrenergic antagonist drugs that relax prostatic smooth muscle or with drugs that inhibit 5alpha-reductase and therefore reduce tissue androgen concentrations. This article reports on a study in which the authors compared the safety and efficacy of placebo, finasteride (5 mg daily), terazosin (10 mg daily), and the combination of both drugs in 1,229 men with BPH. American Urological Association symptom scores and peak urinary flow rates were determined at baseline and periodically for 1 year. The mean changes from baseline in the symptoms scores in the placebo, finasteride, terazosin, and combination-therapy groups were decreases of 2.6, 3.2, 6.1, and 6.2 points, respectively. The mean changes at 1 year in the peak urinary flow rates were increases of 1.4, 1.6, 2.7, and 3.2 ml per second, respectively. Finasteride had no more effect on either measure than placebo. In the placebo group, 1.6 percent of the men discontinued the study because of adverse effects, as did 4.8 to 7.8 percent of the men in the other three groups. The authors conclude that, in men with BPH, terazosin was effective therapy, whereas finasteride was not, and the combination of terazosin and finasteride was no more effective than terazosin alone. 2 figures. 3 table. 24 references. (AA-M).

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Treatment Choice for Benign Prostatic Hyperplasia: A Matter of Urologist Preference? Source: Journal of Urology. 161(1): 133-138. January 1999. Summary: New treatment modalities for benign prostatic hyperplasia (BPH) have considerably altered the decision making process in daily clinical practice. Guidelines

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Benign Prostatic Hyperplasia

provide a framework for treatment choice but leave much room for physician personal opinions. This article reports on a study that identified and quantified determinants of treatment choice for BPH among urologists focusing on urologist treatment preferences. The study population consisted of 670 consecutive patients with BPH, 50 years old or older, newly referred to 1 of 39 urologists in a stratified sample of 13 hospitals throughout The Netherlands. Data on patient characteristics were retrieved from patient questionnaires, medical records, and a urologist questionnaire. Urologist treatment preferences were inventoried using a mailed questionnaire. Among the patient characteristics, maximum flow rate, residual urine, and prostate volume were strongly associated with the probability of surgery and watchful waiting. However, the influence of urologist preferences on actual decisions was also significant. Adjusted for case mix, the differences in low and high preferences revealed a 2.2 times greater probability of surgery. For alpha blockers and finasteride these ratios were 1.8 and 9.4, respectively. An additional independent effect was seen for urologist extent of experience. The authors conclude that the influence of urologist personal preferences on treatment choice in BPH is considerable. Given the different efficacy and side effects of the various treatments, further consensus development is needed to enhance appropriate treatment decisions and eliminate undue costs. The article includes an appendix that reprints the urologist questionnaire. 2 figures. 3 tables. 13 references. (AA-M). •

Benign Prostatic Hyperplasia: Pathogenesis and Medical Therapy Source: Journal of the American Geriatric Society. 39: (12): 1208-1216. December 1991. Summary: Prostate disease is a frequent accompaniment of aging in men. This review article covers the pathogenesis and medical therapy for benign prostatic hyperplasia (BPH). The author focuses on the role of the testis, and particularly dihydrotestosterone (DHT), in the pathogenesis of BPH, since it provides a clear understanding of the rationale for many of the clinical trials to develop medical therapy for BPH. Topics include the relationship between the testis and the prostate, the DHT theory of the pathogenesis of BPH, the estrogen theory of the pathogenesis of BPH, a summary of the endocrine factors relating to this pathogenesis, the non-endocrine factors, treatment of BPH, androgen-withdrawal therapy and surgical castration, medical castration with progestational agents, androgen blockade, medical castration with gonadotropinreleasing hormone (GNRH), the clinical effects of estrogen withdrawal, and the current status of the non-surgical management of BPH. 3 figures. 1 table. 55 references.

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Is Transurethral Microwave Thermotherapy an Alternative to Medical Therapy for Patients with Benign Prostatic Hyperplasia? Source: Techniques in Urology. 6(4): 300-306. December 2000. Contact: Available from Raven Press, Ltd. 1185 Avenue of the Americas, New York, NY 10036. (800) 777-2836 or (212) 930-9500. Summary: Scientific evidence supports the safety and efficacy of transurethral microwave thermotherapy (TUMT) as well as medical therapy for the management of patients with benign prostatic hyperplasia (BPH). This article considers the fact that TUMT is increasingly considered as an alternative to medical management with alpha blockers or finasteride in patients with lower urinary tract symptoms of BPH. Enduring clinical benefits have been demonstrated after a single 1 hour microwave treatment session under topical anesthesia, and associated morbidity is low. Optimal results are obtained with the delivery of high thermal doses and accurate targeting of microwave energy. Extensive evidence from randomized clinical trials supports the safety and

Studies

9

efficacy of both microwave treatment and medical management. Randomized clinical trial data directly comparing these two approaches to BPH treatment have only recently become available. These data indicate that greater long term improvements in symptoms, peak urinary flow rates, and quality of life are attained with microwave treatment as compared with alpha blocker therapy. Furthermore, the rate of treatment failure is markedly lower in patients undergoing microwave versus alpha blocker treatment. However, the onset of action with alpha blockers is faster. Limitations of alpha blockers are side effects and lack of efficacy leading to treatment failure in some patients. Maximal effects of finasteride are modest and require months to be demonstrated, although the side effect profile and tolerability of this agent are favorable. Neoadjuvant and adjuvant alpha blocker therapy can accelerate symptom and flow rate improvement after microwave treatment. In contrast to medical management, microwave treatment is highly versatile, allowing patients over a broad range of baseline symptom severities and prostate sizes to be treated with a high probability of success. The author concludes that, compared with medical management, microwave treatment also appears to possess greater versatility, allowing patients who fall within a broad range of baseline symptom severities and prostate sizes to be treated with a high probability of success. 1 table. 40 references. •

Effect of Diabetes on Lower Urinary Tract Symptoms in Patients with Benign Prostatic Hyperplasia Source: Journal of Urology. 163(6): 1725-1729. June 2000. Contact: Available from Lippincott Williams and Wilkins. 12107 Insurance Way, Hagerstown, MD 21740. (800) 638-3030 or (301) 714-2334. Fax (301) 824-7290. Summary: Several studies have suggested a specific association between the presence or symptom intensity of benign prostatic hyperplasia (BPH) and diabetes, but no definitive conclusion has thus far been reached. This article reports on a study that examined the intensity of lower urinary tract symptoms in a large cohort of men with BPH, with and without diabetes. The authors then determined whether the alpha 1 adrenoceptor antagonist tamsulosin similarly improved those lower urinary tract symptoms in patients with BPH with or without diabetes. The International Prostate Symptom Score (IPSS), maximum flow rate, and postvoid residual (urine remaining in the bladder after urination) were determined in 9,856 men with clinically diagnosed BPH, of whom 1,290 also had diabetes, at baseline and after a 12 week, open label course of 0.4 mg of tamsulosin daily. Older age and IPSS were independently associated with a statistically significant increase in the odds ratio of having diabetes. Accordingly, men with diabetes had a significantly greater baseline IPSS and smaller maximum flow rate than nondiabetic patients on age adjusted analysis, while residual urine was not significantly altered. Tamsulosin markedly improved lower urinary tract symptoms. The extent of improvement was similar in men with and without diabetes. The authors conclude that the severity of lower urinary tract symptoms in patients with BPH and the likelihood of having diabetes are significantly associated. Within the limitations of an open label, observational study, tamsulosin appears to reduce lower urinary tract symptoms similarly in BPH patients with or without diabetes. 2 tables. 22 references.

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Use of Lasers as an Alternative Treatment for Patients With Benign Prostatic Hyperplasia Source: Journal of Urological Nursing. 13(1): 656-660. January-February-March 1994.

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Contact: Available from Journal of Urological Nursing, P.O. Box 408, Long Valley, NJ 07853-0408. (908) 852-8789. Summary: The authors of this article describe the use of lasers as an alterative treatment for patients with benign prostatic hyperplasia (BPH). They report on more than two years experience performing laser prostatectomy using the TULIP (transurethral laser prostatectomy) device, with careful follow-up on all of the patients. The authors note that the majority of the currently available lasers utilize the laser's ability to induce coagulative necrosis to achieve the desired clinical effect while minimizing morbidity to the patient. They report on a study that investigated the use of TULIP at 10 clinical sites across the U.S. The results show excellent clinical outcome with minimal morbidity following laser prostatectomy. The authors also stress the need for more extensive cancer screening in patients undergoing TULIP, as compared to those undergoing transurethral resection of the prostate (TURP), in whom a biopsy can be performed postoperatively. 1 table. 8 references. •

Minimally Invasive Treatment for Benign Prostatic Hyperplasia Source: Current Opinion in Urology. 8(1): 17-26. January 1998. Contact: Available from Lippincott Williams and Wilkins. 241 Borough High Street, London, SE1 1GB, UK. +44 (0) 171940-7500. E-mail: [email protected]. Summary: The choices for minimally invasive treatments for patients with benign prostatic hyperplasia (BPH) has increased during the past decade. This article reviews these treatment options. The energy sources used range from microwaves and radiofrequency waves to high intensity focused ultrasound, laser vaporization, laser coagulation, laser resection, and electrosurgical techniques. The authors review the particular advantages and disadvantages of each of these devices by summarizing the findings of recent, clinically significant studies. At present, the most intensively studied techniques are interstitial laser coagulation, holmium laser resection, and new approaches to transurethral electrosurgery. The authors conclude that there is now enough data available to allow comparisons between these minimally invasive techniques and the gold standard for treatment, transurethral resection of the prostate (TURP). Although the subjective response after TURP and minimally invasive procedures is comparable, improvements of flow and urodynamic (measurement of urinary flow and pressure during urination) parameters are nearly always better after TURP. Failure rates requiring reintervention are considerably higher than after TURP and many of these procedures have anatomical limitations. Minimally invasive procedures lead to a shift of the morbidity (complications) from the intraoperative time, which is reduced, to the postoperative phase. The postoperative phase can be characterized by a prolonged urinary retention, significant dysuria (pain on urination), and nocturia (urination at night). The authors note that improvements in TURP are resulting in a less invasive procedure for TURP itself, and improvements in perioperative care and anesthesia are reducing the risk of postoperative complications. 2 figures. 4 tables. 64 references (21 abstracts).

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Outcome Analysis of Minimally Invasive Treatments for Benign Prostatic Hyperplasia Source: Techniques in Urology. 5(1): 12-20. 1999. Contact: Available from Raven Press, Ltd. 1185 Avenue of the Americas, New York, NY 10036. (800) 777-2836 or (212) 930-9500.

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Summary: The choices of minimally invasive treatment modalities for patients with benign prostatic hyperplasia (BPH) has increased steadily during the past decade. The energy sources used range from microwaves and radiofrequency waves to high intensity focused ultrasound, with laser vaporization or coagulation or resection and electrosurgical techniques. This article reviews the large amount of data available and draws some conclusions concerning the present role of the 'gold standard' TURP (transurethral resection of the prostate) among the minimally invasive procedures. Although the subjective response after TURP and other minimally invasive procedures is comparable, improvements of flow and urodynamic parameters usually are more pronounced after TURP. Failure rates requiring reintervention (usually TURP) are considerable. Minimally invasive procedures lead to a shift of morbidity from the intraoperative phase, which is reduced (risk of bleeding, TUR syndrome, transfusion) to the postoperative phase. This postoperative period is characterized by prolonged urinary retention, significant dysuria (painful urination), and nocturia (urination at night). Recent advances in electrosurgical techniques, such as band TURP loops that facilitate coagulation due to the longer contact time between the electrode and the tissue, have the potential to convert TURP into a less invasive procedure. Finally, high energy TUMT (transurethral microwave thermotherapy) seems to offer a truly minimally invasive treatment combining efficacy and the need for topical anesthesia only. However, due to a lack of homogeneity of criteria for patient recruitment, parameters of evaluation, and adequate followup, accurate guidelines for appropriate patient management have not yet been established. 93 references. •

The Role of Dihydrotestosterone in Benign Prostatic Hyperplasia Source: Current Opinion in Urology. 2(1): 18-21. February 1992. Summary: The enzyme 5beta-reductase converts intraprostatic testosterone into the potent androgen dihydrotestosterone. This article discusses the role of dihydrotestosterone (DHT) in benign prostatic hyperplasia (BPH). Topics include androgen-dependent growth, the 5beta-reductase deficiency syndrome, development of a drug (finasteride) to inhibit 5beta-reductase production, and the biochemical and clinical efficacy of finasteride. The author focuses on the use of finasteride in early BPH to prevent further progression of the disease. 1 figure. 1 table. 17 references. (AA-M).

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Alpha1-Adrenergic Blockers in the Medical Management of Benign Prostatic Hyperplasia Source: Current Opinion in Urology. 2(1): 26-29. February 1992. Summary: The tension of human prostatic smooth muscle is mediated primarily by the alpha1-adrenoceptor. This article discusses randomized placebo-controlled double-blind research studies that have recently demonstrated the safety and efficacy of selective alpha1-adrenoceptor antagonists for the treatment of benign prostatic hyperplasia (BPH). The author reviews the clinical trials, evaluating selective alpha1-blockers in BPH reported between August 1, 1990 and July 31, 1991. Compounds included are terazosin (Hytrin), prazosin (Minipress), alfuzosin, and YM617. 14 annotated references. (AA-M).

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Understanding Microwave Therapy as a Treatment Option for Benign Prostatic Hyperplasia Source: Urologic Nursing. 17(2): 53-57. June 1997. Summary: The treatment of benign prostatic hyperplasia (BPH) is evolving from the traditional approach of watchful waiting followed by surgery when needed to a variety

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of less invasive alternatives. Microwave therapy is one of the most explored forms of heat-induced therapy of the prostate. This article provides an overview of microwave therapy and explains what the nurse and patient should be aware of as treatment decisions are made. The authors describe two different forms of microwave therapy: hyperthermia and transurethral thermotherapy. The authors focus on the recently approved transurethral thermotherapy and related patient implications. This procedure involves heating the prostate gland transurethrally to destroy prostatic tissue through tissue necrosis. A special microwave catheter placed in the patient's urethra carries the microwaves and a cooling system of sterile water, which keeps the urethral area cooler than 50 degrees Centigrade. This procedure is completed with a single, 1 hour treatment. Compared to transurethral prostatectomy, microwave therapy is significantly less costly to the hospital and patient because it is an outpatient procedure that does not require general anesthesia, it is a short procedure, and it requires minimal staffing. 3 figures. 12 references. (AA-M). •

New Drug Treatments For Benign Prostatic Hyperplasia Source: Medical Aspects of Human Sexuality. 26(1): 39-40, 42-44. January 1992. Summary: This article considers new drug treatments being used for benign prostatic hyperplasia (BPH). The author notes that the limitations of prostatectomy have sparked an aggressive search for nonsurgical alternatives that do not impair sexual functioning. Topics covered include the clinical symptoms of BPH; current treatment; the use of alpha-blockers, including phenoxybenzamine, prazosin, and terazosin; androgen suppression through surgical and medical castration, including the use of prostatic dihydrotestosterone (DHT); the role of hormonal therapy; and patient selection for medical management. 3 figures. 21 references.

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Evaluation of Benign Prostatic Hyperplasia Treatments: How Can We Improve the Outcome Measure and Success Criteria? Source: European Urology. 32(Supplement 2): 38-41. July 1997. Contact: Available from S. Karger Publishers, Inc. 26 West Avon Road, P.O. Box 529, Farmington, CT 06085. Summary: This article considers the evaluation of treatments for benign prostatic hyperplasia (BPH), a situation that is complicated by a number of interdependent factors. The evaluation of the individual patient is influenced by the risk-to-benefit ratio and health-related quality of life (QOL); and this, in turn, is interrelated with the evaluation of therapeutic options. Current outcome measures include subjective measurements (symptom scores and patient reports) and objective measurements (uroflow and prostate volume). In order to improve outcome measures it is important to use health-related QOL scales and symptom and bother-associated (level of annoyance) scores. In addition, the patient should complete frequency and volume charts and possibly use home flowmetry; transitional zone measurements may also play a role in finding a better treatment strategy. It is important to consider the adverse effects and complication rates of invasive and pharmacological treatments (including their influence on QOL) and economic factors such as the cost of treatment, the cost of following guidelines, and the durability and failure rate associated with treatment. The author concludes that, in order to manage the increasing number of BPH patients who seek care effectively, it is important to share care provision between urologists and general practitioners, but this will require improved guidelines, better data, and better outcome measurements. 1 table. 12 references. (AA-M).

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Benign Prostatic Hyperplasia: Natural Evolution Versus Medical Treatment Source: European Urology. 32(Supplement 2): 34-37. July 1997. Contact: Available from S. Karger Publishers, Inc. 26 West Avon Road, P.O. Box 529, Farmington, CT 06085. Summary: This article considers the topic of natural evolution versus medical treatment for benign prostatic hyperplasia (BPH). The author stresses that the epidemiology and natural evolution of the condition must be taken into consideration. The incidence of BPH increases with age; it is thought that about 75 percent of men over 50 years of age suffer from some symptoms commonly associated with BPH. There are also differences in the incidence of BPH among various racial and ethnic groups. For example, it is considerably less common among Japanese men compared with Caucasian men. Evidence from prospective studies, retrospective studies, and the placebo arms of randomized, controlled studies regarding the natural evolution of BPH suggests that a strategy of 'watchful waiting' may be considered as a treatment option, since the majority of patients do not show a worsening of symptoms over time. However, the chance for improvement of symptoms and the degree of symptom improvement has been shown to be higher with alpha1-blocker therapy than with 'watchful waiting.' As both symptoms and treatment have an impact on the patient's quality of life, there is now a strong case for involving the patient in making quality of life decisions based on his own preferences and attitudes. 2 figures. 2 tables. 14 references. (AA-M).

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Long-Term Evaluation of Tamsulosin in Benign Prostatic Hyperplasia: PlaceboControlled, Double-Blind Extension of Phase III Trial Source: Urology. 51(6): 901-906. 1998. Contact: Available from Urology. P.O. Box 2126, Marion, OH 43306-8226. (800) 215-4692. Fax (740) 382-5866. Summary: This article describes a study that evaluated the long term efficacy and safety of once daily tamsulosin at 0.4 or 0.8 milligrams (mg), a unique selective alpha1Aadrenoceptor antagonist, in patients with benign prostatic hyperplasia (BPH). The study extended a 13 week, Phase III multicenter placebo controlled, double blind outpatient trial for an additional 40 weeks. Of 618 patients, 418 continued into the extension phase on the same double blind medication and dose. The primary efficacy parameters were total American Urological Association (AUA) symptom score and maximum urinary flow (Qmax). The mean changes in AUA symptom score from baseline to end point were statistically significant in all groups. Significant improvements were observed for both tamsulosin groups but not for the placebo group. The statistically significant improvements from baseline in efficacy parameters observed for each tamsulosin group at the end of the 13 week Phase III trial were maintained during the long term extension phase. Tamsulosin at both dosages was well tolerated as maintenance therapy. Clinically significant orthostatic hypotension (low blood pressure) was not observed. Vital sign changes in either hypertensive or normotensive patients were not clinically significantly different across the three groups. The authors conclude that tamsulosin once daily at 0.4 or 0.8 mg was shown to be effective, safe, and well tolerated in the target BPH population during long term use. 1 appendix. 2 figures. 2 tables. 11 references.

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New Use for Alpha Blockers: Benign Prostatic Hyperplasia Source: American Family Physician. 49(8): 1885-1888. June 1994.

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Summary: This article describes treatment with alpha1-adrenergic blockers as a reasonable alternative to surgery for patients with symptomatic benign prostatic hyperplasia (BPH). The author notes that alpha blockers may also be useful as an adjunct to finasteride in the treatment of this disorder. Topics include the drugs' mechanism of action; pharmacokinetics; efficacy; adverse effects; drug interactions; indications; clinical presentation; and treatment. The author stresses that pretreatment evaluation is essential to ensure that the patient does not have an infection, prostate cancer, or another serious cause of the prostatic symptoms. Side effects can be minimized by administering the medication at night and reversed by discontinuing the drug. In more than 50 percent of patients, treatment with alpha blockers results in objective and subjective symptomatic relief. 1 table. 13 references. (AA-M). •

Treatment for Benign Prostatic Hyperplasia Among Community Dwelling Men: The Olmsted County Study of Urinary Symptoms and Health Status Source: Journal of Urology. 162(4): 1301-1306. October 1999. Contact: Available from Lippincott Williams and Wilkins. 12107 Insurance Way, Hagerstown, MD 21740. (800) 638-3030 or (301) 714-2334. Fax (301) 824-7290. Summary: This article describes treatments for benign prostatic hyperplasia (BPH) among men participating in the Olmsted County study of urinary symptoms and health status among men during 10,000 person-years of followup. A cohort of 2,115 men (40 to 79 years old) was randomly selected from an enumeration of the Olmsted Country, Minnesota, population (55 percent response rate). Participants completed a previously validated baseline questionnaire to assess symptom severity and voided into a portable urometer. A 25 percent random subsample underwent transrectal sonographic imaging of the prostate to determine prostate volume and measurement of serum prostate specific antigen (PSA). Followup included retrospective review of community medical records and completion of a biennial questionnaire to determine the occurrence of medical and surgical treatment for BPH in the subsequent 6 years. During more than 10,000 person-years of followup, 167 men were treated, yielding an overall incidence of 16.0 per 1,000 person-years. There was a strong age related increase in risk of any treatment from 3.3 per 1,000 person-years for men 40 to 49 years old, to more than 30 per 1,000 person-years for those men 70 years old or older. Men with moderate to severe symptoms, depressed peak urinary flow rates, enlarged prostate, or elevated serum PSA had about 4 times the risk of BPH treatment as those who did not. The authors conclude that the data demonstrate that treatment for BPH is common in elderly men with nearly 1 in 4 receiving treatment in the eighth decade of life (the authors note that repeat contact and availability of urological measurements during the study period may have influenced treatment decisions in this cohort). Furthermore, the data suggest that men with moderate to severe lower urinary tract symptoms, impaired flow rates, or enlarged prostates are more likely to undergo treatment, with increases in risk of similar magnitude to those associated with adverse outcomes, such as acute urinary retention. 3 tables. 1 figure. 37 references.

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Diagnosis and Treatment of Benign Prostatic Hyperplasia Source: Hospital Medicine. 28(2): 117-118, 120-124. February 1992. Summary: This article discusses benign prostatic hyperplasia (BPH), enlargement of the prostate gland due to an increased number of stromal cells. Topics include its etiology, natural history, clinical manifestation, laboratory findings, cystourethroscopy, imaging modalities used in diagnosis, urodynamic evaluation, differential diagnosis, and

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surgical, pharmaceutical, and mechanical treatments for the condition. The authors also list the general indications for the relief of prostatic obstruction from BPH. 3 figures. 2 tables. 5 references. •

Benign Prostatic Hyperplasia: Antecedents and Natural History Source: Epidemiologic Reviews. Volume 14. 1992. p. 131-153. Summary: This article discusses the antecedents and natural history of benign prostatic hyperplasia (BPH). The authors first review prostate anatomy as it relates to the pathologic process by which BPH develops. They summarize epidemiologic and biologic evidence concerning predisposing factors, and finally review the natural history of the untreated disease and its complications. The authors emphasize the disease itself, with only a brief mention of treatment outcomes. One section considers prostate cancer risk among men with BPH. 3 figures. 1 table. 185 references.

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Local Microwave Hyperthermia of Benign Prostatic Hyperplasia (BPH) Source: Journal of Urologic Nursing. 11(1): 24-30. January-March 1992. Summary: This article discusses the use of local microwave hyperthermia to treat benign prostatic hyperplasia (BPH). The author discusses several methodologies of local hyperthermia of the prostate that have been developed and tested in clinical trials on the treatment of BPH. Topics covered include transrectal hyperthermia, transurethral hyperthermia, the equipment and supplies used for each, patient selection, and a brief review of the international experiences with hyperthermia treatment of BPH. The author concludes that hyperthermia for BPH cannot achieve the same results as surgical procedures, as measured by urodynamic and subjective voiding parameters. 2 figures. 1 table. 13 references.

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Updated Patient Information for Treatment of Benign Prostatic Hyperplasia: A Permanent Challenge Source: European Urology. 32(Supplement 2): 42-44. July 1997. Contact: Available from S. Karger Publishers, Inc. 26 West Avon Road, P.O. Box 529, Farmington, CT 06085. Summary: This article discusses the use of patient education and information provision as a crucial part in the decision-making process for treating benign prostatic hyperplasia (BPH). The author states that, ideally, a decision analysis should be performed in order to provide patient information and enhance decision-making procedures in BPH. The steps associated with a decision analysis include creating a decision tree, identifying decision alternatives, quantifying the potential outcomes, and weighing the potential outcomes according to the patients' requirements. However, doctors have their own individual experience and information on treatment from a wide variety of sources, e.g., journals, conferences, and industry. Patients, in contrast, are typically informed by the popular media, friends, and relatives. Updated patient information for the treatment of BPH therefore remains a permanent challenge. Each patient also has an individual acceptance level of his symptoms, an individual tolerance for therapy, and an individual approach to medication or surgery. The doctor may have novel experience with new drugs and instrumental procedures and his own individual availability of treatment options. The doctor must always take the cost-effectiveness of a treatment into consideration. 2 tables. 2 references. (AA-M).

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Tamsulosin: A Uroselective Drug in the Management of Benign Prostatic Hyperplasia Source: Today's Therapeutic Trends: The Journal of New Developments in Clinical Medicine. 16(2): 119-137. 2nd Quarter 1998. Contact: Available from Communications Media for Education, Inc. Post Office Box 712, Princeton Junction, NJ 08550. Summary: This article discusses the use of tamsulosin in the management of benign prostatic hyperplasia (BPH). Tamsulosin (Flomax), the first of a new class of alpha blockers, demonstrates preferential selectivity for the 1A-receptor subtype which predominates in prostatic smooth muscle. Therefore, this agent is optimally effective in treating the symptoms of BPH, while reducing extraprostatic effects and thus the incidence of treatment related adverse reactions. These adverse reactions were more often encountered with the use of earlier alph-receptor antagonists. Overall, tamsulosin has a number of significant advantages. Its long duration of action allows for once a day dosing within a range of 0.4 to 0.8 mg. Its therapeutic effect, as indicated by a more than 30 percent increase in peak urinary flow rate, is achieved in over 50 percent of patients receiving tamsulosin therapy. Moreover, the therapeutic effect of tamsulosin is realized as early as 2 to 3 weeks after reaching the optimum dosage. In addition to controlling the irritative symptoms of BPH, tamsulosin dosage can be titrated to achieve the desired reduction in obstructive urinary tract symptoms, such as a weak urinary stream, hesitancy, straining, and incomplete voiding. If necessary, the dose can also be decreased to reduce the incidence of any untoward side effects. The occurrence of cardiovascular system effects that may be seen with earlier alph blocking agents is less of a concern due to tamsulosin's demonstrable uroselective activity. Finally, as any pharmacotherapy for BPH must be administered indefinitely to maintain the desired therapeutic effect, the favorable long term clinical experience with tamsulosin treatment is particularly significant. 2 tables. 95 references.

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Operative Procedures for Benign Prostatic Hypertrophy Source: Nursing Times. 91(38): 34-35. September 20, 1995. Summary: This article examines the clinical management of an enlarged prostate. Topics include preoperative care; the operating procedure (prostatectomy); postoperative care and complications; the anatomy and physiology of the prostate and surrounding structures; signs and symptoms of benign prostatic enlargement; and pain control. The author concludes that, even though clinical trials comparing medical treatment and new surgical techniques flourish, open prostatectomy or transurethral resection (TURP) remain the treatments of choice. 1 figure. 10 references. (AA-M).

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Thermotherapy: A New Treatment for BPH (Enlarged Prostate) Source: Family Urology. p. 12-13. Summer 1996. Contact: Available from American Foundation for Urologic Diseases, Inc. 300 West Pratt Street, Suite 401, Baltimore, MD 21201. (410) 727-2908. Summary: This article explains the technique of thermotherapy for patients with benign prostatic hyperplasia (BPH). This nonsurgical treatment has provided relief of urinary problems for over 35,000 men worldwide, and due to recent U.S. Food and Drug Administration (FDA) approval, is now available in the United States. The author briefly reviews the condition of BPH, including its diagnosis. Treatment options are then outlined, including watchful waiting, drug therapy, surgery, and thermotherapy (also known as transurethral microwave thermotherapy or TUMT). Thermotherapy is the use

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of controlled heat at high temperatures to safely destroy the excess prostatic tissue which can cause the symptoms of BPH. Heat is delivered to the prostate by using a small microwave treatment catheter that is inserted into the urethra. The inclusion of a cooling system in the microwave applicator allows for deeper penetration of the power, while eliminating local pain and urethral destruction. Because the urethra is constantly cooled and protected, the treatment is anesthesia free, is performed on an outpatient basis, and does not have the side effects associated with other treatments. The benefit of the treatment begins to be felt 6 to 8 weeks following the procedure. This gradual improvement is due to the steady absorption by the body of treated prostate tissue. One sidebar describes the technique of watchful waiting as a treatment option for prostate cancer. 1 figure. (AA-M). •

Managing Benign Prostatic Hyperplasia Source: American Family Physician. 66(1): 77-84; 87-88. July 1, 2002. Contact: Available from American Academy of Family Physicians. 8880 Ward Parkway, Kansas City, MO 64114-2797. (800) 274-2237. Summary: This article outlines the medical and surgical options used for the treatment of benign prostatic hyperplasia (BPH), options which have expanded in recent years. Saw palmetto, the most widely used complementary medication, is less effective than standard medical therapy but has fewer side effects. Although nonselective alpha blockers provide rapid relief of symptoms and are relatively inexpensive, they can cause dizziness and orthostatic hypotension. These effects occur less often with tamsulosin, a more selective alpha blocker. Finasteride, a 5 alpha-reductase inhibitor, slowly reduces prostatic volume but is not as effective as alpha blockers, especially in men with a smaller prostate. Dutasteride, a new 5 alpha-reductase inhibitor, has recently been labeled for the treatment of BPH. Surgery may be appropriate initial treatment in patients with severe symptoms who are not at high risk for complications. Surgery may also be indicated in patients who have failed medical therapy or have recurrent infection, hematuria (blood in the urine), or renal (kidney) insufficiency. Transurethral resection of the prostate (TURP) is effective in most patients, but it carries some risk of sexual dysfunction, incontinence, and bleeding. Surgical procedures that use thermal microwave or laser energy to reduce hyperplastic prostate tissue have recently become available. In general, the newer procedures are less expensive than transurethral resection of the prostate and have fewer complications; however, the need for retreatment is somewhat greater with these less invasive techniques. 1 figure. 2 tables. 29 references.

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Benign Prostatic Hyperplasia: Diagnosis and Treatment Guideline Overview Source: Journal of the National Medical Association. 86(7): 489, 548-549. Summary: This article presents an overview of the diagnosis and treatment of benign prostatic hyperplasia (BPH). The article describes how the Agency for Health Care Policy and Research (AHCPR) developed the clinical practice guideline. It then outlines the findings and recommendations established by the AHCPR panel. The article lists recommendations regarding diagnosis, including diagnostic testing, and five treatments: watchful waiting, alpha-blocker drugs, finasteride (Proscar), balloon dilation, and surgery treatment. The article also lists three publications that present the guideline information in several forms. One sidebar summarizes key points about BPH for health care providers and patients.

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Benign Prostatic Hyperplasia: Challenges for the New Millennium Source: Current Opinion in Urology. 10(4): 301-306. July 2000. Contact: Available from Lippincott Williams and Wilkins. 241 Borough High Street, London, SE1 1GB, UK. +44 (0) 171940-7500. E-mail: [email protected]. Summary: This article provides information on the epidemiology, etiology, classification, pathophysiology, symptoms, diagnosis, and treatment of benign prostatic hyperplasia (BPH). The understanding and therapy of BPH has become more complex recently. The molecular mechanisms and growth factors involved in BPH need to be elucidated in the new millennium. The current classification of disease reflects the varied pathophysiologic mechanisms causing lower urinary tract symptoms (LUTS). In addition, symptom scores have improved evaluation of men with BPH, yet bothersomeness' and health related quality of life' should be better recognized as significant outcome parameters. Clinical evaluation with laboratory markers specific for BPH or LUTS is currently inadequate. Yet, urodynamic evaluation should remain an important aspect of evaluation to guide selection of therapy. Recently, medical therapy has expanded to include uroselective alpha blockade and phytotherapy, yet more research is needed. The most significant growth field, however, is in minimally invasive therapies of the prostate. Long term comparative prospective multicenter studies are needed to properly evaluate the outcomes of new technologies compared to traditional procedures that are considered standard of care. 32 references.

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Comparison of Transurethral Surgery with Watchful Waiting for Moderate Symptoms of Benign Prostatic Hyperplasia Source: New England Journal of Medicine. 332(2): 75-79. January 12, 1995. Summary: This article reports on a multicenter randomized trial that compared transurethral resection of the prostate (TURP) with watchful waiting in men with moderate symptoms of benign prostatic hyperplasia (BPH). Of 800 men over the age of 54 years who were screened between July 1986 and July 1989, 556 were studied (280 in the surgery group and 276 in the watchful-waiting group). Patients' symptoms and the degree to which they were bothered by urinary difficulties were measured with standardized questionnaires and medical evaluations; treatment failure was the primary outcome measure. The researchers conclude that, for men with moderate symptoms of BPH, surgery is more effective than watchful waiting in reducing the rate of treatment failure and improving genitourinary symptoms. Watchful waiting is usually a safe alternative for men who are less bothered by urinary difficulty or who wish to delay surgery. 1 figure. 3 tables. 15 references. (AA-M).

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Treatment of Benign Prostatic Hypertrophy with Opuntia Ficus-Indica (L.) Miller Source: Journal of Herbs, Spices and Medicinal Plants. 2(1): 45-49. 1993. Contact: Available from Haworth Press. 10 Alice Street, Binghamton, NY 13904. (800) 342-9678. Summary: This article reports on a preliminary evaluation of the potential clinical application of Opuntia flowers in the treatment of benign prostatic hyperplasia (BPH). Opuntia ficus-indica, commonly known as the Indian-fig prickly pear, subjectively improved the discomforts associated with BPH. The effectiveness of the dried flowers for treatment of BPH was evaluated in 2 clinical trials: 58 patients at a private clinic and 30 patients that visited a medical center's urology outpatient clinic. In both trials, patients reported improvement in the symptoms of BPH following treatment with

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Opuntia. The authors are presently conducting a double-blind crossover, placebocontrolled trial with 100 patients, to last 8 to 12 months. 1 table. 9 references. •

Effects of a Saw Palmetto Herbal Blend in Men with Symptomatic Benign Prostatic Hyperplasia Source: Journal of Urology. 163(5): 1451-1456. May 2000. Contact: Available from Lippincott Williams and Wilkins. 12107 Insurance Way, Hagerstown, MD 21740. (800) 638-3030 or (301) 714-2334. Fax (301) 824-7290. Summary: This article reports on a randomized, placebo controlled trial that tested the effects of a saw palmetto herbal blend in men with symptomatic benign prostatic hyperplasia (BPH). The authors randomized 44 men aged 45 to 80 years old with symptomatic BPH into a trial of a saw palmetto herbal blend versus placebo. Results showed both saw palmetto herbal blend and placebo groups had improved clinical parameters with a slight advantage in the saw palmetto group (not statistically significant). Neither prostate specific antigen (PSA) nor prostate volume changed from baseline. Prostate epithelial contraction was noted, especially in the transition zone, where percent epithelium decreased from 17.8 percent at baseline to 10.7 percent after 6 months of saw palmetto herbal blend. Histological studies showed that the percent of atrophic glands increased from 25.2 percent to 40.9 percent after treatment with saw palmetto herbal blend. The mechanism of action appeared to be nonhormonal, but it was not identified by tissue studies of apotosis, cellular proliferation, angiogenesis, growth factors, or androgen receptor expression. The authors noted no adverse effects of saw palmetto herbal blend. When the study was no longer blinded, 41 men elected to continue therapy in an open label extension. The authors conclude that saw palmetto herbal blend appears to be a safe, highly desirable option for men with moderately symptomatic BPH. Saw palmetto herbal blend therapy was associated with epithelial contraction, especially in the transition zone, indicating a possible mechanism of action underlying the clinical significance detected in other studies. 2 appendices. 4 figures. 4 tables. 23 references.

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Comparison of Techniques for Eliciting Patient Preferences in Patients with Benign Prostatic Hyperplasia Source: Journal of Urology. 168(7): 155-159. July 2002. Contact: Available from Lippincott Williams and Wilkins. 12107 Insurance Way, Hagerstown, MD 21740. (800) 638-3030 or (301) 714-2334. Fax (301) 824-7290. Summary: This article reports on a study in which the authors compared the Health Utility Index (HUI), EuroQol (EQ-5D), and time trade-off methods to identify the most suitable technique for collecting preference data in a clinical trial of patients with benign prostatic hyperplasia (BPH). In the study, a total of 29 men with symptomatic BPH were interviewed by a single trained interviewer who collected demographic data and administered EQ-5D and time trade-off questionnaires. Participants self administered the other tests. Although mean utility values for HUI, EQ-5D, and 1 year time trade-off were similar, only utility values elicited using time trade-off with a 1 year time frame significantly correlated with symptom scores. All participants indicated that the HUI and EQ-5D were appropriate for assessing BPH, while approximately 10 percent considered time trade-off questions irrelevant. Average completion time for the HUI, time trade-off, and EQ-5D was 31, 25, and 10 minutes, respectively. 1 figure. 2 tables. 16 references.

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Prevalence and Bothersomeness of Lower Urinary Tract Symptoms in Benign Prostatic Hyperplasia and Their Impact on Well-Being Source: Journal of Urology. 166(2): 563-568. August 2001. Contact: Available from Lippincott Williams and Wilkins. 12107 Insurance Way, Hagerstown, MD 21740. (800) 638-3030 or (301) 714-2334. Fax: (301) 824-7290. Website: www.lippincott.com. Summary: This article reports on a study that established the prevalence and bothersomeness of symptoms and their impact on well being in a large group of strictly selected men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia (BPH). Included in the study were 475 consecutive men who met the criteria of the International Consensus Committee on BPH and who voided more than 150 milliliters during uroflowmetry. International Prostate Symptom Scores (IPSS) and quality of life score were determined. The symptoms with the highest prevalence were weak urinary stream, frequency and urgency. Urgency, nocturia (urinating at night), and hesitancy were the most bothersome symptoms. Patients were only discouraged from performing normal daily activity when the symptom index exceeded 20. Incomplete emptying and frequency bothersomeness correlated strongly, and weak urinary stream and hesitancy bothersomeness correlated weakly with all health and quality of life domains. 3 figures. 4 tables. 18 references.

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Doxazosin for Benign Prostatic Hyperplasia: Long-Term Efficacy and Safety in Hypertensive and Normotensive Patients Source: Journal of Urology. 157(2): 525-530. February 1997. Summary: This article reports on a study to evaluate the sustained efficacy and safety of doxazosin for longterm treatment (up to 48 months) of normotensive and hypertensive patients with benign prostatic hyperplasia (BPH). A total of 272 normotensive and 178 mildly to moderately hypertensive men entered a longterm extension study of doxazosin therapy (1 to 8 and 1 to 12 mg. 1 time daily, respectively) for BPH following participation in double-blind, placebo controlled studies. The starting dose of doxazosin was 1 mg. with upward titrations at 2-week intervals to a stable, efficacious and welltolerated dose. At the time of data analysis, patients had received between 1 and 48 months of stable dose doxazosin therapy. At the end point analysis, doxazosin treatment resulted in significant increases above baseline in maximum and average urinary flow rates. As assessed by the patient, total, obstructive, and irritative BPH symptoms also improved significantly with doxazosin treatment. Sustained blood pressure decreases with doxazosin were statistically and clinically significant in hypertensive patients. Blood pressure decreases in normotensive patients were not clinically significant. Changes in heart rate were not significant. Doxazosin was well tolerated with almost 90 percent of adverse experiences considered mild or moderate in severity. The most common adverse events were dizziness, headache, and fatigue in normotensive and hypertensive patients. 4 figures. 6 tables. 27 references. (AA-M).

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Comparison of the Efficacy and Safety of Finasteride in Older Versus Younger Men with Benign Prostatic Hyperplasia Source: Urology. 57(6): 1073-1077. June 2001. Contact: Available from Urology. P.O. Box 2126, Marion, OH 43306-8226. (800) 215-4692. Fax (740) 382-5866.

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Summary: This article reports on a study undertaken to compare the efficacy and safety of finasteride (5 milligrams) in older (65 years old or older) versus younger (45 to younger than 65 years old) men with benign prostatic hyperplasia (BPH). The Proscar Long Term Efficacy and Safety Study (PLESS) was a 4 year, randomized, double blind, placebo controlled trial assessing the safety and efficacy of finasteride 5 milligrams in 3,040 men aged 45 to 78 years old with symptomatic BPH, enlarged prostates, and no evidence of prostate cancer. The endpoints included urinary symptoms, prostate volume, occurrence of acute urinary retention, or BPH related surgery, and safety. In both age groups, finasteride treatment led to a 51 percent reduction in the relative risk for acute urinary retention (inability to urinate because of blockage) or BPH related surgery, a significant and durable improvement in symptoms score, and a significant and sustained reduction in prostate volume. Within each age cohort, no significant differences were found between the placebo and finasteride treated patients in the incidence of cardiovascular adverse events. Significant differences were evident between the placebo and finasteride groups in the incidence of the typical, known, drug related adverse events, but no specific differences were associated with age. No drug interactions of clinical importance were observed in the finasteride treated patients. The results demonstrate that finasteride is highly effective in improving symptoms and reducing prostate volume in many men and in reducing the risk of acute urinary retention and BPH related surgery. 2 figures. 3 tables. 16 references. •

Practice Trends in the Diagnosis and Management of Benign Prostatic Hyperplasia in the United States Source: Journal of Urology. 154(1): 205-206. July 1995. Contact: Available from Williams and Wilkins. 351 West Camden Street, Baltimore, MD 21201-2436. (800) 638-6423; in Maryland (800) 638-4007. Summary: This article reports on a survey designed to ascertain practice trends in the diagnosis and management of benign prostatic hyperplasia (BPH) in the United States. In August 1994, a random sample of 514 American urologists was surveyed by the Gallup Organization regarding practice patterns for BPH. The survey revealed that 99 percent of the respondents were aware of and used the American Urological Association (AUA) symptom score index, and that 21 percent of these respondents had altered their diagnosis and management strategies because of its existence. The authors conclude that therapeutic recommendations of the respondents based upon AUA symptom score index severity parallel the recently announced Federal Agency for Health Care Policy and Research BPH guidelines. 3 tables. 3 references.

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Water-Induced Thermotherapy for Benign Prostatic Hyperplasia Source: Techniques in Urology. 6(4): 294-299. December 2000. Contact: Available from Raven Press, Ltd. 1185 Avenue of the Americas, New York, NY 10036. (800) 777-2836 or (212) 930-9500. Summary: This article reports on water induced thermotherapy (WIT), administered by the Thermoflex System, a new, minimally invasive technique for the treatment of benign prostatic hyperplasia (BPH). The Thermoflex System consists of an extracorporeal (outside the body) heat source and a proprietary closed loop catheter system. Water, heated to 60 degrees Centigrade, is continuously circulated through the catheter to a treatment balloon, which conducts thermal energy to targeted prostatic tissue. The combination of heat and compression reduces the heat sink effect of the circulating blood, thus enhancing the thermal energy transfer to the compressed tissue.

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Benign Prostatic Hyperplasia

WIT treatment is performed using only topical urethral anesthetic, in a single 45 minute session. The 2 year follow up data from a European multicenter study consisting of 125 patients showed an improvement in peak urine flow of 87.4 percent from baseline and in the International Prostate Symptom Score (IPSS). Patient tolerance of WIT was rated as excellent or good in 91.8 percent of the procedures. The authors conclude that WIT is effective, simple, and inexpensive; has few side effects; and does not need special probes to monitor prostate or rectum temperature; thus, it can be used in hospitals, outpatient clinics, and doctors' offices. 7 figures. 1 table. 10 references. •

Transurethral Microwave Thermotherapy: Refining Treatment Strategy for Benign Prostatic Hyperplasia Source: Current Opinion in Urology. 6(1): 14-19. January 1996. Contact: Available from Rapid Science Publishers. 400 Market Street, Suite 750, Philadelphia, PA 19106. (800) 552-5866 or (215) 574-2210. Fax (215) 574-3533. Summary: This article reviews recent advances in transurethral microwave thermotherapy (TUMT), a promising, minimally invasive treatment for patients with complaints related to benign prostatic hyperplasia (BPH). The results of phase II studies and placebo control studies suggest real therapeutic benefit for certain patient groups who undergo this treatment. A number of reports have appeared that confirm the thermotherapy principle, add to the knowledge of patient selection, and provide data to suggest that the treatment is durable. Consistently, TUMT appears to be a remarkably safe procedure, and refinement in patient selection will confirm a place for this treatment between medical and surgical alternatives for BPH. The single session, outpatient office-based procedure, which does not require general anesthesia, continues to be an attractive alternative for patients with symptoms of moderate to moderately severe BPH. 1 figure. 4 tables. 23 abstracts. (AA-M).

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Benign Prostatic Hyperplasia (BPH): Development, Diagnosis and Management with the Alpha 1 Blocker, Terazosin Source: Todays Therapeutic Trends: The Journal of New Developments in Clinical Medicine. 2(3): 121-134. 4th Quarter 1993. Summary: This article reviews the condition of benign prostatic hyperplasia (BPH); its development, diagnosis, and treatment with the alpha-1 blocker, terazosin. Topics include normal prostate physiology; the diagnosis of BPH, including symptoms and presentation; and the clinical management of BPH, including animal research studies that led to the use of alpha-1 blockers and the use of terazosin. The authors conclude that terazoxin has proven to be both safe and effective in treating this condition, with a high degree of patient comfort and optimal compliance with daily therapy. 4 figures. 2 tables. 18 references.

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Medical Management of Benign Prostatic Hyperplasia Source: Urologic Nursing. 17(4): 137-141. December 1997. Contact: Available from Society of Urologic Nurses and Associates, Inc. East Holly Avenue, Box 56, Pitman, NJ 08071-0056. (609) 256-2335. E-mail: [email protected]. Summary: This article reviews the medical management of benign prostatic hyperplasia (BPH). The authors review current options for the pharmacologic treatment of BPH, including related nursing management and suggestions for future research in this area of urologic nursing practice. Pharmacologic agents are primarily designed to

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relieve or eliminate the lower urinary tract symptoms (LUTS) caused by prostatic growth and bladder outlet obstruction. They seek to accomplish this by arresting prostatic growth and reducing prostatic size, or by diminishing the smooth muscle tone of the prostatic and proximal urethra. Medical therapy must be limited to those patients who do not have significant obstructive uropathy caused by bladder outlet obstruction. The authors discuss two classes of drugs, the 5 alpha reductase blockers and the adrenergic antagonists, both of which provide acceptable efficacy and tolerable side effects. Although initial clinical experiences favor the efficacy of a combination of alpha reductase blockers and an alpha adrenergic blocking agent over monotherapy, no well controlled clinical trial has been completed to prove or disprove this clinical impression. The authors call for research elucidating the relationship between bladder outlet obstruction and LUTS, and the natural history of BPH, in order to better define the role of medical therapy in controlling or preventing the adverse effects caused by BPH. 2 figures. 14 references. •

Hytrin Treatment of Hypertension and Benign Prostatic Hyperplasia Source: ANNA Journal. American Nephrology Nurses' Association Journal. 22(3): 335336. June 1995. Contact: Available from American Nephrology Nurses' Association. East Holly Avenue, Box 56, Pitman, NJ 08071. (609) 256-2320. Summary: This article reviews the use of Hytrin (terazosin hydrochloride) to treat hypertension and benign prostatic hyperplasia (BPH). The authors present a brief overview of BPH and its diagnosis, then discuss the management considerations for men with BPH. They briefly review the surgical options, then discuss the use of Hytrin. Topics covered include its indications, contraindications, side effects and adverse reactions, and dialyzability. They conclude with a discussion of the nursing implications. They stress that ongoing assessment, observation for side effects, monitoring for lower urinary tract dysfunction, along with patient education and documentation, are the responsibilities of nephrology nurses. 10 references.

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Benign Prostatic Hyperplasia (editorial) Source: Journal of Urology. 153(5): 1540-1542. May 1995. Contact: Available from Williams and Wilkins. 428 East Preston Street, Baltimore, MD 21202. (800) 638-6423. Summary: This article serves as an introduction of sorts to six articles on benign prostatic hyperplasia (BPH) published in the same issue of Journal of Urology. Topics include the natural history and pathophysiology of BPH; the relationship among symptom severity, quality of life, and urodynamic parameters; relieving bladder outlet obstruction; obstruction as a continuous variable, using the parameters of detrusor pressure, peak urinary flow rate, minimum urethral opening pressure, theoretical area of the urethra, and urethral resistance factor; transurethral microwave thermotherapy; laser ablation of BPH; and cost considerations for the various treatment options.

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Prostatism: Benign Prostatic Hyperplasia Source: Urologic Clinics of North America. 23(1): 75-86. February 1996. Contact: Available from W.B. Saunders Company, Periodicals Fulfillment, 6277 Sea Harbor Drive, Orlando, FL 32887. (800) 654-2452.

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Summary: This entry from a monograph on geriatric urology explores the most common cause of outlet obstruction in the male geriatric population, benign prostatic hyperplasia (BPH). The prevalence, pathophysiology, and natural history of BPH are discussed, along with the work-up and indications for medical or surgical intervention. The authors also focus on the medical and surgical options now available for the management of BPH. The options include 5-alpha-reductase inhibitors, other hormonal agents, alpha-adrenergic antagonist drugs, transurethral resection of the prostate (TURP), transurethral incision of the prostate (TUIP), transurethral electrovaporization of the prostate, laser prostatectomy, transurethral balloon dilation of the prostate, prostatic stents, high-intensity focused ultrasound, microwave therapy, transurethral microwave thermotherapy (TUMT), and transurethral needle ablation of the prostate (TUNA). 4 figures. 1 table. 96 references. (AA-M). •

Benign Prostatic Hyperplasia Source: Patient Care. 37(10): 13-14. October 2003. Summary: This entry in a series that quickly outlines patient encounters in the real world of office practice considers a case of benign prostatic hyperplasia (BPH). The article outlines the problem, a 61 year old man who seeks help for progressive urinary symptoms of urgency and frequency. The author then discusses a recommended approach to diagnosis and treatment considerations. One sidebar asks (and answers) two questions that help the reader go through the diagnostic process. 3 figures.

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Saw Palmetto Extracts for Treatment of Benign Prostatic Hyperplasia: A Systematic Review Source: JAMA. Journal of the American Medical Association. 280(18): 1604-1609. November 11, 1998. Summary: This journal article reviews the research on the efficacy and safety of saw palmetto extract (Serenoa repens) in men with symptomatic benign prostatic hyperplasia (BPH). A comprehensive search of the literature identified 18 randomized controlled trials involving 2,393 men who met inclusion criteria. Studies were included if the participants had symptomatic BPH, the intervention was a preparation of Serenoa repens alone or in combination with other phytotherapeutic agents, a control group received a placebo or other pharmacological therapies for BPH, and the treatment duration was at least 30 days. Results from doctor and participant assessments showed that Serenoa repens was superior to a placebo and comparable with finasteride in improving urinary tract symptom scores, nocturia, peak and mean urine flow rates, and residual urine volume. Adverse effects due to Serenoa repens generally were mild and comparable with a placebo. Erectile dysfunction was more common with finasteride (4.9 percent) than with S repens (1.1 percent). The withdrawal rates in men receiving Serenoa repens, a placebo, and finasteride were 9.1 percent, 7 percent, and 11.2 percent, respectively. The authors conclude that Serenoa repens appears to improve urologic symptoms and flow measures in men with BPH; its efficacy is similar to that of finasteride but with fewer adverse effects. The article has 4 figures and 51 references.

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Re: Risk Factors for Benign Prostatic Hypertrophy (editorial) Source: American Journal of Epidemiology. 139(1): 114-115. January 1, 1994. Summary: This letter reports on research in which the authors studied factors associated with benign prostatic hypertrophy (BPH) using the 1986 Barcelona Health Interview Survey, a cross-sectional study of a random sample of the noninstitutionalized

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population of Barcelona. In all, 6,894 people were personally interviewed at their homes; a list of specific self-perceived chronic health problems was part of the interview. Of 1,218 men aged 45 years or more, 98 (8 percent) reported having a prostatic disorder. All males in the same age range who did not report a prostatic disorder were selected as controls (n=1120). In this article, the authors present analyses of the relationship between prostatic disorders and smoking, alcohol consumption, and obesity. They conclude that smoking may be inversely related to BPH, whereas risk estimates for obesity and alcohol are close to the null value. 1 table. 6 references. •

FDA Public Health Notification: Serious Injuries from Microwave Thermotherapy for Benign Prostatic Hyperplasia Source: AUA News. 6(1): 20. January-February 2001. Contact: Available from Lippincott Williams and Wilkins. 351 West Camden Street, Baltimore, MD 21201. (410) 528-4000. Website: lww.com. Summary: This news article offers a Food and Drug Administration (FDA) public health notification on the incidence of serious injuries from microwave thermotherapy for benign prostatic hyperplasia (BPH). The notification also provides information that can help avoid these complications. Although the use of microwave thermotherapy for the treatment of BPH has been demonstrated to be safe and effective, and more than 25,000 procedures have been performed, the FDA is concerned about some unexpected procedure related complications that have occurred since the marketing of these devices. Since 1996, the FDA has received reports of 16 thermal injuries related to microwave thermotherapy. Of these, 10 resulted in fistula (an abnormal passage) formation and 6 resulted in clinically significant tissue damage to the penis or urethra. These injuries may not be apparent at the time of treatment and may take hours or days to develop. The reported injuries have required colostomies, partial amputation of the penis, or other therapeutic interventions. The report outlines the factors that may have contributed to the injuries noted and offers recommendations for preventing those injuries. Continued physician monitoring of the procedure is the most crucial aspect in preventing injuries. Readers are encouraged to copy and distribute this information freely. The FDA medical device postmarket safety notifications can be found on the Internet (www.fda.gov/cdrh/safety.html).

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Enlarged Prostate Source: Mayo Clinic Health Letter. 22(1): 4-5. January 2004. Summary: This newsletter article provides information for men with enlarged prostate (benign prostatic hyperplasia, BPH) whose condition has not responded to the typical medications used. The author reviews other minimally invasive therapies and surgery. Generally, surgery is considered the most effective way to relieve BPH symptoms, but advances in laser treatment have meant faster recoveries and minimal side effects. The article describes transurethral resection of the prostate (TURP), laser therapies, and photoselective vaporization of the prostate (PVP). 2 figures.

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Urodynamic Effects of Various Treatment Modalities for Benign Prostatic Hyperplasia Source: Journal of Urology. 158(6): 2034-2044. December 1997. Summary: This review article covers the effects of various treatments for benign prostatic hyperplasia on urethral resistance. Articles that reported pretreatment and

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posttreatment values of relevant urodynamic parameters were analyzed. Average before and after treatment values of maximum flow rate and detrusor pressure at maximal flow rate for every study were plotted and classified as obstructed, equivocal, or nonobstructed. Average values of maximum flow rate and detrusor pressure at maximal flow rate were calculated for the total number of patients treated by a certain modality. Based on this analysis, the rank order of urodynamic efficacy showed that open prostatectomy is more effective in reducing urethral resistance than is transurethral prostatectomy. These treatments diminish obstruction better than laser treatment or transurethral incision of the prostate, which again are more effective than balloon dilation, alpha-blockers, or transurethral microwave thermotherapy. Finally, androgen deprivation performs better than placebo treatment. The author concludes that the rank order of urodynamic efficacy as determined in this analysis shows a high level of agreement with reported rank order of symptomatic efficacy of various modalities. After placebo treatment there is no significant change in urethral resistance. The author notes that these results indicate that pressure-flow studies are a sensitive way to compare active to placebo treatment and that pressure-flow studies have excellent long-term reproducibility. 7 figures. 4 tables. 85 references. (AA-M). •

Increased Mortality After Transurethral Prostatectomy for Benign Prostatic Hyperplasia Source: Current Opinion in Urology. 2(1): 3-7. February 1992. Summary: Transurethral prostatectomy (TURP) has been associated with a low mortality rate and excellent results in the immediate postoperative period. Recent reports, however, suggest that TURP is associated with a higher long-term mortality and re-operation rate compared with open prostatectomy. This article reviews these recent reports, concluding that a prospective randomized study, comparing immediate and long-term outcomes of TURP, open prostatectomy, and other therapeutic modalities, is necessary. The author provides a flow-chart of a proposed research design. 1 figure. 19 annotated references. (AA-M).

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Benign Prostatic Hyperplasia: Clinical Pearls for Diagnosis and Therapy Source: Consultant. 37(2): 336-338, 341-342, 345. February 1997. Contact: Available from Consultant. Cliggott Publishing Company, 55 Holly Hill Lane, Box 4010, Greenwich, CT 06831-0010. Summary: Voiding dysfunction in men is often caused by benign prostatic hyperplasia (BPH), but the differential diagnosis also includes prostate cancer and nonprostaterelated problems. This article provides guidelines to physicians for the diagnosis and treatment of BPH. A thorough patient history covers not only the classic symptoms, such as decreased force of urinary stream, but also identifies medical conditions that can affect the urinary tract, including diabetes. Readers are advised, when performing the digital rectal examination, to be sure to press into the substance of the prostate; otherwise, areas of induration and nodularity may be missed. Most prostate nodules are not exophytic lumps that project into the lumen of the rectum. Diagnostic tests used include urinalysis; measurement of serum creatinine and prostate-specific antigen (PSA); and transrectal ultrasonography. In selected patients, urodynamics or video urodynamics helps differentiate the various causes of voiding dysfunction. Treatment options discussed for BPH include watchful waiting, androgen deprivation therapy (finasteride), alpha-blockers (terazosin and doxazosin), and surgery. The absolute indications for therapy are deterioration of renal function, hydronephrosis, bladder

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decompensation, acute urinary retention, and life-threatening urinary tract infection. 1 table. 9 references. (AA-M).

Federally Funded Research on Benign Prostatic Hyperplasia The U.S. Government supports a variety of research studies relating to benign prostatic hyperplasia. 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 benign prostatic hyperplasia. 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 benign prostatic hyperplasia. The following is typical of the type of information found when searching the CRISP database for benign prostatic hyperplasia: •

Project Title: ACTION OF HORMONES ON PROTEIN AND RNA METABOLISM Principal Investigator & Institution: Mcphaul, Michael J.; Professor; Internal Medicine; University of Texas Sw Med Ctr/Dallas Dallas, Tx 753909105 Timing: Fiscal Year 2002; Project Start 01-JUN-1976; Project End 30-JUN-2005 Summary: The androgen receptor plays a critical role in the development of the male phenotype and in the regulation of homeostatic processes, such as spermatogenesis. In addition, alteration of androgen receptor function have been implicated in the pathogenesis and progression of a number of disease states, including spinal bulbar muscular atrophy and prostate cancer. A large body of experimental work has defined the functional domains of the androgen receptor and identified a number of structural lesion that contribute to alterations of androgen receptor function. The present application seeks to build upon this foundation to identify the proteins that mediate the function of the androgen receptor in controlling gene expression. Three specific aims are proposed: 1) Extension of prior work that has identified two proteins (RFG/ELE1/ARA70 and 23-3) that interact with the ligand- bound androgen receptor. Experiments are outlined to define the genesis and location of potential isoforms and the roles that each plays in the normal function of the human AR. Experiments to produce and characterize mice with conditional disruptions of the RFG/ELE1/ARA70 gene are proposed. 2) Characterization of proteins that have been identified on the basis of their ability to interact with the androgen receptor protein in two-hybrid screens using the intact AR-A to screen a randomly primed cDNA library. 3) Biochemical characterization of proteins that associate with the androgen receptor using a novel immuno purification method to purify native AR expressed in mammalian cells. Extensions of these studies are proposed to permit an analysis of the effects that thee type of ligand, nature of 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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cell fraction used, and mutations of the AR have on the formation and stability of these complexes. It is anticipated that as a result of these studies a clearer picture will emerge of the proteins that are required for the normal function of the human AR. It is anticipated that this information will have implications for the understanding of androgen resistance syndromes, and for other diseases in which androgens play a pathogenic role, such as benign prostatic hyperplasia and prostate cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: AGING STRUCTURE/FUNCTION

AND

MALE

REPRODUCTIVE

TRACT

Principal Investigator & Institution: Zirkin, Barry R.; Professor; None; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 12-MAY-1994; Project End 31-MAR-2003 Summary: Age-related changes in the male reproductive tract are of importance for a number of reasons, including: 1) the population of the U.S. is aging rapidly; 2) a number of diseases of aged men, such as benign prostatic hyperplasia and prostatic cancer, depend upon testicular hormones; 3) other endocrine diseases, such as osteoporosis, are likely to become major problems in geriatric males; 4) aga-related changes in drug and xenobiotic effects have been shown; and 5) couples are waiting until later in life to have children. The male reproductive tract offers many advantages for studies of age-related phenomena, including: 1) experimental manipulation of the tests/epididymides is unlikely to cause death or morbidity; 2) much is known about the regulation of the male tract; and 3) the male reproductive system is an excellent model for generalized aging because it is possible to study, at once, the influence of age on cells that have different proliferative capacities and are at different stages of differentiation. Thus, there are cells that are proliferating rapidly by mitosis (spermatogonia, prostatic epithelia cells), undergoing meiosis (spermatocytes), permanently postreplicative (Sertoli cells), slowly turning over (Leydig cells), differentiating (spermatids), terminally differentiated (spermatozoa), and exquisitely sensitive to hormones and to changes in testicular function (epididymal and prostatic epithelia cells). In the rat, as in the human, striking changes occur with aging, including reduced secretion of testosterone, diminished germ cell production, reduced numbers of testicular and epididymal sperm, atrophy of the seminiferous epithelium, and increased sensitivity of the prostate gland to androgens. The major objectives of this program project application are to elucidate the critical structural and functional changes associated with aging of Leydig (Drs. Zirkin and Wright, Project 1), prostatic (Dr. Brown, Project 2), Sertoli/germ (Drs. Zirkin and Wright, Project 1), spermatozoal (Dr. Robaire, Project 3) and epididymal (Dr. Robaire, Project 3) cells, and to determine the mechanism by which such changes occur. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: AGING AND PROSTATE GROWTH Principal Investigator & Institution: Dahiya, Rajvir; Professor and Director; Northern California Institute Res & Educ 4150 Clement Street (151-Nc) San Francisco, Ca 941211545 Timing: Fiscal Year 2002; Project Start 01-SEP-1998; Project End 30-NOV-2003 Summary: The main goal of this proposal is to investigate the molecular mechanisms of prostate growth in aging. The rationale for this proposal is that the mechanisms of neoformation of ductal-acinar tissue during the pathogenesis of benign prostatic hyperplasia (BPH) is similar (if not identical) to the process of ductal-acinar growth and

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development occurring during the organogenesis of the prostate in fetal and pubertal periods. This proposal is based on the hypothesis that the age- dependent endocrine control of prostatic cell growth is regulated by mesenchyme-epithelial cell interactions mediated by the local production and action of growth factors (KGF, TGFa, and TGFb). Based upon preliminary experiments, TGFa and KGF may up-regulate and TGFb downregulate the prostatic epithelium growth. This hypothesis will be tested through pursuit of the following specific aims. 1. Analysis of paracrine mechanisms in the regulation of rat fetal prostatic growth and differentiation. Under this specific aim, rat fetal prostates (different ages) will be studied to determine growth kinetics, ductal morphogenesis, expression of differentiation markers and expression of KGF, TGFa and TGFb and their receptors. Specific Aim number 2. Analysis of the growth promoting and morphogenetic effects of rat urogenital sinus mesenchyme (rat UGM) on growth-quiescent adult rat prostatic epithelium. Under this specific aim we will test the hypothesis that rat UGM can induce the growth and differentiation of growth-quiescent adult rat prostatic epithelium. To test this hypothesis, rat UGM will be associated with rat prostatic epithelium from adult rats (age 3, 6, 12, 18 and 24 months) and the resultant tissue recombinants will be grown in kidney capsules of male athymic nude mice and will be characterized for growth, differentiation and expression of KGF, TGFa and TGFb and their receptors. Specific Aim number 3. Analysis of the inter- relationships between growth factor families during normal and impaired prostatic epithelial growth. Under this specific aim, we hypothesize that there is a complex interaction between androgen action and growth factors. Indeed, for some systems it has been shown that the actions of one growth factor may be mediated by other downstream signaling growth factors. To dissect this complex interplay between growth factors, various transgenic knockout mice will be utilized. The goal of this experiment is to elucidate the linkage between different growth factor pathways employing chimeric rat-mouse prostatic tissue recombinants. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: AGING AND PROSTATIC HYPERPLASIA IN TRANSGENIC MICE Principal Investigator & Institution: Chatterjee, Bandana; Professor; Cellular & Structural Biology; University of Texas Hlth Sci Ctr San Ant 7703 Floyd Curl Dr San Antonio, Tx 78229 Timing: Fiscal Year 2003; Project Start 01-SEP-2002; Project End 31-AUG-2006 Summary: (provided by applicant): Age-associated benign prostatic hyperplasia (BPH) is a major health problem of elderly men. The molecular etiology of BPH is complex and not clearly understood. Chronic influence of multiple regulatory factors including androgen and peptide growth factors are suspected to contribute to pro static cell proliferation and pathogenesis. The species-specific nature of BPH and the lack of an appropriate mouse model have impeded progress in the delineation of the causal factors for the development of BPH and testing of potential intervention strategies. It is our hypothesis that prostate-specific overexpression of the androgen receptor (AR) and insulinlike growth factor-1 (IGF- 1) in transgenic mice would cause increased prostatic cell proliferation and would give rise to a pathological condition similar to human BPH. The first specific aim of this proposal is to generate transgenic mice overexpressing AR in the prostate targeted by a ten kilobase pair long homologous mouse probasin gene promoter and to characterize the age-and androgen-dependent changes in the prostatic morphology, cellular composition and gene expression profiles. Region (proximal, intermediate and distal)- and lobe-specific histopathologic changes during aging will be correlated with gene expression profiles determined by micro array analysis. In the

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Benign Prostatic Hyperplasia

second specific aim, we will elucidate the interacting role of AR and IGF-1 in promoting aberrant cell proliferation and gene expression through comparative analysis of monotransgenic mice with individual prostatic overexpression of AR and IGF- 1 and bitransgenic mice with simultaneous overexpression of both AR and IGF- 1 in the prostate. Our preliminary results support the feasibility of the proposed experiments and successful completion of this study is expected to provide important new insights into the cellular and molecular pathways that lead to the development of the prostatic hyperplasia under the influence of physiological stimuli. Additionally, the transgemc model and molecular markers generated through these investigations will be beneficial for future studies concerning the development of effective intervention strategies and progression/remission of the disease process. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ALTERNATE THERAPIES FOR BENIGN PROSTATE SYMPTOMS Principal Investigator & Institution: Dixon, Chistopher M.; Urology; New York University School of Medicine 550 1St Ave New York, Ny 10016 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-MAR-2009 Summary: (provided by applicant): Over the past 10 years, medical therapy for men with symptomatic benign prostatic hyperplasia (BPH) has become first-line therapy. Well-designed clinical trials have defined the role of medical therapy for symptom reduction, improved quality of life and diminished the likelihood of disease progression. Phytotherapy for BPH has long been a popular therapeutic option in spite of the lack of compelling scientific information about the mechanism(s) of action, magnitude of symptom improvement, adverse effects or long-term preventative role of these extracts. The primary objective of this application is to determine whether the long-term use of saw palmetto or pygeum africanum delays or prevents the progression of clinical BPH as compared to placebo. Clinical progression will be specifically defined as symptom progression, acute urinary retention, recurrent infection or urosepsis, urinary incontinence or renal insufficiency. Patients will also be classified if they crossover to other BPH treatment options (watchful waiting, medical or invasive treatment). The secondary research questions include an assessment of the natural history of BPH in a well-defined population, differences over time between the 3 cohorts with respect to symptom score, quality of life, urinary flow rates, post void urinary residual, sexual function and prostate volume. The subgroup hypotheses will assess whether treatment response is related to symptom severity, urinary flow rate, residual urine, prostate size or prostate specific antigen hopefully providing some insight into the mechanism of action should these agents be proven effective. The study will enroll approximately 3000 men at 10 centers during the first 2 years. Patients will be followed at 3-month intervals for 4 to 6 years using standard outcome measures. This trial will determine whether saw palmetto or pygeum africanum are worthwhile alternative for the treatment of men with symptomatic BPH. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ALTERNATIVE THERAPIES FOR BENIGN PROSTATE SYMPTOMS Principal Investigator & Institution: Kreder, Karl J.; Professor; Urology; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-MAR-2009 Summary: (provided by applicant): The long-term objectives and specific aims of this proposal are to establish the University of Iowa Department of Urology and Preventive

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Medicine trials group as a Clinical Evaluation and Treatment Center (CETC) in a multiinstitutional research consortium. The purpose of this consortium is to study the effect of phytotherapy using Sernoa repens (saw palmetto) and Pygeum africanum in men with benign prostatic hyperplasia (BPH). A large segment of the United States population uses phytotherapy for treatment of symptoms of BPH, yet there is little scientific data regarding long-term treatment with these agents. Our proposal here at the CETC will enroll 300 patients in this trial during the enrollment period and follow them for the duration of the trial for a minimum of four years and a maximum of six years. The primary outcome measure will be the clinical progression of BPH. The recruitment, marketing, and retention strategies outlined in the following sections will ensure this level of participation as well as maximize the center's ability to recruit minority populations. This center has all the clinical and laboratory support required as stated in the protocol. The following sections outline innovative methods to recruit a large number of men with BPH as well as multiple strategies to ensure long-term compliance and completion of all scheduled follow-up visits. In summary, this proposal outlines what we believe are the outstanding credentials of the University of Iowa Department of Urology and Preventive Medicine to serve as a Clinical Evaluation and Treatment Center for this multi-institutional clinical trial. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HYPERPLASIA

ALTERNATIVE

THERAPIES

FOR

BENIGN

PROSTATIC

Principal Investigator & Institution: Nickel, J Curtis.; Queen's University at Kingston Kingston K7l 3N6, Canada Kingston, On Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-MAR-2009 Summary: (provided by applicant): Serenoa repens (saw palmetto) and Pygeum africanum appear to have modest benefit on the pathophysiology of established benign prostatic hyperplasia (BPH) but even more importantly these agents may affect the pathogenesis of the progressive disease process. Almost every individual study, systematic review and meta-analysis report analyzing the effect of these phytotherapeutic agents on BPH have come to the same conclusion: further research is needed to determine the long term safety and effectiveness and ability to prevent complications associated with progressive BPH. The primary objective of this study is to determine if serenoa repens or pygeum africanum delays or prevents clinical progression of benign prostatic hyperplasia compared to placebo treatment. Secondary objectives will compare relative efficacy of these two treatments and also determine whether either of these agents ameliorate symptoms of BPH, improve BPH specific quality of life, improve maximum flow rate and reduce residual urine in men with BPH. Men with mild to moderate symptoms of BPH who do not desire or require immediate medical or surgical treatment will be randomized to placebo, serenoa repens or pygeum africanum after placebo run in and will be followed for disease progression for a minimum of four years. Progression will be defined as an increase in AUA symptom score of 4 or more points from baseline, or occurrence of any of the following complications of BPH; acute urinary retention, incontinence, obstructive uropathy (measured as increased creatinine) or BPH related urinary tract infection. The Canadian BPH Research Group (Canadian CETC) have demonstrated experience and expertise in designing and implementing multi-center clinical trials in BPH and are the most successful research group in Canada in recruiting patients to multi-center BPH trials. The principal investigator has been a successful and effective collaborator in studies funded by NIH-NIDDK. The members of this group have demonstrated their

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Benign Prostatic Hyperplasia

willingness and ability to work in an effective and congenial manner in collaborative international multi-center studies including NIH sponsored collaborative groups. The Canadian BPH study group would be a valuable partner in the proposed NIH phytotherapeutic BPH prevention trial. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ALTERNATIVE THERAPIES FOR BENIGN PROSTATIC SYMPTOMS Principal Investigator & Institution: Naslund, Michael J.; Surgery; University of Maryland Balt Prof School Baltimore, Md 21201 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-MAR-2009 Summary: (provided by applicant): The purpose of this request is to establish a cooperative group of approximately 10 prostate evaluation and treatment centers nationwide which will develop and conduct a prospective, randomized, double-blind, placebo controlled clinical trial to determine whether Saw Palmetto(SP) and/or Pygeum Africanum(AP) can prevent the clinical progression of benign prostatic hyperplasia (BPH). BPH is a common disease in men over 50 which can lead to bothersome voiding symptoms, urinary retention, permanent bladder damage, renal failure, urinary tract infections, urosepsis or urinary incontinence. Treatment options with documented efficacy include medication, several thermotherapy options, and surgical prostatectomy. Phytotherapy is another treatment option for BPH which is used widely in Europe and is experiencing increasing utilization in the United States. Two common phytotherapeutic agents SP and PA. Despite the widespread use of these substances, there is no convincing data in the literature which demonstrates efficacy for the treatment of BPH. These phytotherapeutic substances do appear to be safe from the patients' perspective. The objective of this trial is to determine if SP and/or PA can prevent the clinical progression of BPH, as defined by the development of: acute urinary retention, renal insufficiency due to BPH, recurrent urinary tract infections, urinary incontinence, or an increase in the international prostate symptom score (IPSS) of 4 or more points over a four year trial. Parameters to be assessed in the subjects enrolled in this trial include IPSS, peak urinary flow rate, post void residual volumes, quality of life and sexual health questionnaires, prostate size determined by prostatic ultrasound, blood count and blood chemistries, urinalysis, serum hormone levels, a history and physical examination. Patients will be assessed every 3 months over a four year trial period. The chosen group of collaborators will meet to design the protocol including diagnostic criteria, inclusion/exclusion criteria, safety measurements and quality of life outcome measurements. The trial will commence after the protocol has been developed, an operations manual has been completed and data collection techniques have been established. Each site will obtain IRB approval of the final protocol. When the study is complete and the data has been analyzed, publication of relevent results will be done. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ANOIKIS EFFECT BY QUINAZOLINES ON PROSTATE GROWTH Principal Investigator & Institution: Kyprianou, Natasha; James F. Hardymon Chair in Urologic Rese; Surgery; University of Kentucky 109 Kinkead Hall Lexington, Ky 40506 Timing: Fiscal Year 2004; Project Start 01-MAY-2004; Project End 30-APR-2009 Summary: (provided by applicant): Loss of apoptotic control in prostate growth disorders involves the altered expression/activation of downstream intracellular effectors of apoptosis signaling pathways. Re-instating functional apoptotic mechanisms, by targeting specific components in this pathway, are of high significance

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in the regulation of prostate growth. Recent studies documented the ability for quinazoline-based a1-adrenoceptor antagonists, doxazosin and terazosin, to induce apoptosis in human prostate smooth muscle, benign and malignant epithelial cells, via an a1-adrenoceptor independent mechanism and suppress tissue vascularity. Our hypothesis is that quinazoline-based a1-adrenoceptor antagonists suppress prostate growth by inducing apoptosis (via induction of intracellular signaling effectors) and inhibit angiogenesis by promoting anoikis (via interference with extracellular matrix attachments). To test this hypothesis, the following aims are proposed: In Specific Aim 1 we will use DNA microarray analysis and proteomic analysis to identify intracellular signaling effectors of apoptosis induced by quinazoline-based a1-adrenoceptor antagonists in prostate benign and malignant cells. Specific Aim 2 will identify the extracellular matrix components involved in quinazoline-induced anoikis in prostate epithelial and endothelial cells with focus on Fas-Fasligand-caspase-8 activation mechanism and integrin effectors. Specific Aim 3 will establish that the quinazolines, doxazosin and terazosin, suppress prostate vasculature and inhibit tissue angiogenesis in patients after a1 blockade treatment. Immunohistochemical analysis will be performed on tissue specimens from BPH patients treated with a1 blockade (for obstructive symptoms) using antibodies against Factor VIII (microcrossed density), vascular endothelial growth factor (VEGF), and focal ashesion kinase (FAK). The goal of the proposed studies is to determine the early response genes at the intracellular (TGFbeta) and extracellular matrix (integrins) environment underlying the quinazolinemediated apoptosis, targeted by this pharmacologic intervention in benign and malignant prostate growth. Potential results will establish the apoptotic/anoikis effect by the quinazolines as a significant phenomenon with clinical relevance in development and progression of benign prostatic hyperplasia (BPH) prostate cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ANTI-GM1B IGM FOR DETECTION OF LOCALIZED PROSTATE CANCER Principal Investigator & Institution: Ravindranath, Mepur H.; John Wayne Cancer Institute 2200 Santa Monica Blvd Santa Monica, Ca 90404 Timing: Fiscal Year 2004; Project Start 01-APR-2004; Project End 31-MAR-2006 Summary: (provided by applicant): The discovery that tumor cells escape ceramidemediated apoptosis by glycosylating ceramides and storing them as gangliosides (lactosylceramides with sialic acids) suggests that gangliosides (Ggs) may be valuable targets for diagnostic and therapeutic explorations. Stored Ggs are released into the tumor microenvironment and the circulation, where they suppress a variety of cellmediated immune functions. While studying the tumor Ggs shed into the circulation after cryosurgical ablation of liver tumors, we observed that these shed gangliosides induced production of IgM specific to the tumor Ggs. Assay of sera from patients with early-stage sarcoma, colorectal carcinoma and melanoma confirmed the presence of anti-ganglioside IgMs characteristic of early tumors. These novel and serendipitous discoveries led us to evaluate whether specific anti-Gg lgM antibodies could serve as diagnostic and prognostic markers of subclinical prostate cancer (CAP). CaP progresses imperceptibly and is potentially curable when organ-confined. A noninvasive method for early detection would encourage more men to seek chemopreventive treatments before their CaP has metastasized beyond the prostate. Prostate-specific antigen (PSA) is widely used for diagnosing and monitoring CaP. However, serum PSA level does not increase significantly until tumor volume exceeds 1cc, and it is inversely related to a tumor's histologic grade. Moreover, benign prostatic hyperplasia (BPH) and prostatitis

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Benign Prostatic Hyperplasia

can falsely elevate serum PSA. By contrast, serum levels of anti-Gg IgM antibodies in healthy individuals decline with age and remain low (titer <50) above the age of 60. In CaP patients above 60 years of age, serum anti-Gg IgM antibodies, particularly antiGD1a, are highly elevated, possibly due to release and sensitization of tumor Ggs. We have observed that serum IgM antibodies from CaP patients immunostained GM1b more strongly than GD1a, suggesting that GM1b may be more immunogenic in patients. We hypothesize that serum anti-GM1b and anti-GD1a IgM in patients with early-stage CaP (T1c) may represent potential markers for localized disease. Although anti-GM1b is not available from commercial sources, we have identified GM1b in large quantities in CaP cell lines. Therefore we will purify GM1b from CaP lines. We hypothesize that the anti-GM1b and anti-GD1a IgM could be more sensitive prognostic markers in patients with localized disease. We will determine their diagnostic potential with and without serum PSA for identifying patients with stage T1 CaP. 1. To isolate and purify CaPassociated ganglioside GMlb from PC3 and Du145 cell lines, and use this ganglioside to study anti-GM1b IgM antibody titers in sera of patients with localized CaP. 2. To evaluate the diagnostic potential of anti-GM1b and anti-GD1a IgM antibodies, with or without PSA, by assessing sera from patients with stage T1 CaP of various Gleason grades, sera from patients with BPH and prostatitis, and sera from age-matched healthy volunteers. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BIS-PHENOL A: SIGNALING AND MITOGENESIS IN THE PROSTATE Principal Investigator & Institution: Knudsen, Karen E.; Cell Biol, Neurobiol/Anatomy; University of Cincinnati 2624 Clifton Ave Cincinnati, Oh 45221 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007 Summary: (provided by applicant): Environmental and commercially prevalent estrogenic compounds (xenoestrogens) have been classified as endocrine disruptors, or agents capable of disrupting normal hormone function in the human body. Exposure to xenoestrogens has been shown to result in diverse biological outcomes, such as infertility and developmental defects. Although considerable effort has been directed toward delineating the effect of xenoestrogens on the female reproductive system, few studies have examined the effect of such agents on growth and maintenance of the prostate gland. Prostatic epithelia and the cells of primary prostatic adenocarcinomas are dependent on androgen for proliferation and survival. This critical dependence of the prostate on androgen is exploited in the treatment of prostatic proliferative diseases (e.g. benign prostatic hyperplasia and prostatic adenocarcinoma). Increasing evidence also demonstrates a role for estrogen in the prostate cell proliferation. For example, exposure to estrogen has been shown to directly induce prostate hyperplasia animal model systems. Additionally, the anti-estrogen Tamoxifen is used clinically to reduce prostate growth. Despite these observations, the mechanism by which estrogen stimulates prostate cell growth has not been determined. Moreover, the effect of xenoestrogens on prostate proliferation and growth has not been explored. Here we show that the xenoestrogen bis-phenol A (BPA) provides inappropriate mitogenic stimuli to prostatic epithelial cells. This mitogenic activity is associated with nuclear receptor activity, and allows prostate cells to bypass their requirement for androgen. Based on our preliminary data, we hypothesize that BPA activates specific nuclear receptors in prostate cells to propagate inappropriate mitogenic signaling pathways and initiate cellular proliferation. This action of BPA likely facilitates the development of prostate hyperplasias and neoplasias. The experiments outlined herein will determine

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the mechanism by which BPA activates nuclear receptors in prostate epithelia, define the mitogenic signaling pathway for BPA in this cell type, and assess the influence of these agents on the formation and treatment of prostate hyperplasias and neoplasias. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BLADDER OUTLET OBSTRUCTION INDUCED NEUROPLASTICITY Principal Investigator & Institution: Zvara, Peter; Surgery; University of Vermont & St Agric College 340 Waterman Building Burlington, Vt 05405 Timing: Fiscal Year 2002; Project Start 15-AUG-2001; Project End 31-JUL-2004 Summary: (provided by applicant) Benign prostatic hyperplasia (BPH) is the most common cause of bladder outflow obstruction (BOO). This condition is commonly associated with uninhibited urinary bladder contractions. Irritative voiding symptoms, a consequence of uninhibited bladder contractions are very bothersome to a large population of aging men, adversely affecting their quality of life. The overall hypothesis for this research proposal is that the marked changes in the neural control of voiding function that occur following BPH are mediated by multiple factors, including: (1) changes in the properties of urinary bladder afferent neurons induced by peripheral organ (bladder) dysfunction and (2) changes in the properties of interneuronal populations in the spinal cord. Thus, we propose that reorganization of spinal micturition circuitry occurs in response to changes in neural-target organ interactions. We plan to examine the effects of BOO on the neurochemical, organizational and morphological properties of afferent and spinal neurons involved in the micturition reflex pathway. This research proposal aims to provide a more thorough understanding of the wiring diagram for lower urinary tract reflexes and the functions of neurotransmitters in these reflexes. In the first part of our study we will assess neurochemical changes in neurons involved in the micturition reflex that project to the periphery following BOO. Peripheral and spinal neurons projecting to the bladder will be identified following injection of the tracer into the urinary bladder. Subsequently, immunohistochemical techniques will be used to determine changes in the expression of neuroactive compounds in these neurons. A second group of experiments will use pharmacological techniques to evaluate the role of neuroactive compounds in the central micturition pathway following chronic BOO. The effect of selective inhibitors of these neuroactive compounds on the micturition reflexes following BOO and in shamoperated controls will be determined with the use of the cystometrography (recording pressure changes in the urinary bladder during filling and micturition). In the third part of this research project, we propose to determine the organization of urinary bladder interneurons and parasympathetic preganglionic neurons in the. lumbosacral spinal cord. Changes in connectivity between the various spinal elements will be assessed following BOO. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CELL GROWTH INHIBITON AND ESTROGEN ACTION Principal Investigator & Institution: Markaverich, Barry M.; Associate Professor; Molecular and Cellular Biology; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 01-AUG-1983; Project End 31-JUL-2005 Summary: (provided by the applicant) A long-range goal of this research is to define the role of MeHPLA and nuclear type II sites in normal and malignant cell proliferation. The identification of MeHPLA as a ligand for type II sites which controls cell growth led to

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Benign Prostatic Hyperplasia

the development of MeHPLA-related compounds with antiproliferative activities and potential for the treatment of benign prostatic hyperplasia, endometriosis, breast and prostatic cancer. We recently identified the nuclear type II binding site as histone H4. This exciting discovery targets very specific genomic pathways for regulation by MeHPLA and related-compounds including bioflavonoids and phytoestrogens. These compounds bind to type II sites (histone H4) with high affinity and have classically been defined as antioxidants that scavage free radicals. Our recent data indicate very specific regulation of gene transcription at the level of chromatin structure and function by type II site (histone H4) ligands. Histone acetylation is temporally and functionally coupled to DNA replication and gene expression in experimental systems including uterus and cancer cells. We propose that MeHPLA and related compounds control normal and malignant cell proliferation by modulating chromatin acetylation patterns and core nucleosome unwinding by binding to histone H4. We will assess hormonal (estrogen, progesterone) modulation of histone H4 gene expression (mRNA and protein), ligand binding activity and cell proliferation in rat uterus and in ER-dependent (MCF-7 cells) and ER-independent (MDA-MD-231) breast cancer cells in vitro and when grown in nude mice (Specific Aim 1). Potential involvement of histones H1, H2A, H2B and H3 in ligand binding to histone H4 will be studied (Specific Aim 2). The identity of the ligand binding domain(s) on histone H4 by will be determined by protein sequencing and site directed mutagenesis studies (Specific Aim 3). Effects of MeHPLA and related histone H4 ligands on chromatin structure, histone acetylation, and steroid hormone-dependent chromatin remodeling and gene transcription in a cell free system (Specific Aim 4) will be assessed. Estrogen, antiestrogen and MeHPLArelated compound effect on the acetylation of histone H4 (or other histones), specific gene (cyclin Dl and p21) transcription and expression and cell proliferation (cell cycle transcition, etc.) in estrogen-dependent and estrogen-independent breast cancer cells in vitro and in vivo (Specific Aim 5) will be evaluated. The proposed studies should precisely define specific effects of MeHPLA and bioflavonoids on chromatin structure and function, growth related gene transcription and cellular proliferation in normal and malignant cells. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CLINICAL EVALUATION & TREATMENT CENTER FOR BPH Principal Investigator & Institution: Andriole, Gerald L.; Surgery; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-MAR-2009 Summary: (provided by applicant): Lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) are one of the most common disorders of the aging U.S. male. Over the last decade significant advances have been made in characterizing this abnormality and treating it with medical therapy (such as alpha blockers and 5 alpha reductase inhibitors) and minimally invasive surgical techniques (such as stents, lasers, hyperthermia and others). Despite this, use of non-traditional medical therapies for LUTS has greatly increased in recent years. Most trials evaluating these agents are limited by small size, short study interval and absence of standardized testing instruments. For these reasons there is a need to evaluate non-traditional agents such as saw palmetto and pygeum Africanum in a large scale, randomized, placebo-controlled, long-term trial. In this application, we propose one such study, describe our clinical research environment, including patient population, facilities, personnel, experience with prior studies, and other methods to assure recruitment, protocol compliance, and retention for such a study. We describe our willingness to develop a final protocol and collaborate in performing it.

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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CLINICAL TRIAL OF MEDICAL THERAPY IN BENIGN PROSTATIC HYPERPLASIA Principal Investigator & Institution: Ramsdell, Joe W.; University of California San Diego La Jolla, Ca 920930934 Timing: Fiscal Year 2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: COHORT HYPERPLASIA

STUDY

OF

RISKS

FOR

BENIGN

PROSTATIC

Principal Investigator & Institution: Kristal, Alan R.; Member and Associate Head; Fred Hutchinson Cancer Research Center Box 19024, 1100 Fairview Ave N Seattle, Wa 98109 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2006 Summary: (provided by applicant): The overall goal of this application is to understand relationships among hormonal, genetic and behavioral risk factors for symptomatic benign prostatic hyperplasia (BPH). BPH symptoms affect well over half of American men over age 50, with substantial effects on quality of life and medical care cost of over 4 billion dollars annually. This study will assess whether the risk of symptomatic BPH is associated with (1) serum concentrations of steroid hormones and insulin-like growth factors known to affect prostate growth; (2) polymorphisms in genes that affect hormone and growth factor metabolism or activity; and (3) diet and other lifestyle factors that affect steroid hormones and insulin-like growth factor concentration or activity. Data are from the Prostate Cancer Prevention Trial (PCPT), a double blinded, placebo-controlled, randomized trial of the drug finasteride (Proscar) for the primary prevention of prostate cancer. Analyses will be restricted to the approximate 5,000 men in the placebo control group with no medical history or symptoms of BPH at baseline. The primary endpoint, incidence of symptomatic BPH, is based on careful and standardized assessments of lower urinary tract symptoms and treatment for prostate-related disease collected at baseline and annually for 7 years. Steroid hormones, insulin-like growth factor 1 and insulin-like growth factor binding protein 3 will be measured from plasma banked at baseline, and genetic characteristics will be assessed using banked lymphocytes. Diet and other behavioral risk factors were assessed by both interviewer- and selfadministered questionnaires. A nested case-control design, with 700 cases and 700 controls, will be used to address hypotheses related to serum measures and genetic polymorphisms. A cohort study using all 5,000 men will be used to examine hypotheses related to diet and other behavioral risk factors. The nested case-control studies are powered to detect odds ratios of 1.5 and the cohort studies are powered to detect hazard ratios of 1.35, comparing highest to lowest quartiles of exposures, with type I error = 0.05 and type II error = 0.20. This study is highly cost-effective, as all data and samples have been collected, and funds are requested for laboratory analyses of serum and genetic polymorphisms, data preparation, statistical analyses and manuscript preparation. Results from this study will enhance our understanding of the etiology of symptomatic BPH and could potentially be used to develop new strategies for prevention and control of this very common disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Benign Prostatic Hyperplasia

Project Title: CONTROL OF PROSTATE-SPECIFIC GENE EXPRESSION Principal Investigator & Institution: Matusik, Robert J.; Director of Urologic Research; Surgery; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2002; Project Start 30-SEP-1999; Project End 31-MAY-2003 Summary: With the approach of adulthood, the prostate undergoes a developmental change that results in the maturation of that gland at puberty. At this stage, the prostate becomes a differentiated gland which produces proteins fundamental for reproduction and survival of the species. Two recent population trends place the understanding of these processes at the forefront. A decline in male fertility requires a better understanding of normal, reproductive development and an increasing aging population demands a better understanding of the further stages of prostatic growth that often leads to benign prostatic hyperplasia and/or prostate cancer. Androgen plays a key role in the normal development of the prostate however, little is known about the other basic molecular events that are required for organ determination and cell differentiation of the prostate. We have shown that an extremely small probasin promoter fragment contains the necessary regulatory information to target both developmental and prostatic epithelial-specific gene expression to the prostate of transgenic mice. Our hypothesis is that these PB DNA sequences can be used to identify the critical gene regulatory proteins that govern prostatic epithelial cell-specific gene expression. We believe that identifying these critical regulatory proteins which control prostate-specific gene expression will elucidate the mechanisms that control both cell determination and cell differentiation of the prostate. To decipher the information within this PB DNA fragment, the following specific Aims are planned: 1) to characterize the ontogeny of prostate-specific probasin gene expression in the developing mouse UGS; 2) to identify the PB promoter sequences that dictate prostatespecific gene expression; 3) to clone the regulatory factors that interact with the prostatespecific sequences; and 4) to determine the patterns of expression of these prostatespecific factors in the developing mouse. The ultimate goal is to provide a basic understanding of prostatic epithelial cell gene expression that will lead to insight in male infertility and the mechanism that lead to prostatic disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CYCLIN DEPENDENT KINASE INHIBITORS IN BENIGN AND MALIGNANT PROSTATIC DISEASES Principal Investigator & Institution: Cordon-Cardo, Carlos; Director; Sloan-Kettering Institute for Cancer Res New York, Ny 100216007 Timing: Fiscal Year 2002 Summary: The objective of our research focuses on the continued characterization of mutations and altered expression patterns of cyclin-dependent kinase inhibitors (CKI) as they rate to processes of tumorigenesis and tumor progression in prostate cancer. It is our hypothesis that abnormalities of KIP and INK genes, as well as those that affect their encoded products, produce a selective advantage for prostate growth and an aggressive behavior in prostate cancer patients. The Specific Aims are outlined as follows: Aim #1: To determine the frequency and potential clinical relevance of mutations affecting the KIP genes, as well as altered patterns of expression of their encoded proteins, in benign prostatic hyperplasia (BPH) and prostate carcinoma. We have found distinct p27 anomalies in BPH and prostate tumors, supporting the postulate that BPH is not a premalignant lesion. Moreover, prostatic carcinomas displaying a p27 negative phenotype were found to be biologically more aggressive. We plan to validate these

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observations and to study p21 and p57 genes. Aim #2: To define the rate and possible clinical relevance of mutations arising in the INK genes, as well as altered patterns of expression of their encoded products, in BPH and prostatic carcinoma. Preliminary data reveals that altered patterns of p16 expression and methylation of he p16 promoter are frequent events in prostate cancer. We plan to extend and validate these data and to assess the relevance of alterations affecting p18 and p19. Aim #3: To further characterize the histopathology of prostatic tissue in animal models for loss of KIP or INK function, and to produce transgenic models using tissue-specific promoters. We have engineered CKI knockout mice (ie, p27 and Ink4a). p27 mull mice develop hyper-cellular prostatic glands; however,over prostate neoplasms are not observed. Transgenic mice will be generated using cyclins E or each D-type fused to the rat probasin promoter in the presence and absence of either p27 or p16. A model mimicking the human disease is expected. The goal is to translated basic and clinical research findings into clinical studies, and to collaborate with the O'Brien Centers and members of the scientific community, evaluating tumor markers of potential relevance. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DATA COORDINATING CENTER FOR BENIGN PROSTATE SYMPTOMS Principal Investigator & Institution: Lee, Jeannette Y.; Research Professor; Medicine; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-MAR-2009 Summary: (provided by applicant): This proposal is for the Medical Statistics Section (MSS) at the University of Alabama at Birmingham to serve as the Data Coordinating Center (DCC) for the study of alternative therapies in benign prostate symptoms. It is anticipated that 10 Clinical Evaluation and Treatment Centers (CETCs) will enroll approximately 3100 men with benign prostatic hyperplasia (BPH) in a randomized, double-masked, placebo-controlled study of two phytotherapy agents, Serenoa repens (Saw palmetto) and Pygeum africanum in the treatment of BPH. Specific aims of the DCC are to: provide statistical expertise in study design and analyses; provide data management support for the study; develop and maintain a WEB-based system for data transmission and communication from the CETCs to the DCC; establish a Phytotherapy Distribution Center to distribute Saw palmetto, Pygeum africanum and placebo to the CETCs; and provide administrative support for meetings of the Steering and Planning Committee, Executive Committee, Data Safety and Monitoring Board and any subcommittees formed during the progress of the trial. The strengths of the MSS in serving as the DCC are: its well-established infrastructure (personnel, computing facilities, communications networks, and data management system) for providing support to clinical trials; its experience in serving as the coordinating center for NIHsupported multicenter clinical trials groups; and its participation in the UAB Chemoprevention Center. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: DIAGNOSTIC CENTER Principal Investigator & Institution: Lucia, M S.; Pathology; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2001; Project Start 30-SEP-1992; Project End 31-MAR-2005 Summary: This competing renewal application (Diagnostic Center) is for a UO1 grant in response to RFA DK94-18. The investigators describe the widespread economic and

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Benign Prostatic Hyperplasia

medical problems associated with benign prostatic hyperplasia. The overall goal of the study is to test the effectiveness of pharmacological intervention in benign prostatic hyperplasia (BPH) with the hope that pharmacological intervention may prove to be superior to surgery for some patients. The goal of the project under consideration from the University of Colorado is to establish the requested Diagnostic Center for the fullscale trial. The Diagnostic Center will perform assays on peripheral blood with materials sent from several clinical centers; these assays will include prostate specific antigen, luteinizing hormone, testosterone, and dihydrotestosterone. Blood chemistries will be carried out initially and annually for the duration of the trial (described in Appendix F of the protocol). The Diagnostic Center will receive four fixed and two frozen, 18-gauge needle biopsies from each patient entered into the study. A series of slides made from the paraffin-embedded fixed needle biopsies and from the frozen needle biopsies will be examined. These slides will be examined for diagnostic purposes by the principal investigator and an unidentified fellow who will be appointed in the second year of support. Sets of slides will also be made available to the departments of pathology from the hospitals from which the biopsies are obtained. The pathology analyzed in the Diagnostic Center in Denver will be recorded on a standard form that is displayed in the material sent with the application. Additional sections of paraffin-embedded needle biopsies and the remaining materials from frozen needle biopsies will be stored for research in the future. Biopsies will be carried out at the beginning of the study, after one year, and at the end of the study. In addition to the above, immunohistochemical studies will be carried out to assess the expression of prostate specific antigen and the MIB-1 nuclear proliferation antigen. Apoptosis will be evaluated with the TUNEL immunohistochemical technique. Morphometric evaluations will be carried out "using a semiautomated image analysis approach such as that described by Shapiro et al (44)." The step by step methods of staining are listed. The investigators state that conditions stipulated in the pilot study that was carried out in their center made in "impossible.to have any information about the expected ranges of variation for each of the variables with respect to any measures of treatment outcome.From the published literature, however, it is expected that data on 280 patients will be sufficient to produce meaningful results." They state that a ".subset of approximately 280 cases will have detailed analyses performed." Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EFFECTS OF AGING ON PROSTATE STRUCTURE AND FUNCTION Principal Investigator & Institution: Brown, Terry R.; Professor; None; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2003; Project Start 01-MAY-2003; Project End 31-MAR-2008 Summary: (provided by applicant): Aging is a major factor that contributes to abnormal growth of the prostate leading to the condition of benign prostatic hyperplasia (BPH) in men. Unlike the human prostate, the rodent prostate is organized into different anatomical lobes referred to as the ventral, dorsal and lateral. Each lobe is biochemically distinct and differentially responsive to androgens. Based upon embryologic origin and biochemical function, the lateral and dorsal lobes have been considered homologous to the human prostate, whereas the ventral lobe lacks homology. Past studies in our laboratory have established that spontaneous and androgen-stimulated prostate epithelial cell hyperplasia occurs in the dorsal and lateral, but not the ventral lobe of aging Brown Norway rats. Hence, the age-dependent, lobe-specific prostatic hyperplasia of Brown Norway rats is considered to be a model for human BPH. Our working hypothesis is that aging contributes to a progressive increase in oxidative stress within

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the prostate, the consequences of which are alterations in the lobe-specific sensitivity to androgen and alterations in cell regulatory mechanisms. These alterations manifest themselves in the form or reactivated cell proliferation and increased cell survival, with the net effect being cellular hyperplasia. The lobe-specific, age-dependent occurrence of hyperplasia provides a unique model to understand the factors that differentially contribute to hyperplasia. In this application, we propose three aims to determine: 1) if changes in androgen sensitivity alter the expression of cell cycle regulatory molecules that activate cell proliferation leading to hyperplasia; 2) if changes in growth factor regulation and expression increase cell proliferation and survival leading to hyperplasia; and 3) if oxidative stress causes damage to lipids, proteins and DNA that correlates with disruption of normal regulation of prostate growth. These studies should lead to a better understanding of the molecular mechanisms that underlie the incidence of prostatic hyperplasia with increasing age, particularly at a time in life when the androgendependent prostate is exposed to a hormonal milieu with paradoxically diminished testosterone concentration. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EFFECTS OF SAW PALMETTO EXTRACT ON SYMPTOMATIC BENIGN PROSTATIC HYPERPLASIA Principal Investigator & Institution: Hess, David L.; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2002 Summary: Saw palmetto extract (SPE) has seen wide use in Europe for self treatment of benign prostatic hyperplasia (BPH), although the mechanism of action on the human prostate is unknown and efficacy of treatment remains unproven. Suggested mechanisms include inhibition of androgen action and an anti-inflammatory effect. These possibilities were evaluated by study of prostate biopsy specimens obtained before and after treatment with SPE in men during a 6 month randomized clinical trial vs a placebo. Ultrasound-guided sextant biopsies were obtained from 41 men prior to and after 6 months of placebo (n=20) or SPE (n=20) treatment (320 mg/day). The 82 tissue samples were batch processed by routine histology; by morphometry for quantitative tissue composition of the inner and outer gland; by a histopathologic scoring system for acute and chronic inflammation and for atrophy; by immunohistochemical assessment of apoptosis, cell proliferation, and androgen receptor expression; an d by a tissue homogenate assay for androgen levels (expressed as ng/g of prostate tissue). A contraction in the transition zone epithelium from 17.8% before to 10.7% after 6 months of treatment was found in the SPE group (p < 0.01). In a parallel, independent analysis, the epithelial atrophy scores increased from 25.2% before to 40.9% after SPE (p < 0.01). In placebo patients, no significant changes were seen in any tissue measures. None of the other tissue studies revealed any significant changes from baseline during SPE treatment. SPE appears to exert a suppressant effect on the prostatic epithelium, especially the transition zone. Since no alterations in prostatic androgen metabolism or apoptosis markers could be demonstrated, the data suggest that the effect is mediated by a mechanism unrelated to changes in tissue hormone concentrations, receptor expression or to obvious anti-inflammatory effects. How epithelial suppression related to clinical effects, in the absence of pro state volume contraction, is not clear. However, our observation of significant epithelial involution following 6 months of SPE use should encourage further investigation. FUNDING Urological Sciences Research Foundation PUBLICATIONS None PUBLICATIONS None Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: EPIDEMIOLOGY OF UROLOGIC DISORDERS IN MINORITY MEN Principal Investigator & Institution: Mckinlay, John B.; Senior Vice President and Director; New England Research Institutes, Inc. 9 Galen St Watertown, Ma 02472 Timing: Fiscal Year 2002; Project Start 15-JUN-2001; Project End 30-APR-2006 Summary: Urologic disorders, including erectile dysfunction, benign prostatic hyperplasia, prostatis, and hypogonadism, are highly prevalent and have enormous impact on the health, medical-care expenditures, and quality of life of the aging U.S. male population. Surprisingly little is known about the basic epidemiology of these conditions, particularly in minority populations, where they may be especially prevalent. Several professional societies and the NIH have urged that research on urologic disorders in minority men be given highest priority. Similar recommendations regarding erectile dysfunction were made by a 1993 NIH Consensus Conference. The role of health-care access and utilization in relation to the specific conditions is likewise studied. We purpose to conduct a cross-sectional, population-based random- sample survey, building on the field experience of investigators from the Massachusetts Male Aging Study, to examine the epidemiology of urologic disorders in minority men. We will estimate and compare the age-specific prevalence of urologic conditions in Hispanic, black (non- Hispanic), and white (non-Hispanic) men. We will measure the relative contribution of biophysiologic factors, health status, medications and comorbidities, lifestyle and behavioral within each minority group and to variation among the three groups. Medical care access, utilization behavior, and quality of life dimensions will also be explored. Our random sample will include a total of 3000 men aged 40-79 year, 1000 from each of the three above mentioned racial/ethnic groups living in the Boston, MA metropolitan area. We will collect blood samples and comprehensive battery of health information in an in-home interview conducted by bilingual interviewer-phlebotomists. To prepare for the possibility of a future, separately funded prospective study we will actively maintain the sample through regular main contact. This design represents a cost-efficient approach to gathering detailed information on four poorly understood medical conditions in a single wave of field effort. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: TREATMENT

FIBER

TEMPERATURE

SENSOR

FOR

HYPERTHERMIA

Principal Investigator & Institution: Saxena, Indu; Senior Scientist and Group Leader; Intelligent Optical Systems, Inc. 2520 W 237Th St Torrance, Ca 905055217 Timing: Fiscal Year 2002; Project Start 01-APR-1998; Project End 31-AUG-2004 Summary: (provided by applicant): To improve hyperthermia and thermotherapy treatments by providing a realistic, cost effective and efficient technique for temperature profiling in treated tissues, Intelligent Optical Systems proposes to develop an optical fiber temperature (OFT) probe providing 10 points of high resolution temperature data in a single fiber. The OFT probe is an efficient alternative to thick bundles of arrayed single point temperature probes and expensive MRI thermometry to provide distributed temperature monitoring in tissue. In addition to BPH treatments, all intracavital treatments will benefit from the OFTs in-situ temperature profiling. Due to its nonconducting nature, the optical fiber probe is especially suited to radio frequency and microwave hyperthermia applications. In Phase I, the OFT probe demonstrated temperature measurement every 0.5 cm along the optical fiber with an accuracy of 0.2 degrees C, while reading all 7 points simultaneously in less than 5 seconds. These

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features of our OFT probe have already received keen interest from potential commercial partners. lOS proposes to develop a complete, clinically validated sensor probe with optoelectronic instrumentation as the Phase II end product. PROPOSED COMMERCIAL APPLICATION: As microwave hyperthermia becomes increasingly popular for treatment of benign tumors such as benign prostatic hyperplasia and other benign or malignant tumors, IOS's optical fiber temperature probe will be an integral part of the instrumentation required for effective treatment, providing multipoint, selfcalibrating temperature sensing with high accuracy. Other non-invasive, multipoint thermometric medical applications that are accessible via narrow pathways will benefit from development of this device. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FORMS OF PROSTATE SPECIFIC ANTIGEN AND HK2 IN CANCER Principal Investigator & Institution: Heeb, Mary J.; Scripps Research Institute Tpc7 La Jolla, Ca 92037 Timing: Fiscal Year 2002; Project Start 01-MAY-1993; Project End 31-JAN-2004 Summary: We seek to extend promising studies showing that prostate specific antigen (PSA) and glandular kallikrein (hK2) occur in several forms in blood of prostate cancer (CaP) patients and that measurement of the proportion of PSA in the form of PSAalpha2-macroglobulin (alpha2M) improves the discrimination between early CaP and benign prostatic hyperplasia (BPH). This will be confirmed with well-characterized prospective patient samples. Moreover, we will measure the proportion of PSA in its various forms in these patients, and identify and measure forms of the related novel CaP marker, hK2. We found that hK2 exists in several forms in CaP plasmas, including hK2alpha2M. Clinical assays do not detect PSA-alpha2M and there are no clinical assays for hK2. We will determine which combination of measurements provides the greatest discrimination between CaP and BPH. Since forms of PSA also vary in early vs. advanced CaP, our assays may also be useful in prognosis. The goal is to provide simple ELISA assays that will reduce the invasive, expensive procedures that are needed for diagnosis and ELISAs that are prognostic, to help physicians choose how aggressively to treat CaP patients, or to identify BPH patients who will develop CaP later. It is hypothesized that PSA and hK2 are secreted as zymogens, activated when needed, and then inactivated by protease inhibitors. The pathophysiology of cells that synthesize PSA and hK2 vary in CaP vs. BPH and possibly in different courses of CaP. The time between PSA or hK2 secretion and translocation to the blood may differ, and the enzymes and inhibitors to which they are exposed in the prostate differs from that in blood. Thus, a different spectrum of PSA and hK2 forms will be found in CaP compared to BPH, and in different courses of CaP. To meet our goals, we will: 1. Identify forms of hK2 in CaP and BPH plasmas and develop assays for relevant hK2 forms. Purify hK2 and prepare antibodies and standard hK2-inhibitor complexes for relevant hK2 forms. 2. Prospectively collect serial blood samples from 300 CaP patients and document full histories. Collect prospective samples from 300 undiagnosed patients with elevated PSA. 3. Measure PSA-alpha2M PSA-ACT, free PSA and "total" PSA in each sample and calculate the proportions of each PSA form. Similarly measure relevant hK2 forms. 4. Correlate the proportions of various forms of PSA and hK2 to the course of disease in all CaP patients to determine the prognostic value of each measurement. 5. Correlate the proportions of various forms of PSA and hK2 to the subsequent diagnosis of CaP or BPH in the patients who were undiagnosed. Determine the specificity and sensitivity of each measurement to determine its diagnostic value. Techniques will include protein

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Benign Prostatic Hyperplasia

purification, antibody and ELISA development, immunoblotting, enzyme activity assays, and peptide synthesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FT-IR/GC-MS MODELS FOR PREDICTING PROSTATE CANCER Principal Investigator & Institution: Malins, Donald C.; Pacific Northwest Research Institute 720 Broadway Seattle, Wa 98122 Timing: Fiscal Year 2002; Project Start 15-JAN-1999; Project End 31-DEC-2003 Summary: We have shown that Fourier-transform-infrared (FT-IR) spectroscopy, coupled with advanced statistics, is a powerful means for discriminating between the DNA of normal, pre-malignant and cancer tissues, thus making it possible to establish cancer probability relationships. Previously, we showed that comparable cancer probability relationships could be established using mutagenic and other modified base structures evinced by gas chromatography-mass spectrometry (GC-MS). The overall objective of the proposed work is to further explore the capability of these models for understanding the etiology of prostate cancer and predicting its occurrence at early stages of oncogenesis. The specific aims are (I) to validate, in a blinded study, our published cancer probability models of DNA based on FT-IR/statistics technology for distinguishing between prostate cancer (adenocarcinoma), benign prostatic hyperplasia (BPH) and morphologically normal prostate tissue, using an increased number of cases adjusted for age. This would be expected to confirm our published cancer probability models that were based on a relatively small number of samples; (II) to obtain representative samples from the peripheral, central and transition zones of normal and cancerous prostate glands (from which 70 percent, 20 percent and 10 percent of cancers arise) and determine differences in the DNA structures from each zone, using the FTIR/statistics technology; (III) to determine, with GC-MS, radical- induced base modifications in DNA (e.g., 8-hydroxyguanine) using representative samples from (II) and correlate the results with those obtained by FT-IR/statistics technology; (IV) to determine differences between the DNA of primary prostatic adenocarcinoma and primary tumors that have metastasized based on FT-IR/statistics and GC-MS models; and (V) to apply recently developed equipment for reducing the amount of prostate DNA required for FT-IR spectral analysis to substantially less than a 1.0mug and demonstrate that it produces IR spectra that are statistically indistinguishable from spectra presently obtained with much larger sample sizes. At the conclusion of these studies we expect to have significantly increased understanding of the etiology of prostate cancer and established a promising basis for cancer prediction. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GENETIC POLYMORPHISMS BENIGN PROSTATIC HYPERPLASIA Principal Investigator & Institution: Roberts, Rosebud O.; Associate Professor; Mayo Clinic Coll of Medicine, Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2002; Project Start 16-MAR-2002; Project End 31-JAN-2005 Summary: (provided by applicant) Benign prostatic hyperplasia (BPH) is the most frequent cause of lower urinary tract symptoms and office visits to urologists among elderly men. Despite this, little is known about the etiology and risk factors for BPH and the only proven risk factors for BPH to date are increasing age and an intact androgen metabolism. Estrogens have also been observed to act synergistically with androgens in the development of BPH. Recent studies suggest that the pathogenesis of BPH is related to a decrease in the serum androgen: estrogen ratio with increasing age. Serum hormone

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levels, however, have not been consistently associated with BPH risk, possibly because serum levels may not reflect intracellular hormone levels in prostate cells. Since hormone levels within prostate cells may reflect genetic variations, polymorphisms in genes that regulate intracellular androgen and estrogen levels in prostate cells may play an etiologic role in BPH. Several functionally significant polymorphisms have been described for genes that determine androgen and estrogen levels. These polymorphisms may alter the risk of BPH by altering hormone levels or by their effects on androgen and estrogen receptor-mediated events within the prostate. We propose to test the hypothesis that genetic polymorphisms in sex hormone receptors and sex hormone metabolizing enzymes are etiologic risk factors for BPH. In Specific Aim 1 we will test the association between genetic polymorphisms in androgen and estrogen receptor genes and measures of BPH obtained longitudinally in a cohort of men randomly selected from the community. In Specific Aim 2 we will test the association between polymorphisms in genes that encode enzymes involved in androgen and estrogen biosynthesis and activation and measures of BPH in the same cohort. We will evaluate the CYP11A1, CYP17, CYP19, 3Beta hydroxysteroid dehydrogenase, 17BETA hydroxysteroid dehydrogenase types 2,3, 5, and SRD5A2 genes. In SpecificAim 3 we will test the association between polymorphisms in genes that encode enzymes involved in estrogen bioactivation and inactivation and measures of BPH in the same cohort. These genes include CYP1A1, CYP1A2, CYP1B1, catechol 0-methyl transferase, sulfotransferase 1A1, and glutathione S-transferases (M1, P1, and T1). This communitybased cohort study should provide insights that should improve our understanding of the genetic control of hormonal mechanisms in the pathogenesis of BPH. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GROWTH FACTORS IN PROSTATE CANCER Principal Investigator & Institution: Mc Keehan, Wallace L.; Professor & Center Director; None; Texas A&M University Health Science Ctr College Station, Tx 778433578 Timing: Fiscal Year 2002; Project Start 01-NOV-1993; Project End 30-APR-2003 Summary: Prostate cancer is the most commonly diagnosed malignancy in men, and ranks second in mortality rate after lung cancer in the USA. Cancer and benign prostatic hyperplasia (BPH) is an increasing socio-economic burden on the medical care system with increase in life span of males. Prostate cancer is progressive to malignancy, but occurs primarily in two stages. Type I cancers are largely responsive to anti-androgen treatment, but over long periods progress to the type II malignant and untreatable state. Understanding of the progressive transition from type I to type II states is urgently needed to guide diagnosis, prevention and treatment. The hypothesis underlying this continuation project is that the progression from the non-malignant to malignant states is a stepwise disruption of homeostasis mediated by communication between epithelium and stroma of the prostate. The heparin-binding fibroblast growth factor (FGF) family of polypeptides and its receptor (FGF-R) has been firmly implicated in mediation of growth and differentiation within the prostate. The FGF family is an extremely heterogenous three component system-FGF polypeptides, FGF receptor kinase and FGF heparan sulfate proteoglycan. This project will determine the molecular and cellular mechanisms underlying mediation of homeostasis (growth, growth inhibition/death and differentiation) by specific members of the FGF family in prostate and the changes that occur during progression to malignancy. Specifically, the project will determine (1) the specific roles of stromal derived FGF-7 and FGF-10 in instruction of epithelial phenotypes; (2) the time course and sequence of changes in the FGF signaling system during progression of pre-malignant tumor epithelial cells to

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Benign Prostatic Hyperplasia

malignancy; (3) relative roles of the ecto- and intracellular domains of FGFR1 and FGFR2 in the process; (4) role of androgen and its receptor in squamous versus glandular differentiation; (5) structural motifs in FGFR1 and FGFR2 underlying effects on non-malignant and malignant cell phenotypes; (6) impact of changes in specific pericellular heparan sulfates; (7) conditions that regulate alternate splicing of the FGFR2 gene. Lastly, the project will employ mouse genetics to test the physiological consequence of FGFR1 and FGFR2 on prostate tumor progression. These results will open up new avenues for early diagnosis of prostate tumor potential for progression, for prevention of progression and for treatment of malignancies targeted to the FGFR signaling system. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HEPARIN-BINDING EGF-LIKE FACTORS IN PROSTATE GROWTH Principal Investigator & Institution: Freeman, Michael R.; Director; Children's Hospital (Boston) Boston, Ma 021155737 Timing: Fiscal Year 2002; Project Start 01-AUG-1994; Project End 30-NOV-2004 Summary: The human prostate is particularly susceptible to dysfunction arising grow cell growth abnormalities. Prostate adenocarcinoma is now the most commonly diagnosed cancer among American men, accounting for about 40,000 deaths per year at current rates Benign prostatic hyperplasia (BPH), a non-malignant neoplastic disorder of the human prostate that inhibits urine flow through the prostatic urethra, affects over 800,000 men per year in the US. A majority of men over the age of 50 will occasionally or persistently suffer from symptoms attributable to BPH, including urinary retention, urinary tract injection, hematuria, and bladder muscle dysfunction. Although abnormal tissue expansion is evident in both epithelial and stromal compartments in PH, symptoms are thought to arise primarily from expansion of the stromal compartment and from other neuromuscular abnormalities. This is a competing renewal of a proposal to study the role of heparin-binding epidermal growth factor-like growth factor (MBEGF), and related EGF-like factors, in prostate growth. In the first grant period (7/94 through 3/99) we have accumulated significant evidence that HB-EGF is an important growth factor in the adult human prostate, and therefore of potential physiologic relevance to both benign and malignant prostatic disease. Importantly, we found that (1) HB-EGF is synthesized almost exclusively by smooth muscle cells (SMC) of the interstitital stroma and the vascular bed; and (2) that the membrane form of HB-EGF ("mHB-EGF", for "membrane HB-EGF") was most likely the predominant form of the growth factor present in the prostate under steady-state conditions. In the new proposal we will focus on understanding the role of mHB-EGF as a mediator of cell survival and determine whether mHB-EGF or soluble HB-EGF is a physiologic regulator of human prostate smooth muscle cells. The specific aims of the new proposal are: Specific Aim 1: Determine whether unique binding partners of membrane HB-EGF mediate apoptosis and survival signals. We will test the hypothesis that mHB-EGF acts a survival factor independently of the secreted form of the growth factor and that one or more membrane binding partners, including the tetraspan, protein CD9 and the Bcl-2 binding protein, BAG-1, collaborate with mHB-EGF in this survival activity. Specific Aim 2: Determine the mechanism of HB-EGF growth and survival regulation of prostate SMC. In these experiments we will determine whether mHB-EGF or sHB-EGF is the predominant growth/survival regulator in this cell type and identify and determine the role of possible collaborating proteins. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: HIGH INTENSITY ULTRASOUND FOR PROSTATE TREATMENT Principal Investigator & Institution: Sanghvi, Narendra T.; President; Interscience Research, Inc. Indianapolis, in 46226 Timing: Fiscal Year 2002; Project Start 11-AUG-1998; Project End 30-APR-2004 Description (provided by applicant): High-Intensity Focused Ultrasound (HIFU) phased arrays allow flexibility in beam steering, beam shaping, and dynamic focusing. These features enable them to create large and contiguous tissue lesions of predetermined shape with high efficiency, resulting in shorter treatments, increased accuracy, and ease of operation. The goal of this proposal is to replace the current Sonablate HIFU transducers (mechanically scanned, dual-element, HIFU and imaging capability) used in the clinic for the treatment of BPH and localized prostate cancer with a 2-D HIFU phased array. The array will eliminate "probe switching" during treatment, reduce the reliance on mechanical scanning, and increase treatment effectiveness through dynamic focusing and focal zone shaping. During Phase I, phased array configurations were simulated to determine an optimum design for HIFU prostate treatments. A 1-D truncated spherical annular array and electronics were fabricated and characterized. In this Phase II application, we propose to build on these encouraging results by: 1) defining and optimizing a HIFU phased array with 2-D focusing capability, 2) fabricating and characterizing the array, 3) integrating it into a transrectal image-guided HIFU probe to be used with the Sonablate system, and 4) evaluating its performance invitro and in-vivo using a canine prostate model. PROPOSED COMMERCIAL APPLICATION: As our population ages, prostate disease (BPH & cancer) is becoming an ever-more-frequent malady for man. The annual market for treatment of prostate cancer in the U.S. is estimated around $5 billion. Focus Surgery Inc. manufactures the Sonablate(TM) system, which makes use of HIFU technology to treat benign prostatic hyperplasia (BPH). To extend the application of this system to treat localized prostate cancer increased flexibility in focal spot placement and less reliance on mechanical steering is required. The current proposal directly addresses this challenge. Successful completion of this project will open the enormous market of prostate cancer treatment to our Sonablate(TM) device. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: HORMONAL AND ZINC REGULATION OF PROSTATE M ACONITASE Principal Investigator & Institution: Costello, Les C.; Professor; Oral & Craniofacial Biol Scis; University of Maryland Balt Prof School Baltimore, Md 21201 Timing: Fiscal Year 2002; Project Start 01-JUN-1996; Project End 30-NOV-2004 Summary: Prostate cancer (PCa) is the second leading cause of cancer deaths in males. The diagnosis, treatment, and prevention of PCa are important contemporary issues. New approaches are required to address this major health problem. Important fundamental information and understanding of the pathogenesis and progression are seriously lacking; which contributes to the slow progress in addressing these issues. Compelling evidence now implicates the involvement of altered zinc accumulation and citrate-related metabolism in the pathogenesis and progression of PCa. The most consistent hallmark characteristic of PCa is the inability of the malignant cells to accumulate zinc and citrate as contrasted with the extremely high accumulation of zinc and citrate associated with normal prostate and benign prostatic hyperplasia (BPH). The consistency of this metabolic change is revealed by the fact that in situ MRS determination of prostate citrate levels now provides the most accurate and sensitive

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Benign Prostatic Hyperplasia

test for the detection and localization of malignancy. The key reaction in the metabolic transformation of non-malignant citrate-producing prostate epithelial cells to citrateoxidizing malignant cells is mitochondrial (m-) aconitase. The expression and level of maconitase are regulated by hormones (testosterone and prolactin) and by zinc specifically in prostate cells. In this application, the mechanism and specificity of hormonal regulation of the m-aconitase gene in normal and malignant prostate cells will be established. The role of zinc in modulating the activity and equilibrium of maconitase will be investigated. The studies will be performed with normal fresh prostate epithelial cells obtained from rat prostate tissue; and with human malignant prostate cell lines. The long-term objectives are to understand the unique metabolic relationships associated with the alteration of citrate-related metabolism of normal and malignant prostate cells; to establish the role of zinc and hormones in this altered metabolism, and the implications in the pathogenesis and progression of malignancy. This information will provide new approaches to the diagnosis, prevention, and treatment of PCa. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HUMAN ALDO KETO REDUCTASES AND STEROID HORMONE ACTION Principal Investigator & Institution: Penning, Trevor M.; Professor; Pharmacology; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 22-JUN-2001; Project End 31-MAY-2006 Summary: (Scanned from the applicant's description): Human Aldo-Keto Reductases (AKR) of the AKR1C sub-family include 3alpha-, 17beta-, and 20alpha-hydroxysteroid dehydrogenases (HSDs). By acting as ketosteroid reductases or hydroxysteroid oxidases they can either convert potent sex hormones (androgens, estrogens and progestins) into their cognate inactive metabolites or they can form potent hormones by catalyzing the reverse reactions. The synthesis of sex hormones in target tissues is known as their intracrine formation. Our hypothesis is that tissue specific expression of AKR isoforms regulates the occupancy and trans-activation of steroid hormone receptors and provides a pre-receptor regulation of steroid hormone action. In vitro, recombinant AKR1C2 (formerly type 3 3alpha-HSD) and AKR1C3 formerly type 2 3alpha-HSD and type 5 17beta-HSD) function as 3-, 17 and 20-ketosteroid reductases and as 3alpha-, 17beta- and 20alpha-hydroxysteroid oxidases. Both isoforms are expressed in human prostate and AKR1C3 is dominantly expressed in human mammary gland. The role of AKR1C2 and AKR1C3 in androgen, estrogen and progestin metabolism will be studied by transient and stable expression of their cDNA's into CHOP and human embryonic kidney cells, respectively. Forced expression of AKR1C2 and AKR1C3 in androgen receptor (AR; +/ive) prostate cells (LNCaP and PC3) as well as forced expression of AKR1C3 into estrogen receptor (ERalpha; +/-ive) mammary cells (MCF-7 and MDA-MB-435) will elucidate their roles in steroid hormone metabolism and steroid receptor transactivation. AKR 1 C2- and AKR1C3 expression will be measured in normal, benign prostatic hyperplasia and prostatic carcinoma microdissected sections of radical prostatectomy samples using RT-PCR. Co-localization with the AR will be measured by in situ hybridization and immunohistochemistry. Identical techniques will be used to measure AKR 1 C3 expression and its co-localization with the ER and PR in normal and ductal carcinoma regions of breast biopsy samples. These studies will determine whether AKRs co-localize with steroid receptors and whether AKR expression is associated with disease. Selective AKR1C2 and AKR1C3 inhibitors will be developed from two lead compounds, ursodeoxycholate and N-phenylanthranilic acids (e.g. flufenamic acid). These leads will be used to develop transition-state analogs, tight-

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binding inhibitors, and mechanism-based inactivators. These inhibitors may provide tools to dissect function and provide routes to the first Selective Intracrine Modulators that target AKRs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HUMAN PROSTATIC 3A HYDROXYSTEROID DEHYDROGENASE Principal Investigator & Institution: Lin, Hsueh-Kung; Urology; University of Oklahoma Hlth Sciences Ctr Health Sciences Center Oklahoma City, Ok 73126 Timing: Fiscal Year 2002; Project Start 28-SEP-1998; Project End 31-JUL-2005 Summary: (Adapted from the Applicant's Abstract): In androgen target tissues 3ahydroxysteroid dehydrogenases (3a-HSDs) may regulate the occupancy of androgen receptor (AR) by interconverting 5a-dihydrotestosterone (5a-DHT, a potent androgen) with 5a-androstane-3a,17b-diol (3a-diol, a weak androgen). We have obtained type 2 and type 3 3a-HSD cDNAs expressed in human prostate and overexpressed the enzymes in E. coli. Kinetic studies of these recombinant enzymes show that type 3 3aHSD functions as both a 3a-and 17b-HSD to inactivate active androgens, whereas, type 3 3a-HSD interconverts 5a-DHT with 3a- diol. Levels of 3a-HSD mRNA were higher in primary cultures of prostatic epithelial cells than stromal cells; and elevated levels of 3aHSD mRNA were observed in primary cultures of epithelial cells derived from benign prostatic hyperplasia and prostatic carcinoma tissues. Expression of steady state levels of 3a-HSD mRNA is up-regulated by epidermal growth (EGF) in human prostatic cell lines, LNCaP (androgen sensitive) and PC3 (androgen insensitive). The focus of this proposal is to examine the physiological functions of type 2 and type 3 3a-HSD in regulating androgen metabolism and their activities in modulating prostatic cell proliferation will be investigated. This will be accomplished by stably transfecting type 2 and type 3 3a-HSD cDNAs into these cells. Second, levels of endogenous type 2 and type 3 3a-HSD transcripts will be examined in RNA extracted from the cell lines and normal prostate using ribonuclease protection assay (RPA). Third, EGF-regulated type 2 and type 3 3a-HSD mRNA levels will be examined using RPA. Changes in 3a-HSD expression mediated by EGF will be examined in cell lysates by immunotitration of the enzyme activity. Fourth, to understand the constitutive and EGF- regulated type 2 and type 3 3a-HSD expression in prostatic cells, the 5'-flanking regions of the 3a-HSD genes will be sequenced and cis-acting elements responsible for transcription regulation of two isoforms will be identified. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ISCHEMIC DYSFUNCTION

ETIOLOGY

OF

OBSTRUCTIVE

BLADDER

Principal Investigator & Institution: Levin, Robert M.; Director of Research; Basic & Pharmaceutical Scis; Albany College of Pharmacy 106 New Scotland Ave Albany, Ny 12208 Timing: Fiscal Year 2004; Project Start 01-MAR-2004; Project End 29-FEB-2008 Summary: (provided by applicant): The rabbit model of chronic partial outlet obstruction has proven to be an excellent model for the study of the pathophysiology of human obstructed bladder disease secondary to benign prostatic hyperplasia (BPH). In the rabbit model and in obstructed human bladder tissue, we have identified four defining characteristics of the decompensated (dysfunctional) bladder: 1) cholinergic denervation; 2) mitochondrial dysfunction; 3) decreased sarcoplasmic reticulum (SR) Ca2+ATPase (SERCA) content and activity; and 4) progressive connective tissue (CT)

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Benign Prostatic Hyperplasia

synthesis and redistribution. Results of our recent studies revealed that the rabbit urinary bladders response to partial outlet obstruction is non-uniform, areas of transient focal hypoxia appeared in the bladder wall during the organs initial rapid growth response to obstruction, before any decrease in net bladder blood flow (BF) was observed. Furthermore, these hypoxic foci were clearly visible within the smooth muscle (SM) compartment during compensated bladder function in chronically obstructed rabbits. In addition, EM examination of mildly obstructed bladders revealed focal damage to nerve and muscle cellular and subcellular membranes, i.e., damage was localized only to specific cells within the fields evaluated. From these studies, we have developed the following hypothesis: Ischemia / reperfusion (I/R) - induced membrane damage originates in areas of transient focal hypoxia that first occur in specific regions of the bladder wall during the organs initial response to partial outlet obstruction and are present during compensated function. In the muscle compartment these hypoxic foci are the initiation sites for the contractile and biochemical dysfunctions and smooth muscle collagen synthesis that continue during progressive decompensation. Progression from compensated function to end-stage decompensation occurs as a result of a graduated change from a focal to global response to focal hypoxia; the shift from compensated to decompensated function occurs as membrane damage and collagen synthesis originating in hypoxic foci spreads into normoxic tissue. A corollary of this hypothesis states that aging is accompanied by a loss of antioxidant potential in the bladder resulting in increased sensitivity to I/R damage and increased rate of progression of obstructive bladder dysfunction. The following are our specific aims: Specific Aim 1: To show that I / R - induced focal hypoxic damage begins during the initial response to partial outlet obstruction and continues into and during compensated function. Specific Aim 2" To show that the shift from compensation to decompensation occurs when membrane damage originating in the hypoxic foci spreads into normoxic areas of the bladder wall and that progression to end-stage decompensation occurs as a result of a shift from a focal to a global organ response to focal hypoxia. Specific aim 3: To show that aging results in decreased antioxidant potential of the bladder and an increase in the progression of obstructive bladder dysfunction. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MEDICAL THERAPY AND BENIGN PROSTATE HYPERPLASIA Principal Investigator & Institution: See, William A.; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2002 Summary: The goal of the study is to ascertain if medical therapy with finasteride and/or doxazosin delays or prevents the progression of benign prostatic hyperplasia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MEDICAL THERAPY OF PROSTATIC SYMPTONS (MTOPS) Principal Investigator & Institution: Foley, John P.; Henry M. Jackson Fdn for the Adv Mil/Med Rockville, Md 20852 Timing: Fiscal Year 2002; Project Start 27-APR-1995; Project End 31-MAR-2003 Summary: The objective of this two-by-two, prospective, blinded trial is to determine if finasteride and/or doxazosin will delay or alter the development of benign prostatic hyperplasia (BPH) in a population of at- risk men with mild to moderate symptoms of BPH. Progression of BPH will be defined as development of urinary retention, renal insufficiency, urinary tract infections, or incontinence as well as an increase in the AUA

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symptom score of greater than or equal to 4 points. The trial includes a two-year accrual phase followed by four years of follow-up and a one-year study closeout period. From a large population of retired military health care beneficiaries in the San Antonio metropolitan area, including a large proportion of African American and Hispanic men, the Urology Service, BAMC proposes to identify eligible men for the trial, conduct regular screening clinics and randomize 200 men during a two year period. Particular emphasis will be placed on recruitment of minority populations. Compliance to the dosing schedule of study drugs will be assured through a schedule of regular telephone contacts with participants and will be monitored through regular pill counts. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MINIMALLY INVASIVE SURGERY FOR BPH Principal Investigator & Institution: Lieber, Michael M.; Mayo Clinic Coll of Medicine, Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2002; Project Start 30-SEP-2001; Project End 30-JUN-2006 Summary: (provided by applicant): The objective of this application is for the Department of Urology, Mayo Clinic, Rochester, Minnesota, to become one of the Prostate Evaluation and Treatment Centers (PETC?s) as part of the Minimally Invasive Surgical Therapies (MIST) Treatment Consortium for BPH described in RFA DK-01-024. The purpose of the MIST consortium is to carry out collaborative studies of minimally invasive surgical treatments for lower urinary tract symptoms (LUTS) and benign prostatic hyperplasia (BPH) over the next five years. Minimally invasive surgical therapies for BPH recently have been recognized as an efficient and cost-effective alternative to standard transurethral resection of the prostate (TURP) and open prostatectomy for certain patients with typical symptoms of prostatism. Most urologists now recognize that minimally invasive surgical therapies occupy a useful niche between pharmacologic therapy and surgical procedures which require inpatient hospitalization. However, as stated in the RFA, published reports about minimally invasive therapies are highly variable in entry criteria and have short periods of follow-up, inadequate documentation of follow-up and adverse events, and absence of information on postsurgical pharmacologic therapy. Most studies have been funded by the device makers and are probably not as objective as studies carried out by an independent group such as the MIST consortium. Because of documented interest in carrying out minimally invasive surgical therapies for BPH at this institution as well as past experience of being a useful member of collaborative consortia studying prostate diseases, we believe we can make a useful contribution to the study of Minimally Invasive Surgical Therapies for BPH as a PETC. As an example of the type of MIST research which could be performed in this initiative, we propose a prospective multicenter randomized Phase III comparison of high power KTP laser vaporization prostatectomy (LVP) versus transurethral microwave thermotherapy (TUMT) using the Urologix Targis T3 device. One hundred seventy patients would be randomized to each treatment arm. Follow-up period would be 2 years post-treatment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MINIMALLY INVASIVE SURGICAL THERAPIES CONSORTIUM FOR BP* Principal Investigator & Institution: Hirst, Kathryn; Associate Research Professor; Statistics; George Washington University 2121 I St Nw Washington, Dc 20052 Timing: Fiscal Year 2002; Project Start 30-SEP-2001; Project End 30-JUN-2006

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Benign Prostatic Hyperplasia

Summary: (provided by applicant): The George Washington University Biostatistics Center proposes to work in cooperative agreement with the National Institutes of Diabetes and Digestive and Kidney Diseases (NIDDK) to serve as the Biostatistical Coordinating Center (BCC) for the Minimally Invasive Surgical Therapies (MIST) Consortium for Benign Prostatic Hyperplasia (BPH). The prostate surgeries labeled minimally invasive offer exciting treatment alternatives to the gold standard, transurethral resection of the prostate (TURP). The proposed consortium?s objective is to design and conduct up to four randomized, controlled, multi-center clinical trials to determine the long-term efficacy and safety of minimally invasive therapies for symptomatic benign prostatic hyperplasia (BPH). Researchers and investigators from 15 prostate evaluation and treatment centers (PETC), the NIDDK Division of Kidney, Urologic, and Hematologic Diseases, and the BCC will comprise the consortium and collaborate under a cooperative agreement mechanism. The Steering and Planning Committee, composed of the principal investigators from the BCC and each PETC and the NIDDK project officer, will design and develop each of the clinical trials. The BCC will provide centralized support and biostatistical consultation in: the development of protocols, manuals of procedures, data collection forms, and randomization procedures; implementation of a data management system including data quality assessment; interim analysis of protocol performance, patient safety, and treatment efficacy; and final analysis for publication of results in collaboration with the clinical investigators. The BCC will establish a secure encrypted and password protected web site for study staff to enhance development, distribution, and use of study documents. The application includes a proposed protocol for a 3-arm, placebo/sham controlled, randomized, double-blind clinical trial to address whether the apoptotic effect of neoadjuvant and adjuvant finasteride in combination with the thermal effect of high-energy transurethral microwave thermotherapy (TUMT) act synergistically to destroy more BPH mass and improve outcome than either finasteride alone or TUMT alone. Success is defined as at least 30 percent improvement in AUA symptom score. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MINIMALLY INVASIVE SURGICAL THERAPIES FOR BPH TREATME* Principal Investigator & Institution: Donnell, Robert F.; Director; Surgery; Medical College of Wisconsin Po Box26509 Milwaukee, Wi 532260509 Timing: Fiscal Year 2002; Project Start 30-SEP-2001; Project End 30-JUN-2006 Summary: (provided by applicant): The specific aims of this proposal are to establish the Division of Urology, the Medical College of Wisconsin as a clinical center of excellence for the multi-institutional NIDDK trial entitled "Minimally Invasive Surgical Therapies Treatment Consortium for Benign Prostatic Hyperplasia." The planning for this clinical trial center has been performed to ensure the center?s success in meeting the long-term objectives of the multi-center trial. Specifically, this proposal provides detailed information to establish our ability to meet recruitment goals including minority populations. The following sections outline fail-safe mechanisms in this center design to ensure patient eligibility, data accuracy and efficient data reporting. Two additional considerations central to the design of this clinical center have been the need to maintain patient compliance throughout the duration of enrollment and follow-up, and the need to communicate effectively with the Biostatistical Coordinating Center for this multiinstitutional trial. These tasks will be performed in a timely, efficient, accurate and professional manner to ensure the validity of the data contributed to the trial. This, together with similar contributions from the other clinical trial centers, should allow the

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test hypothesis to be answered, specifically to evaluate the safety and long-term efficacy of minimally invasive therapies for lower urinary tract symptoms. Our study center will participate as members of a group of investigators who will conduct multiple randomized clinical trials, either sequentially or concurrently, of minimally invasive devices for the treatment of symptomatic BPH. The investigators from this study center will develop clinical trials and carry out these trails in accordance with centrally approved protocols. The study center at the Medical College of Wisconsin will enroll 180 patients in this clinical trial. The recruitment and marketing strategies outlined in the following sections will ensure this level of participation as well as maximize the center?s ability to recruit minority populations. The center has been designed to provide all the clinical, laboratory and follow-up data required in the protocol. In summary, this proposal outlines what we believe to be the outstanding credentials of the Division of Urology, the Medical College of Wisconsin to serve as a clinical center in this multiinstitutional trial. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MINIMALLY INVASIVE SURGICAL THERAPIES TREATMENT CONSORT* Principal Investigator & Institution: Roehrborn, Claus G.; Professor and Chair; Urology; University of Texas Sw Med Ctr/Dallas Dallas, Tx 753909105 Timing: Fiscal Year 2002; Project Start 30-SEP-2001; Project End 30-JUN-2006 Summary: (provided by applicant): Lower urinary tract symptoms (LUTS) caused by benign prostatic hyperplasia (BPH) are very common findings in aging men and present a considerable health care burden both in terms of morbidity as well as health care resource utilization. Aside from the standard therapy transurethral resection of the prostate (TURP), medical therapies and minimally invasive surgical therapies (MIST) have been developed over the past decade, which are utilized to varying degreed. Fundamentally, information regarding the relative efficacy and safety, as well as tolerability of these procedures in an outpatient setting under local anesthesia, and importantly, durability of the initial results over intermediate follow-up periods is lacking. Further, due to a lack of understanding of the mechanism of action of some of the treatments, there are no known baseline parameters that could be used as predictors of a successful outcome. The MIST Study Group will develop several clinical trial protocols to address these issues over a 5 year time period. A four-arm randomized trial comparing the safety and efficacy of TURP vs TUMT vs TUNA vs ILTT with a 3 year follow-up is proposed enrolling 600 patients with moderate to severe LUTS and BPH at 15 centers as the first study done by the MIST Study Group with the following objectives: (1). Determine the efficacy of three different minimally invasive surgical therapies (MIST: TUMT, TUNA, Interstitial Laser Thermal Therapy) for LUTS and clinical BPH compared with the standard treatment TURP by electrocautery as measured by a standardized symptom severity assessment instrument (2). Determine the safety and tolerability of three different minimally invasive therapies (TUMT, TUNA, Interstitial Laser Thermal Therapy) for LUTS and clinical BPH compared with the standard treatment TURP by electrocautery (3). Determine the rate of retreatment or secondary treatments following the MIST intervention compared with the standard treatment TURP by electrocautery. (4) Determine whether pre-treatment urodynamic status impacts upon the treatment outcome as defined by symptomatic improvement. (5) Determine the relative efficacy as measured by maximum urinary flow rate, postvoid residual urine volume, prostate volume changes, and serum PSA changes. During the course of this first trial, the MIST Study Group will meet regularly to develop a 2nd,

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3rd and subsequent trials. The nature of these additional trials will depend on a needs assessment, the development of new MIST interventions, the findings obtained in the first trial and other factors. The MIST Study Group will be a blueprint for a technology assessment group applicable to other areas of urology and other medical or surgical subspecialties. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR ANALYSIS OF COLLAGEN IN NON-COMPLIANT BLADDERS Principal Investigator & Institution: Howard, Pamela S.; Associate Professor; Anatomy and Cell Biology; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 30-SEP-1993; Project End 30-NOV-2003 Summary: (Adapted from the Applicant's Abstract): The major goal of this proposal is to determine the cellular and molecular mechanisms responsible for activation of extracellular matrix genes in bladder fibrosis. Congenital and acquired obstructive uropathies, as the sequelae to neurologic lesions (myelomeningocele, tethered cord syndrome) or physical alteration (posterior urethral valves, benign prostatic hyperplasia, radiation therapy) can result in fibrosis of the bladder wall. The applicant has demonstrated that the terminal response is an accumulation of type III collagen in an abnormal location and an alteration in the ratio of types III to I collagen. To evaluate potential molecular control mechanisms responsible for bladder fibrosis, she will utilize a cell culture model system consisting of human bladder wall cells (detrusor smooth muscle cells and lamina propria fibroblasts) and bladder wall cells from mice which carry genetic mutations in the potential regulatory pathway proteins, transforming growth factor-beta (TGFB) and angiotensin. She will test the hypothesis that extracellular matrix changes in bladder wall cells are regulated by expression of transforming grow factor-beta via a cascade mechanism involving a positive feedback response of angiotensin. She will determine the role of these tissue factors in regulating cell growth (hyperplasia), cell enlargement (hypertrophy) and extracellular matrix gene and protein expression. These experiments will allow determination of the molecular and biochemical impact of each stimulus on a given cell type to determine further what role each cell type within the bladder wall contributes to the pathologic process. In vivo model of mice which have been genetically manipulated to produce less type I collagen or type III collagen, thereby producing a bladder model in which the normal type III: type I collagen ratio has been altered. Using length-tension studies and whole bladder cystometry on these genetically altered bladders; biochemical alterations will be correlated to physiologic functional properties (bladder compliance). We will initiate studies in vivo and in vitro to attempt to identify signaling molecules and transcription factors, which are part of the signaling pathways, which lead to bladder fibrosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MOLECULAR ANATOMY OF THE DEVELOPING PROSTATE Principal Investigator & Institution: Wubah, Judith A.; Research Assistant Professor; Biological Sciences; University of Maryland Balt Co Campus Baltimore, Md 21250 Timing: Fiscal Year 2002; Project Start 01-APR-2002 Summary: The prostate gland is the most diseased organ in the human body. A striking feature of prostate biology is that different diseases are typically confined to only one region of the prostate gland such that the peripheral zone accounts for nearly all cases of prostate cancer while benign prostatic hyperplasia is restricted to the transition zone.

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There is a paucity of information on the molecular basis of prostate regionalization and patterning. In an effort to elucidate the cellular and molecular mechanisms that underlie initiation and maintenance of normal prostate growth, with a long-term view towards understanding the basis of human disease susceptibility, we propose a comprehensive study of regional gene expression in developing prostate glands. Using the mouse as a model system, where zones (termed lobes) are readily dissected, I propose to use a genomic approach to identify genes that are locally expressed during prostate growth and differentiation. A preliminary survey employing differential display analysis has covered approximately 20% of all transcribed genes and identified a number of candidate genes that are region-specific. Further characterization of these genes and their roles in prostate development and differentiation may yield insights into the molecular basis of normal prostate development as well as prostate disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HYPERPLASIA

MOLECULAR

DISSECTION

OF

BENIGN

PROSTATIC

Principal Investigator & Institution: Rubin, Mark A.; Associate Professor; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 30-JUN-2005 Summary: (provided by applicant): Benign prostatic hyperplasia (BPH) is an extremely common disease of men over age 50. Seventy percent of men by age 60 and 90% by age 70 have histologic evidence of BPH. BPH is clinically manifested by a cluster of lower urinary tract symptoms. A significant cohort of these older individuals exhibit clinical symptoms of BPH. The precise molecular mediators of BPH have yet to be discovered, however, there is considerable evidence that androgens and race play an important role in this process. Before prognostic markers and rational therapies can be developed to target clinically symptomatic BPH, the molecular alterations associated with it need to be unmasked. Our overall hypothesis is that a distinct set of genes/proteins define BPH, molecularly distinguishing it from prostate cancer and non-hyperplastic benign prostatic epithelia. These "signature" molecules have potential as prognostic markers, therapeutic targets, and may play a role in BPH development or progression. The advent of high throughput genomic and proteomic techniques raises new hopes for identifying novel molecular targets for therapy. In this proposal, we will take a functional genomics approach to molecularly dissect BPH. In Aims 1 and 2, gene and protein expression profiles of BPH will be determined using high-density cDNA microarrays and protein microarrays, respectively. Aims 3 and 4 will validate candidate tissue and serum markers using both local and MTOPS samples. Given this, the specific aims are as follows: Aim 1: Define gene expression profiles of BPH. Aim 2: Define focused proteomic profiles of prostatic tissue from BPH patients. Aim 3: Validation of candidate tissue biomarkers of symptomatic BPH a) Tissue Microarray (TMA) Validation using Michigan samples. b) Validation of tissue markers using MTOPS samples. Aim 4: Validation of candidate serum biomarkers of symptomatic BPH. a) Serum Microarray Validation using Michigan samples. b) Validation of serum markers using MTOPS samples. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MTOPS BIOMARKER UNIT AT THE UNIVERSITY OF PITTSBURGH Principal Investigator & Institution: Getzenberg, Robert H.; Director of Urological Research and Asso; Pathology; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260

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Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 30-JUN-2005 Summary: (provided by applicant): Benign Prostatic Hyperplasia (BPH) is a disease of unknown etiology that significantly affects the quality of life in aging men. Histologic BPH may present itself either as symptomatic or asymptomatic in nature. To elucidate the molecular differences underlying BPH, gene expression profiles from the prostate transition zone tissue have been analyzed using microarrays. A set of 511 differentially expressed genes distinguished symptomatic and asymptomatic BPH. This genetic signature separates BPH from normal tissue but does not appear to change with age. This analysis resulted in the identification of several targets, which appear to differentiate BPH from individuals with symptoms from those with histologic BPH. As a Biomarker Unit of the MTOPS Prostate Sample Analysis Consortium we propose to both utilize these markers in a cooperative nature to analyze the tissue and serum samples collected as part of the Medical Therapy of Prostatic Symptoms clinical trial. Our Biomarker Unit will work closely together with the existing MTOPS Data Coordinating Center, the Pathology Coordinating Center as well as the other awarded Biomarker Units. We hypothesize that the genetic markers that we have identified may correlate with the occurrence of BPH as well as the severity of the BPH, responses to pharmacological agents as well as with clinical parameters obtained as part of the study. This hypothesis will be addressed by conducting the following specific aims: 1) to analyze the expression of JM-27, BMP-5 (list other markers) as well as other markers in biopsy samples obtained from the MTOPS trial as well as normal and BPH (symptomatic and asymptomatic) tissues in our bank and to correlate the abovedescribed markers with both response to therapy and symptom progression; 2) to develop serum-based methodologies for testing the expression of the above-described markers in patient samples obtained from the MTOPS trial as well as from normal and BPH (symptomatic and asymptomatic) individuals from our Institution; and 3) to further develop a system by which other markers developed and prioritized by the MTOPS Consortium can be analyzed. As a component of the MTOPS Consortium, these studies should provide the development of novel biomarkers with utility in diagnosing and characterizing BPH. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NA CHANNELS IN AFFERENTS AFTER BLADDER OBSTRUCTION Principal Investigator & Institution: Steers, William D.; Professor and Chairman; Urology; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-MAY-2007 Summary: (provided by applicant): Benign prostatic hyperplasia (BPH) develops in one out of four men. In excess of $1 billion is spent to relieve bothersome symptoms of BPH due to an overactive bladder (OAB). These symptoms may include urgency, frequency, nocturia and urge incontinence. Symptoms can be relieved by local anesthetics and minimally invasive procedures that blunt sensory input from the bladder and urethra yet fail to un-obstruct. Using the partial urethral ligation model in rodents, investigators postulate that OAB may originate from changes in muscle and nerves in the lower urinary tract. Obstructed (OBS) rats exhibit urinary frequency and detrusor overactivity temporally correlated to the development of afferent hypertrophy, an enhanced spinal reflex, and a rise in nerve growth factor (NGF). Immunity to NGF prevents both neural plasticity and OAB. Therefore, NGF acting as a cytokine is thought to participate in these events, NGF's ability to influence afferent excitability is thought to derive, in part, from altering Na conductances, which in turn depends on Na channel isoform expression. Data suggests that afferents from OBS rats exhibit decreased

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immunohistochemical (IHC) staining for the Nay1.8 isoform. This Na alpha subunit gives rise to tetrodotoxin resistant (TTX-R) sodium (Na) currents in C-fiber afferents. Moreover, an antisense (AS) but not mismatch oligodeoxynucleotide (ODN) against this isoform reduces OAB. We postulate that in OBS rats 1) increased afferent excitability exists, 2) OAB and afferent excitability are due to an alteration in sodium (Na) conductance, 3) knockdown of Na channel isoform(s) using intrathecal AS ODN reduces afferent hyperexcitability and OAB, and 4) NGF participates in the genesis of enhanced afferent excitability, alterations in Na channel function and/or isoform expression. These hypotheses will be tested by determining whether obstruction compared to sham surgery 1) alters electrical properties of labeled afferent bladder neurons based on patch clamp analysis, 2) changes expression of Na channel isoforms using IHC and Western blotting, and 3) whether alterations in excitability or protein expression are reversible with deligation and normalization of voiding behavior. The ability of NGF to orchestrate these events will be elucidated by noting if NGF immunity or trkA antagonists prevent changes in electrical properties and protein expression in OBS compared to controls. Insight into these cellular processes could be exploited to develop afferent based treatments for OAB employing pharmacologic, molecular or gene based strategies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NATURAL HISTORY OF PROSTATISM--THE OLMSTED COUNTY STUDY Principal Investigator & Institution: Jacobsen, Steven J.; Professor and Chair, Epidemiology; Mayo Clinic Coll of Medicine, Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2002; Project Start 30-SEP-2000; Project End 31-AUG-2005 Summary: The Olmsted County Study of Urinary Symptoms and Health Status among Men is a prospective cohort study of urologic aging in a random sample of over 2,000 community-dwelling men. This study has made a number of significant contributions to our understanding of the natural history of signs and symptoms related to benign prostatic hyperplasia (BPH) that are free from the biases present in clinical series of patients. These findings, however, are limited to an initial ten years of follow-up that was funded by Merck Research Labs. Since BPH is a chronic, progressive disease and complications are manifest over extended periods, the continued follow-up of this cohort is necessary to accrue sufficient events to provide long-term risk information. These data are not presently available but are necessary to make informed clinical decisions. Furthermore, extending follow-up will increase the precision of estimates of change in surrogate measures of BPH, providing better insight into what would be expected in community-dwelling men in the absence of a clinical trial setting. The continued follow-up also will provide a better understanding of how serum PSA levels change over time. The specific aims for this application are designed to expand upon our previous findings with an additional four years of follow-up using our wellestablished protocols. We will determine the 14-year progression of clinical (symptoms), physiologic (peak urinary flow rates) and anatomic (prostate volume) surrogate measures of BPH (Aim 1). We will examine how these vary together over time (Aim 2) and gather information on long-term risk of complications and treatment and relate this to the surrogate measures of BPH (Aim 3). We will also assess the longitudinal changes in serum PSA levels (Aim 4) in order to increase our understanding of the relationship between increases in PSA levels and prostate growth in the absence of cancer. Thus, with the completion of these aims, we will have provided much-needed insight into the role of surrogate measures of BPH in understanding the natural history of this condition

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in the community at large. This information will prove useful in the design of future clinical trials and epidemiologic studies. Furthermore, we will have provided information that is necessary for informed clinical decision making for treatment of BPH. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NKX31 AND PROSTATE DEVELOPMENT AND CANCER Principal Investigator & Institution: Abate-Shen, Cory; Professor; Medicine; Univ of Med/Dent Nj-R W Johnson Med Sch Robert Wood Johnson Medical Sch Piscataway, Nj 088545635 Timing: Fiscal Year 2002; Project Start 01-SEP-1998; Project End 30-JUN-2003 Summary: (adapted from investigator's abstract): Inductive signaling interactions between epithelial and mesenchymal cell layers represent one of the principal mechanisms of vertebrate organogenesis. In particular, the prostate arises late in gestation when signals from urogenital sinus mesenchyme induces the urogenital sinus epithelium to form the prostatic buds. Under the influences of androgens, these epithelia buds elongate and undergo ductal morphogenesis, thereby forming the ventral, dorsolateral, and anterior (coagulating gland) lobes of the rodent prostate. The prostate provides an excellent model system for studying inductive epithelialmesenchymal interactions, the role of androgen signaling in the generation of sexual dimorphism, and the molecular mechanisms of ductal morphogenesis. Moreover, the analysis of prostate development is likely to provide insights into human disease, notably benign prostatic hyperplasia (BPH) and prostate carcinoma. The Principal Investigator has identified a novel homeobox gene, termed Nkx3.1 that appears to play an important regulatory role in prostate development. Nkx3.1 is one of the few transcriptional regulators known to be expressed specifically in the prostate during development and adulthood. Importantly, the preliminary analysis of Nkx3.1 null phenotype has demonstrated that Nkx3.1 is required for normal prostate development and function. The regulatory role of Nkx3.1 in prostate development will be investigated by performing a detailed analysis of its biochemical properties, expression pattern, cellular activities, and biological functions as follows: 1) the biochemical properties of the Nkx3.1 protein will be analyzed by examining its requirements for DNA recognition, its transcriptional properties, and its post-translational modification by phosphorylation; 2) the expression pattern and cellular functions of Nkx3.1 will be analyzed by examining the distribution of murine Nkx.3.1 transcripts and protein in the male urogenital system, and investigating the effects of Nkx3.1 on cell proliferation and transformation; and 3) the biological role of Nkx3.1 in development will be analyzed by investigating its role in the male urogenital system, by examining its cell autonomy, and its over-expression in reconstituted prostatic tissue. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PARACRINE INTERACTIONS AND HYPERPLASIA IN THE AGING PRO Principal Investigator & Institution: Macoska, Jill A.; Associate Professor; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2008 Summary: Benign prostatic hyperplasia (BPH) ts one of the most common conditions associated with ageing in men. This direct relationship between the ageing process and BPH incidence and prevalence suggests that certain risk factors associated with BPH

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development increase with the ageing process. We propose that a component of the prostate microenvironment that may 'evolve' during the ageing process and increase the risk for BPH development and progression, namely, the relationship between epithelial and associated fibroblastic cells. To test this possibility, we propose to utilize an in vitro model system developed in our laboratory. The epithelial component of this model comprises N15C6 cells that genotypically and phenotypically resemble primary prostate epithelial cells, and the stromal component consists of fibroblastic cell populations originating from young, middle-aged or elderly cystoprostatectomy patients. Preliminary data utilizing this in vitro model system demonstrates that paracrine interactions with fibroblast cells alter genotypic expression and augment expression of the proliferative phenotype in immortalized epithelial cells. Therefore, this in vitro model system could recapitulate the 'evolution' of paracrine interactions between prostate epithelial cells and associated fibroblastic cells during the ageing process. Based on data acquired from this model, we hypothesize that the composition of proteins secreted by fibroblast cells derived from young, middle-aged and elderly patients may differ in a patient age-dependent manner. If so, we expect that human prostate epithelial cells may respond differentially, both phenotypically and genotypically, to the particular medley of proteins secreted by fibroblast cells derived from young, middleaged and elderly patients, and vice versa. This work will be accomplished through the completion of three specific aims: Specific Aim 1. Elucidate the influence of an ageing tissue microenvironment on prostatic proliferation. Specific Aim 2. Isolate fibroblast- or epithlelial-secreted factors that augment expression of the proliferative phenotype. Specific Aim 3. Elucidate how genotype drives phenotype in the context of an ageing prostate tissue microenvironment. The results of these studies should define the specific epithelial- and fibroblast-secreted proteins and their downstream effectors that augment expression of the proliferative phenotype in the human prostate. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PHYTHOTHERAPY FOR THE TREATMENT OF BPH SYMPTOMS Principal Investigator & Institution: Foster, Harris E.; Associate Professor; Surgery; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-MAR-2009 Summary: (provided by applicant): Benign prostatic hyperplasia (BPH) is the most common non-malignant neoplasm in the aging male. The number of men with lower urinary tract symptoms secondary to BPH, is expected to increase substantially as the population ages. Interest in using complementary and alternative medicines, such as phytotherapy, to prevent and manage health care needs has increased dramatically in recent years. The use of phytotherapy to relieve lower urinary tract symptoms, particularly BPH, has spurred interest in Serenoa repens (Saw palmetto) and Pygeum africanum. Both phytotherapeutic agents are used extensively in this country to relieve symptoms of BPH, but little is known about their mechanism of action, efficacy, safety, or the side effects. Although a number of randomized placebo-controlled trials have been published, all suffer from a variety of shortcomings. A long-term randomized placebo-controlled trial is needed to determine if Serenoa repens or Pygeum africanum prevents clinical progression of BPH. Secondary objectives should include a direct comparison of the two phytotherapeutic agents in their ability to improve the symptoms of BPH, the relationship between prostate size and clinical progression of BPH or regression of symptoms, and the ability of objective diagnostic studies to determine which patients are optimal candidates for phytotherapy. The primary goal of this application is to emphasize the ability of Yale University School of Medicine and Yale

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New Haven Hospital to successfully implement this protocol so that quality data is obtained to achieve the goals of a final protocol yet to be determined. The advantages of this site include: 1) investigators with recent experience in successfully implementing similar including National Institutes of Health (NIH)-sponsored] protocols; 2) an institution with the necessary infrastructure and experience in participating in large multi-center protocols; 3) the presence of the university in an ethnically and socioeconomically diverse community; and 4) peripheral sites in minority communities, that can facilitate inclusion of the historically underserved. The above characteristics and strategies make the Yale University School of Medicine and the Yale-New Haven Hospital an outstanding candidate for a Clinical Center. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PILOT--SCAN FAMILY MEMBERS IN THE GENITOURINARY TRACT Principal Investigator & Institution: Collins, Tucker O.; Professor; Chldrn's Hospital Corporation Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2008 Summary: Growth factor signaling systems play a central role in cellular physiology and have been implicated in a wide range of pathophysiologic responses. In the urogenital system, these conditions include benign prostatic hyperplasia and bladder hypertrophy resulting from obstructive uropathies. Because growth factors can elicit such profound changes in cellular responses, understanding the regulation of expression of these mediators should provide important insights into these adaptations. Transcriptional control mechanisms are thought to play a role in altering the levels of the growth factors expressed by the cells of the urogenital system. One class of transcription factors implicated in both the positive and negative regulation of growth factor genes is the C2H2 type of zinc finger factor. With more than 700 C2H2 zinc finger proteins in the human genome, this is a largely unexplored group of regulators. Some of the C2H2 zinc fingers are associated with conserved functional motifs, such as the SCAN domain. The SCAN domain is a highly conserved 84-residue dimerization motif that is found at the N-terminus of about 10% of C2H2 zinc finger proteins. An attractive possibility is that the domain generates combinatorial diversity within the SCAN family of proteins. Despite the large number of members in this family, remarkably little is known about the domain itself or the functions of most of the proteins defined by the domain. However, some members of the family have been implicated in the regulation of growth and survival factors and preliminary studies suggest that SCAN family members are expressed by some of the cells of the urogenital system. The central hypothesis of this developmental project is that members of the SCAN-ZFP transcription factor family play a key role in the regulation of genes important in tissue renewal in the genitourinary tract. To further investigate this hypothesis, we propose two specific aims to define the relevant SCAN family members and the genes they regulate: Specific Aim 1: Characterize the spatial and temporal expression pattern of selected SCAN-ZFP in the urogenital system; Specific Aim 2: Identify candidate target genes in the genitourinary tract that are transcriptionally regulated by SCAN-ZFP. Collectively, these studies should provide new information about the SCAN family and its target genes in the urogenital system. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PROSTATE GENE EXPRESSION CHANGES ASSOCIATED WITH BPH Principal Investigator & Institution: Slawin, Kevin M.; Associate Professor; Urology; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 30-JUN-2005 Summary: (provided by applicant): Through this application, Baylor College of Medicine responds to RFA: DK-02-017, MTOPS Prostate Samples Analysis Consortium (MPSA). The Baylor Prostate Center proposes to serve as a Biomarker Unit within the MPSA consortium, which will work cooperatively with the other Biomarker Units, the Pathology Coordinating Center, and the NIDDK Project Coordinator to perform basic and translational research on biomarkers for BPH. The PI, Kevin M. Slaw/n, M.D., Director of the Baylor Prostate Center, recruited and managed 200 patients on the MTOPS trial over its seven-year duration. The co-investigators encompass broad interests and expertise in both clinical and basic research in benign prostatic hyperplasia (BPH), molecular epidemiology, biomarkers research, genetic and tissue microarray technology, cell signaling, and sophisticated data mining and statistical analysis of complex biologic data. Drawing from his extensive BPH clinical trials experience and with the resource management skills gained as co-Director of both the Biopsy and the Basic Tissue Research Committees of the MTOPS trial, as the Serum Bank director and member of the Resource Allocation Committee of the Baylor SPORE in Prostate Cancer, and as director of Baylor's Prostate Cancer Screening Program for the past eight years, the PI has the requisite administrative, clinical and basic research experience in BPH and biomarker development and validation to lead this center. Furthermore, the considerable tissue resources available through BPH-sub-studies of the Baylor SPORE in Prostate Cancer, and the expertise in tissue harvesting, cataloguing and banking, and in tissue microarray development and production will serve as a valuable resource for biomarker validation prior to testing on the invaluable and limited MTOPS tissue for the Baylor Center, as well as, for the other MPSA consortium members. Our large prostate cancer screening serum bank, containing frozen sera obtained through a yearly program, contains serial frozen serum samples and clinical data including IPSS, DRE estimated prostate volume, and medical and surgical treatment history for BPH on over 10,000 patients spanning a decade of follow-up. Serum markers that correlate with the presence and severity of BPH or that predict progression or response to medical therapy, identified either by the Baylor Biomarkers Center, or by other Centers could be validated in a Phase II study with these resources, allowing only the best markers for progression to evaluation in Phase III studies using the exhaustible MTOPS serum and tissue bank resources. Through the efforts of this RFA proposal, the Baylor MPSA Center, along with the other centers, the Biostatistics Center and the NIDDK, hopes to answer identify and validate much needed new biomarkers for the detection of BPH and the assessment of risk for disease progression, as well as to gain insight into the molecular correlates that determine response to medical therapies, primarily a-blockers and 5a-reductase inhibitors for this disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PROTEIN MICROARRAYS FOR THE HUMORAL RESPONSE IN CANCER Principal Investigator & Institution: Lubman, David M.; Professor; Chemistry; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2004; Project Start 15-JUN-2004; Project End 31-MAY-2009

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Summary: (provided by applicant): In the proposed research, we plan to develop methods that examine the humoral response to prostate tumor antigens as a diagnostic and prognostic serum biomarker of disease. The method involves the use of protein microarrays produced by the two-dimensional liquid phase fractionation of cell lysates. A pl-based chromatographic separation is utilized in the first dimension to fractionate large numbers of proteins into discrete pH fractions over an extended pH range. In the second dimension, nonporous (NPS) reversed phase (RP) HPLC of each pH fraction will be used to separate out purified proteins to be spotted from the column eluent onto nitrocellulose slides. The result will be a protein microarray consisting of >2500 protein spots that can be tested against patient sera to examine resulting humoral response. The prostate cancer protein microarrays will be used to interrogate serum from healthy control individuals, patients with benign prostatic hyperplasia (BPH), and those with biopsy-proven prostate cancer. Using this approach, we hope to characterize a signature humoral response for patients with prostate cancer. The method arrays proteins from actual tumor cells so that antibodies in patient plasma may react to modified forms of a protein not necessarily produced by other methods. Proteins eliciting a humoral response to serum can be analyzed directly from liquid fractions by mass spectrometry where an accurate MW value and analysis of enzymatic peptide maps by CE-TOF-MS and MALDI-TOF-MS can be used for identification and determination of present modifications. Modified proteins may provide selective response to antibodies in sera that unmodified proteins may not provide. The presence of proteins in the liquid phase makes this method amenable to automated screening of large numbers of samples. The antibody response will be explored for its utility in screening/diagnosis (i.e. to supplement PSA testing) and prognosis (i.e., distinguish between indolent and aggressive prostate cancer). In addition, bioinformatic methods will be used to determine whether subclasses of prostate cancer exist that better discriminate among clinical outcomes. A predictive model will be developed cataloguing clinically meaningful markers based on humoral expression profiles from localized prostate cancer samples; thus, candidate tumor antigens can be identified for further experimental study. Candidate tumor antigens will be further validated using tissue microarrays. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PROTEOMICS HYPERPLASIA.

APPROACHES

TO

BENIGN

PROSTATIC

Principal Investigator & Institution: Liu, Brian C.; Assistant Professor; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 30-JUN-2005 Summary: (provided by applicant): This application is in response to RFA-DK-02-017: MPSA Consortium. The major goal of this application is to assemble a cross-disciplinary group of investigators to identify potential biomarkers that can distinguish benign prostatic hyperplasia (BPH) from prostate cancer and normal prostate. The second goal of this application is to validate these potential biomarkers in a larger context, including the use of well-characterized samples from the Medical Therapy of Prostatic Symptoms (MTOPS) clinical trial. Specifically, we will: 1. Identify disease specific biomarkers in microdissected prostate tissues by surface enhanced laser desorption/ionization timeof-flight (SELDI-TOF) mass spectrometry; 2. Identify and characterize isoforms of prostate specific antigen (PSA) and the various members of the human kallikrein family by immunosorption and tandem mass spectrometry (ms/ms)-based sequence identification; 3. Identify secreted proteins in serum of patients with benign prostatic

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hyperplasia and prostate cancer by SELDI-TOF approaches, and to mine these proteomics data to create predictive models that can stratify samples according to clinical information by using a biomarker patterns recognition software and longitudinal screening algorithms; 4. Identify potential chromosomal locations of underand over-expressed genes between BPH, prostate cancer, and normal prostate by using a simple rapid overview of expression patterns on metaphase chromosomes; and 5. Collaborate with other investigators in the MPSA Consortium by developing a BWH Prostate Bio-Specimen and Informatics Repository consisting of: 1) the acquisition and maintenance of BWH specimens, both serum and limited tissues; 2) the maintenance and update of a virtual clinical information and outcome database; and 3) the storage of remaining RNA, cDNA, and/or protein extracts from dissected specimens. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REGULATION OF HUMAN PROSTATE EPITHELIAL CELL GROWTH Principal Investigator & Institution: Ware, Joy L.; Professor; Pathology; Virginia Commonwealth University Richmond, Va 232980568 Timing: Fiscal Year 2002; Project Start 18-MAY-1998; Project End 28-FEB-2006 Summary: (provided by applicant): Two diseases of the prostatic epithelium, benign prostatic hyperplasia (BPH) and prostate cancer, are among the major health problems faced by American men. Deregulation of prostatic epithelial cell proliferation is a central event in both benign and malignant prostatic disease about The objective of this application is to determine the mechanism(s) by which insulin-like growth factor (IGF) and epithelial growth factor (EGF) regulate the growth of human prostate epithelial cells, with emphasis on interactions between the IGF receptor, EGF receptor and the androgen receptor (AR) networks. The hypothesis to be tested is that androgen-induced genes also inducible by IGF or EGF provide an alternate mechanism for control of prostate epithelial cell proliferation and behavor. We will use a novel, well characterized family of SV40TAg immortalized human prostate epithelial cells, both androgen receptor negative (M12AR-) and androgen receptor positive (M12AR+) to achieve these specific aims: (1) To identify key genes induced in common in androgen receptor positive Ml2 cells by both androgen (DHT) and IGF or EGF by applying cDNA microarray analysis; (2) To determine the mechanism(s) by which IGF and EGF regulate prostate cell growth in vitro and in vivo. Candidate genes will be either over expressed or reduced in expression in the appropriate cell line by transfection or introduction of morpholino antisense oligonucleotides or antisense constructs. Proliferation, apoptosis, and differentiation will be assessed in vitro and in vivo by orthotopic injection into athymic nude mice; (3) To determine the expression patterns of the IGF, EGF, and androgen regulated genes identified in Aim 1 among human benign and malignant prostatic tissues. Prostate tissue arrays will be prepared from 400 prostate cancers and screened by immunohistochemistry or in situ hybridization, to confirm expression and assess the frequency of expression of the genes evaluated in our experimental system. These studies will provide comprehensive and unique insights into the mechanisms by which peptide growth factors provide alternate pathways to control prostate epithelial cell proliferation in benign and malignant states. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ROLE OF FIBROBLAST GROWTH FACTORS IN PROSTATE GROWTH Principal Investigator & Institution: Ittmann, Michael M.; Professor; Pathology; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 30-SEP-1997; Project End 31-AUG-2004 Summary: (Adapted from the Applicant's Abstract): Benign prostatic hyperplasia (BPH) is an extremely common disease of older men which leads to morbidity by obstructing urine outflow. There is a considerable body of evidence implicating increased estrogen, in conjunction with androgens, as an underlying factor in the etiology of BPH, but the mechanism by which these hormonal alterations lead to BPH is unclear. The investigators have shown increased expression of FGF7 and FGF2 in BPH that is correlated with epithelial and stromal proliferation, respectively. The role of androgens and estrogens in controlling FGF7 and FGF2 production in the prostate is either controversial or unknown. They have also shown that paracrine factors secreted by prostatic epithelial cells can stimulate production of FGFs by prostatic stromal cells. For FGF7 this paracrine factor is IL- 1alpha. FGF 17, which can increase proliferation of fibroblastic cells, is also expressed by prostatic epithelial cells. Their hypothesis is that increases in estrogen, in combination with androgen, can synergistically stimulate FGF2 and FGF7 production by stromal cells in BPH, which can be further stimulated by local, epithelial derived paracrine factors that both induce FGF production and enhance proliferation of FGF producing stromal cells. They propose two Specific Aims: Specific Aim 1: Control of FGF7 and FGF2 expression by androgens and estrogens: Using primary cultures of human stromal cell they will assess the effect of androgens, estrogens, and paracrine epithelial factors, alone or in combination, on FGF7 and FGF2 production. They will then determine the mechanism by which FGF protein expression is increased in response to the inducing factors. Finally, they will evaluate the effects of androgens and estrogens on FGF production and proliferation using an in vivo model system in which human tissue is implanted in scid/hpg mice. Specific Aim 2: Control of FGF7 and FGF2 expression by paracrine epithelial factors: Their first goal is to correlate expression of IL- Ialpha with expression of FGF7 to test their hypothesis that FGF7 production can be driven by IL- 1alpha. In vivo they will derive a transgenic mouse line that expresses IL- 1alpha at high concentrations in the prostate and determine whether there is induction of FGF7 expression in parallel with hyperplasia of the prostate. The second goal is to identify the epithelial derived paracrine factor(s) which induces FGF2 production by stromal cells. Their final goal is to define the role of FGF 17 as an epithelial derived paracrine inducer of stromal cell proliferation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ROLE OF IGFBP 2 IN PROSTATE--AGE RELATED CHANGES Principal Investigator & Institution: Chakrabarty, Shilla; Anatomy and Neurosciences; University of Texas Medical Br Galveston 301 University Blvd Galveston, Tx 77555 Timing: Fiscal Year 2002; Project Start 01-AUG-2000; Project End 31-JUL-2005 Summary: The prostate gland is known to become hyperproliferative and display a propensity toward carcinoma, with progression in age. As a result, the frequencies of benign prostatic hyperplasia (BPH) and prostate cancer increase dramatically in elderly men. The Insulin-like growth factor (IGF) system is being increasingly recognized as an important regulator of prostatic functions. Insulin like growth factor binding protein-2 (IGFBP-2) may play a significant role in prostatic growth because: (a) it is a major prostatic binding protein; (b) serum IGFBP-2 levels increase with age; and (c) circulatory

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levels of the protein are dramatically higher in prostate cancer patients compared to those with BPH, or in normal subjects. The role of IGFBP-2 in prostatic growth has not been studied to date. Our preliminary studies with prostate cancer cell lines suggest that IGFBP-2 potentiates the growth of prostate cancer cells by up-regulating IGF-I, while IGFBP-2 antibody (Ab) inhibits these effects. No significant growth modulating effects of IGFBP-2 or its antibody were found on normal prostate epithelial cells obtained from a 40 year old single donor. Based on the results of our preliminary studies, and the fact that prostate cancer develops in old age, I hypothesize that IGFBP-2 is involved in the age-dependent transformation of the prostate from normal to metastatic disease. I speculate that elevation of circulatory IGFBP-2 with age induces malignant transformations in the prostate by up- regulating IGF-I, and by modulating IGF cellular actions. To test my hypothesis, the specific aims of the current proposal are to: (1) study age-related and lobe-specific changes in the morphology and expression of IGF system components in the prostate of rodent models of spontaneous hyperplasia and prostatic carcinoma, and relate these to circulatory levels of IGFBP-2; (2) explore if exogenously administered IGFBP-2 or its antibody can modulate the incidence of malignant transformations in the prostate of rodent models of spontaneous hyperplasia and prostatic carcinoma; (3) examine if IGFBP-2 can modulate the tumorigenic potential of normal and malignant prostatic epithelial cells in vivo and in vitro, and (4) investigate the molecular mechanisms by which IGFBP-2 modulates the growth of normal and malignant prostatic epithelial cells. The importance of the proposed studies lies in the fact that besides establishing a knowledge base on age-related changes in the role of IGFBP-2 in the prostate, it will create new grounds for targeting IGFBP-2 in the early diagnosis, progression, management and treatment of prostate cancer, which affects a large population of elderly men. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SAW PALMETTO EXTRACT IN BENIGN PROSTATIC HYPERPLASIA Principal Investigator & Institution: Avins, Andrew L.; Assistant Clinical Professor; Northern California Institute Res & Educ 4150 Clement Street (151-Nc) San Francisco, Ca 941211545 Timing: Fiscal Year 2001; Project Start 23-AUG-1999; Project End 31-AUG-2004 Summary: This proposal describes a double-blind, placebo-controlled randomized clinical trial of the effect of saw palmetto extract on symptoms, objective parameters of disease severity, and quality of life in men with moderate-to-severe benign prostatic hyperplasia. BPH, one of the most common morbid medical conditions in middle-aged and elderly men, is generally treated with alpha-adrenergic blocking agents, finasteride, surgical interventions, or no specific therapy ("watchful waiting"). In the past several years, however, many patients have begun to self-medicate with an extract of the saw palmetto plant (Serenoa repens), a medicinal herb grown in the southeastern United States. Saw palmetto has become the fifth leading medicinal herb consumed in the U.S. and is considered first-line therapy for BPH in several Western European countries. Several small studies suggest that saw palmetto may have clinical benefit, but the methodologic quality of most prior studies has been poor. Very few side effects of the herb have been observed, but few studies have been conducted for more than three months. We propose to conduct a high-quality clinical trial of saw palmetto, with careful attention to the methodologic deficiencies of prior studies. After a single-blind placebo run-in period, 224 patients with mode moderate-to-severe BPH (American Urological Association Symptom Index score greater than or equal to 8) and objective measurement of urinary obstruction, will be randomized to receive either 160mg BID of the herbal

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extract or an identical placebo. Patients will discontinue any other medical therapy for BPH prior to enrollment and all participants will undergo a trans-rectal ultrasound examination at baseline and closeout. Participants in the trial will be seen at 3-month intervals for a total one-year follow-up. Outcome measurements include changes in the AUASI score (the primary outcome measurement), the peak urinary flow rate, the postvoid residual urine volume, the BPH Impact Index, the Olmstead County Study Questionnaire of BPH-specific symptoms and quality of life, and the Short-Form 36 (a generic health status instrument). Numerous laboratory parameters will measured at intervals throughout the trial and symptomatic side effects will be assessed. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SAW PALMETTO USE AND RISK OF PROSTATE CANCER Principal Investigator & Institution: Lee, I-Min; Assistant Professor of Medicine; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2003; Project Start 18-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): Apart from non-melanoma skin cancer, prostate cancer is the most commonly diagnosed cancer among men in the United States today. In spite of its importance, few modifiable predictors of this disease have been established. Well-established risk factors for prostate cancer (e.g., age) are not amenable to modification and, hence, have limited utility as targets of primary prevention strategies. There is a need to identify other risk factors that can be controlled. 5-alpha reductase, the enzyme that converts testosterone to dihydrotestosterone, has been proposed to play a key role in the etiology of prostate cancer; thus, the NCI is currently testing finasteride, a 5-alpha reductase inhibitor, in the prevention of prostate cancer in an ongoing, randomized clinical trial. No information is available on other agents capable of inhibiting 5-alpha reductase and prostate cancer risk in men. Saw palmetto, derived from the berry of the American palm tree, can inhibit 5-alpha reductase activity. Saw palmetto has been shown to be as effective as finasteride in the treatment of urinary symptoms from benign prostatic hyperplasia. No data are available regarding its association with prostate cancer incidence in men; however, in vitro studies show inhibition of growth of prostate cancer cell lines. Therefore, we propose to conduct a retrospective cohort study among 16,700 physicians (mean age 67 years) to test the hypothesis that saw palmetto use reduces the risk of developing prostate cancer. These men currently are being followed as part of two other funded studies, the Physicians' Health Study I and II. Information on the development of prostate cancer is being collected in these two studies, as is a whole host of other information on health habits and medical history. In this application, we propose to retrospectively collect details on the use of saw palmetto (when started and stopped, dose, brand) by adding questions to the scheduled 72-month follow-up questionnaire in these two other studies. During the proposed period of study, we anticipate that 790 cases of prostate cancer will develop. Power calculations show adequate power to detect a 45% reduction in risk of prostate cancer associated with saw palmetto use. At little additional cost, the data from this study will contribute to the knowledge infrastructure regarding whether large scale, informative trials on saw palmetto use and prostate cancer risk should be supported in the future. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SONIC HEDGEHOG INDUCES PROSTATE DEVELOPMENT Principal Investigator & Institution: Bushman, Wade A.; Professor; Surgery; University of Wisconsin Madison 750 University Ave Madison, Wi 53706

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Timing: Fiscal Year 2002; Project Start 07-JUL-1997; Project End 30-JUN-2006 Summary: (provided by applicant): Benign prostatic hyperplasia (BPH) has been postulated to arise from reactivation of embryonic growth pathways. The major goal of our research is to identify the molecular mechanisms that initiate fetal prostate development and to understand how reactivation of these mechanisms in the adult might cause hyperplasia. The prostate is an accessory exocrine sex organ composed of a secretory ductal system enmeshed in a supporting stroma. During fetal development, buds of urogenital sinus (UGS) epithelium grow into the surrounding mesenchyme and form ducts that grow and branch to form a complex ductal system. We have identified two important regulators of ductal development that exert opposing effects on growth. The first is the gene sonic hedgehog (Shh). Shh expression is upregulated by testosterone and localizes to the epithelium of buds that form the main prostatic ducts and to the epithelium of the growing prostatic ducts. The Shh gene product is a secreted signaling peptide that activates target genes in the adjacent UGS mesenchyme. Shh stimulates epithelial proliferation, induces budding in the UGS and promotes ductal branching during postnatal prostate development. The second factor is the gene Bone morphogenetic protein 4 (Bmp4). Bmp4 is expressed in the UGS mesenchyme. Expression surrounds sites of ductal budding and ensheaths the developing prostate ducts. Bmp4 inhibits epithelial proliferation, restricts ductal budding and restrains ductal branching. Our studies reveal that Shh and Bmp4 are expressed in tightly coordinated, complementary patterns of expression that echo their opposing influences on ductal growth. We propose to evaluate the hypothesis that Shh and Bmp4 collaborate to control prostate ductal budding and branching. We expect to show that Shh and Bmp4 act as independent regulators that control ductal growth by exerting opposing effects on epithelial proliferation. We will characterize the effects of Shh and Bmp4 on ductal growth, link their expression to the influence of testosterone and a regulator of ductal budding (Hox-dIS), and characterize the effects of Shh overactivity and Bmp4 insufficiency on ductal budding and branching. We expect to provide new insights into the regulation of prostate growth that will have particular significance in light of our recent observation that Shh and Bmp4 are re-expressed in BPH. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: STEM CELLS AND DISEASE SUSCEPTIBILITY IN THE PROSTATE Principal Investigator & Institution: Masters, John R.; U of L University College London University College London London, Timing: Fiscal Year 2002; Project Start 01-MAR-2001; Project End 31-JAN-2004 Summary: (Adapted from the Applicant's Abstract): The prostate gland is the site of two of the most frequent diseases that afflict elderly men: benign prostatic hyperplasia (BPH) and prostate cancer. The etiology of both diseases is thought to involve changes in prostate stem cells, the cells that are responsible for the growth and maintenance of the prostate gland. BPH and prostate cancer arise in different zones of the prostate. If the differences in stem cell biology between the different zones of the human prostate are elucidated, it may be possible to identify the factors regulating the major differences in susceptibility to prostate disease and design more effective means of controlling BPH and prostate cancer. The specific aims are to identify the epithelial stem cells in each zone of the human prostate and provide the resources for comparative analysis of gene and protein expression in stem cells of these different zones. The project will use normal human prostate tissue to (1) identify, isolate and characterize the epithelial stem cell population from each zone using flow sorting and lineage analysis, (2) to compare the patterns of differentiation between the zones using multiple immunostaining, and (3) to

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grow and store at least 3 large scale primary cultures of epithelial and mesenchymal cells derived from each zone for future analysis using DNA microarrays and proteomics. It is proposed that this project will lead to a greater understanding of why these two important diseases of elderly men develop in different parts of the prostate and provide the resources needed to develop new strategies for the prevention, management and therapy of BPH and prostate cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: STROMAL HYPERPLASIA

GROWTH

FACTORS

IN

BENIGN

PROSTATIC

Principal Investigator & Institution: Rowley, David R.; Associate Professor; Molecular and Cellular Biology; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 30-SEP-1992; Project End 30-JUN-2004 Summary: Studies from the previous two project periods have characterized properties of ps20, a novel protein secreted by prostate smooth muscle. We have reported the cloning of full length cDNA (rat and human) and genomic DNA (mouse and human). The ps20 protein is a new member of the whey acidic protein (WAP) family. This family exhibits growth and differentiation functions. We have made antibody probes to ps20, localized ps20 expression to smooth muscle cells (SMC) in vivo, produced recombinant biologically active ps20, localized ps20 gene to human chromosome 16q24.3, and identified CD9 as a putative membrane interacting/signaling protein. Expression of ps20 was preferential to smooth muscle in vivo, including prostate gland and vascular smooth muscle. Recombinant ps20 induced phenotypic modulation of prostate smooth muscle cells to the migratory, synthetic phenotype in vitro, characteristic of hyperplastic SMC in vascular wall (atherosclerosis) diseases and in culture. In addition, ps20 blocked TGF-beta1 induced phenotypic modulation of SMCs to the contractile phenotype and maintained cells in the synthetic phenotype. Expression of ps20 was specifically regulated by TGF-beta1 in smooth muscle, suggesting an autocrine negative feedback loop. Immunoprecipitation-Western experiments suggests an interaction between ps20 and the CD9 membrane protein in SMCs. These studies suggest ps20 may be a fundamental mediator of smooth muscle phenotype. Benign prostatic hyperplasia (BPH) is a stromal-based disease typified by hyperplastic smooth muscle and ps20positive SMCs. The present proposal will address the hypothesis that ps20 functions as a key autocrine regulator of synthetic SMC phenotype and that ps20 and the synthetic SMC phenotype play roles in the genesis of BPH. To extend our studies and address this hypothesis in detail we propose: l.) To define the ps20-induced smooth muscle phenotype and identify specific ps20-interacting proteins. 2.) To determine whether there is a correlation between expression of synthetic smooth muscle markers, a nodular BPH phenotype, and ps20 expression in human BPH specimens; 3.) To determine the in vivo function of ps20 by targeted gene knockout in mice, and; 4.) To determine the inductive function of ps20 in vivo by targeted overexpression using prostate tissuetissue recombination mouse models. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: STROMAL-EPITHELIAL INTERACTIONS IN DEVELOPMENT OF BPH Principal Investigator & Institution: Olumi, Aria F.; Beth Israel Deaconess Medical Center St 1005 Boston, Ma 02215 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2008

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Summary: (provided by applicant): My long-term goal is to study the biology of stromal-epithelial interactions in benign prostatic hyperplasia (BPH). Since development, growth and tumorigenesis in the prostate is closely regulated by the stromal-epithelial crosstalk, identifying the signal transduction pathways between prostate epithelial cells and the surrounding stromal cells will enable us to better understand the normal and abnormal biology in prostatic diseases. I hypothesize that expression of particular stromal genes is one of the components that regulates the proliferation, cell death and differentiation of prostatic epithelial cells leading to BPH in adulthood. The Jun-family proteins that are early transcription factor molecules have been shown to regulate stromal-epithelial interactions via paracrine modulation. Moreover, the Jun family member proteins have been shown to play an important role in proper development of the genitourinary organs. The balance between the different Jun-family expression in the stroma may be one of the determinants of the ultimate survival or death signals that the stroma may exert on prostatic epithelial cells. This proposal will address whether paracrine signals form stromal cells with genetically modified Jun-family proteins can regulate epithelial proliferation, cell death and differentiation. Stromal expression of Jun-family proteins will be examined in relation to signal transduction pathways known to be important in prostatic stromal-epithelial interactions. These studies can improve our understanding of normal and abnormal stromal-epithelial interactions that may lead to BPH in adulthood. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SYSTEMATIC ASSESS OF GENE EXPRESSION IN MOUSE PROSTATE Principal Investigator & Institution: Chen, Yong Q.; Associate Professor; Cancer Biology; Wake Forest University Health Sciences Winston-Salem, Nc 27157 Timing: Fiscal Year 2002; Project Start 30-SEP-2000; Project End 31-AUG-2003 Summary: Although our understanding of the molecular mechanisms that underlie early development of the vertebrate embryo has advanced dramatically, there has been much less progress in clarifying the processes that orchestrate the formation of the elaborate structures that make up many of the body's organ systems. Elucidating early steps in genitourinary tract development and subsequent steps in determining and differentiating prostate cell lineages is expected to identify genes important in prostate diseases such as benign prostatic hyperplasia and prostate cancer. Cancer of the prostate is the most commonly diagnosed cancer in males in the United States and is the second leading cause of cancer death in men. Many risk factors for human prostate cancer have been proposed, however, its exact etiology is still largely unknown. Since a wide variety of genetic and genomic approaches are possible in the mouse, systematic assess gene expression of the developing mouse prostate will provide an extremely valuable database for research using this species. In turn, genetic studies in mice are likely to further our understanding of the mechanism of human prostate cancer development. We propose to systematically catalog cell-specific patterns of gene expression in mouse prostate. (1) We will quantify genes that are expressed in the stroma, basal and columnar epitheial cells of the mouse ventral, lateral, dorsal and anterior prostate by microSAGE. A total equal to or greater than1,350,000 transcripts will be determined, with which we will have a 96.6% chance to identify genes that are expressed at 1 copy/cell level. (2) We will compare the gene expression profile between the stroma and epithelial cells in different anatomical locations of the mouse prostate (a total of 75 comparisons). We will confirm SAGE results by real-time PCR quantitation. We will post results on our web site so that the data are available to the entire research

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community. (3) We will compare genes that are differentially expressed during the human prostate tumor progression from normal to BPH, PIN, carcinoma and bone metastases to genes that are expressed in mouse prostate to identify mouse homologues/orthologues. Our study will provide the first comprehensive mouse prostate gene database. More importantly, we will provide a list of candidate genes that are likely to be involved in prostate tumor progression. The data should be a rich, valuable resource for devising future genetic targeting, animal modeling and other experiments related to developmental biology in general and prostate cancer in particular. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: THE EFFICACY OF TUMT AND NEOADJUVANT FINASTERIDE FOR BPH Principal Investigator & Institution: Mcvary, Kevin T.; Associate Professor; Urology; Northwestern University Office of Sponsored Research Chicago, Il 60611 Timing: Fiscal Year 2002; Project Start 30-SEP-2001; Project End 30-JUN-2006 Summary: (provided by applicant): Benign prostatic hyperplasia (BPH) is the most common neoplastic condition afflicting men and constitutes a major factor impacting the health of the American male. The objective of the Minimally Invasive Surgical Therapies (MIST) Consortium for BPH is to design and conduct up to several randomized, controlled, multicenter clinical trials to determine the long-term efficacy and safety of minimally invasive therapies for symptomatic BPH including Transurethral Microwave Thermotherapy (TUMT). The potential advantages of TUMT include the relief of LUTS with an in-office procedure using minimal anesthesia and a rapid recovery. TUMT has been enthusiastically applied to patients with BPH, but reports suffer from lack of uniform outcome measurements and little data on post-surgical pharmacological treatment. One of the goals stated in the RFA is to assess whether adjuvant medical therapy improves the long-term outcome of MIST. In this light, we hypothesize that finasteride can augment the necrosis of prostatic tissue undergoing TUMT by virtue of it ability to induce TGF-beta mediated apoptosis. We propose that this known effect of finasteride will increase the "thermal kill" when used in a neoadjuvant setting with TUMT and result in an improved outcome. This is a truly exciting research direction, with considerable potential ramifications for both the patient and the health care delivery system. We propose an initial clinical trial to address whether the apoptotic effect of neoadjuvant and adjuvant finasteride in combination with the thermal effect of TUMT act synergistically to destroy more BPH mass and improve outcome than either finasteride alone or TUMT alone. We are proposing a 3-arm, placebo/sham controlled, randomized clinical trial using changes in symptoms as the primary Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: THE SYMPATHETIC NERVOUS SYSTEM AND PROSTATIC HYPERPLASIA Principal Investigator & Institution: Walden, Paul D.; Associate Professor; Urology; New York University School of Medicine 550 1St Ave New York, Ny 10016 Timing: Fiscal Year 2002; Project Start 01-SEP-1999; Project End 31-AUG-2004 Summary: Our long-term goal is to understand the pathogenesis of benign prostatic hyperplasia (BPH) on a molecular level thus providing the basis for the development of future therapies as well as preventative strategies for this disease. In BPH, the normal regulation of stromal and epithelial cell growth in the adult prostate is perturbed. It has

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become apparent that androgens, while necessary, are not sufficient for full prostate growth or for the development of BPH. The sympathetic division of the autonomic nervous system controls prostate smooth muscle tone through the action of the sympathetic catecholamine neurotransmitter norepinephrine (NE) on G-protein coupled alpha1-adrenoceptors (alpha1-ARs). There is also compelling evidence from rat and human models that the action of NE on alpha1-ARS stimulates cell proliferation in the prostate independently of androgens. Furthermore, sympathetic activity is known to increase with aging in man and human BPH is associated with clear indications of aberrant sympathetic neurotransmission including alterations both in the number of noradrenergic nerves and in the expression of the mRNAs encoding the three alpha1AR subtypes. These findings indicate that the sympathetic nervous system represents an important androgen independent prostatic growth mechanism. It is our hypothesis that increased sympathetic activity is a critical factor in the causation of BPH. We further hypothesize that increased sympathetic activity results in the altered expression pattern of the alpha1-AR subtype mRNAs seen in BPH which in turn results in increased cell proliferation. We will systematically test our hypothesis by dissecting the mechanism involved in the mitogenic activation of prostatic alpha1-ARS by NE. Specifically we will activate or inhibit specific steps in this signaling pathway and examine the consequences on cell proliferation, cell apoptosis and alpha1-AR We will utilize two model systems for this study. The first is an organ culture system of human prostate tissue, a readily manipulable system that retains cell-cell interactions seen in the intact tissue. The second system is the spontaneously hypertensive rat, an animal model that displays elevated sympathetic activity with concomitant prostatic hyperplasia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: THROMBOSPONDIN-1 IN PROSTATE DEVELOPMENT AND NEOPLASIA Principal Investigator & Institution: Crawford, Susan E.; Associate Professor; Pathology; Northwestern University Office of Sponsored Research Chicago, Il 60611 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2005 Summary: (provided by applicant): Thrombospondin-1 (TSP-1) is a homotrimeric secreted glycoprotein that functions in a wide variety of biologic activities including embryonic development, tissue differentiation, neurite outgrowth, and responses to injury and inflammation. TSP-1 is also a potent inhibitor of angiogenesis, the growth of new blood vessels from the existing vasculature. Decreased TSP-1 expression contributes to the angiogenic environment that supports the growth of glioblastoma, fibrosarcomas and bladder cancer. Data is presented that show TSP-1 expression is down-regulated or lost in benign prostatic hyperplasia (BPH) and prostate cancer and identify TSP-1 as a key functional inhibitor of angiogenesis in the prostate. The normal and diseased prostate is exquisitely sensitive to changes in TSP-1 levels as TSP-1 null mice develop prostatic hyperplasia and TSP-1 expression increased after androgen ablation therapy in human prostate cancer specimens. Thus, we hypothesize that TSP- 1 plays a key role in the regulation of normal prostatic growth and that dysregulated TSP1 expression contributes to disease. To study the functions of TSP-1 in normal prostate growth and discern how dysregulated expression contributes to disease states, we plan to 1) characterize the prostate phenotype in the TSP-1 null mice, establishing a time course of disease development, and determine the underlying mechanism of the hyperplasia (i.e. increased proliferation or angiogenesis, decreased apoptosis or a combination of these), and 2) determine if androgen regulation of TSP-1 expression is critical to modulation of prostatic growth, using in vitro methods and the TSP-1 null

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mouse model. Results from these experiments should establish the function of TSP-1 in prostatic growth regulation and determine how TSP-1 may be useful as a prognostic indicator or as a treatment for prostatic diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TRACKING UROGENITAL SINUS CELL PROGENY Principal Investigator & Institution: Sikes, Robert A.; Assistant Professor; Biological Sciences; University of Delaware Newark, De 19716 Timing: Fiscal Year 2002; Project Start 22-JUL-2002; Project End 30-JUN-2005 Summary: (provided by applicant): The cellular otigins of both benign and malignant prostate neoplasia remain elusive. Subtypes of benign prostatic hyperplasia (BPH) have been shown to respond differentially to androgen withdrawal, 5alpha-reductase inhibitors and alpha-adrenergic blockers. Likewise, malignant prostate cancer and its precursor, high-grade prostatic intra-epithelial neoplasia (PIN), have been shown to exhibit variable hormonal responsiveness with an unpredictable length of remission and time to recurrence. Much of the uncertainties reside in the lack of basic understanding of the origins of tumor epithelium, whether from basal/stem cells, neuroendocrine cells, luminal epithelial cells, or epithelial-mesenchymal interconversion. To gain further insight into the origin of prostate epithelium, efforts have been made to establish relevant tissue culture cell lines for comparative and correlative studies. These approaches have been faced with the criticism that passage of cells in vitro often results in genotypic and phenotypic "drift," which can no longer be used with confidence to define the nature of prostate cells from the diseased state. Moreover, normal prostatic epithelial cells, either immortalized with large T antigens or transfected with ras or myc oncoproteins, have dramatic alterations in phenotype and genotype when compared to prostatic epithelial cells that progress without such specific genetic context. Faced with these deficiencies, methods of analyzing directly clinical specimens using microdissection, high-throughput cDNA microarray and comparative genomic hybridization have been used to delineate the molecular profiling of normal and diseased tissues andcells. In the proposed study, we seek to define the molecular basis of the normal and diseased prostate gland, with special emphasis on cell-lineage relationships through profiling of genes that are associated with urogenital sinus (UGS) epithelium, stromal, ventral pad, {dorsal or ventral UGS}. The hypothesis to be tested is: Differential expression of urogenital sinus "core" genes can be found during neonatal, pubertal and adult prostate development. These marker genes should prove useful in defining the origin of prostate cells in a lobe-specific and defined relationship. Sex steroid administration could affect the developmental "fate" of prostate cells normally under rigid temporal and spatial control. The aims to be pursued in this proposal are: Aim 1 Gene expression profiles will be defined in discrete UGS components, Aim 2 Confirmation of cellular location of UGS core genes in developmental stage-specific prostate glands. Aim 3 Determine changes in the pattern of UGS ?core? genes following various epigenetic stress (estradiol+ testosterone tx., lobe-specific responses to castration). The overall objectives of this proposal are to define the origin of the normal prostate cells with specific emphasis on the primordial origin of these cells based on an understanding of fetal UGS architecture and developmental capacity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: TRANSCRIPTOME ANALYSIS IN NORMAL AND NEOPLASTIC PROSTATE Principal Investigator & Institution: Nelson, Peter S.; Associate Professor; Fred Hutchinson Cancer Research Center Box 19024, 1100 Fairview Ave N Seattle, Wa 98109 Timing: Fiscal Year 2002; Project Start 30-SEP-2000; Project End 31-OCT-2003 Summary: (adapted from the application) The prostate gland contributes to a significant portion of the disease burden involving American males due to the high prevalence and increasing incidence of benign prostatic hyperplasia (BPH) and prostate carcinoma in aging men. Prostate cancer now represents the second leading cause of cancer death in American men. The prevalence of BPH numbers in the tens of millions. Nonetheless, little is known about the molecular factors that contribute to the onset or progression of these diseases. A primary impediment for identifying relevant molecular factors has been the paucity of information regarding the mechanisms of normal prostate growth and differentiation. Few regulatory genes are known to be expressed specifically during prostate development or to be required for prostate function. One approach toward the identification of factors involved in prostate development involves the use of mouse models. The mouse has the significant advantage of having an extensive background of accumulated genetic knowledge. In addition, the mouse genetic program can be manipulated in the form of transgenic and gene deletion animals to provide insights for gene function. We hypothesize that the dysregulation of genes directing the normal development of the prostate gland influence the pathogenesis of prostate diseases including BPH and malignancy. The specific aims of this proposal are to: Aim 1. To establish a virtual and physical cDNA clone archive representing developing, mature, and diseased mouse prostate. Aim 2. To identify specific stromal and epithelial factors responsible for the directed development of mouse prostate. Aim 3. To analyze the expression profiles of prostatic tissues derived from Nkx3.1 and p27Kipl knockout mice and determine their genetic interactions. The accomplishment of these aims will provide a genomics-based resource that defines cell type specific gene expression profiles associated with stages of normal development and neoplastic prostate growth. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: TRANSLATIONAL HYPERPLASIA

RESEARCH

IN

BENIGN

PROSTATIC

Principal Investigator & Institution: Mcconnell, John D.; Executive Vice President; University of Texas Sw Med Ctr/Dallas Dallas, Tx 753909105 Timing: Fiscal Year 2002 Summary: (Adapted from the application) The overall objective of the proposed research is to gain insight into the pathogenesis of benign prostatic hyperplasia (BPH) by applying basic research tools developed in UT Southwestern?s O?Brien Center Research program to the carefully characterized BPH biopsy tissue obtained in the NIHfunded BPF clinical trial (MTOPS). Analysis of prostate tissue and clinical data obtained longitudinally during the course of the five year MTOPS trial can be utilized to characterize the role of specific cellular factors or the development and progression of clinical BPH. The clinical trial endpoints of prostate growth (determined by ultrasound) and time to clinical progression (worsening symptoms) can be correlated with changes in prostatic histology and concomitant alterations in prostate gene expression. The following specific aims will be developed: 1) determine the feasibility of assaying specific gene and protein expression in thin sections of prostate biopsy material; 2) determine if localized increases in stromal cell 5alphareductase type 2 expression

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correlate with localized epithelial cell proliferation; 3) determine the relationship between epithelial cell mass, prostate growth rate and response to androgen withdrawal therapy; 4) using DOC2 as a marker of basal cell differentiation in the prostate, determine whether hyperplastic growth is associated with basal cell de-differentiation and proliferation; 5) to determine whether locally increased expression of specific FGFfamily growth factor correlate with increased rates of prostatic growth. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: UNIVERSITY OF MICHIGAN O'BRIEN CENTER FOR UROLOGY RES. Principal Investigator & Institution: Day, Mark L.; Associate Professor; Urology; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2003; Project Start 15-SEP-2003; Project End 31-AUG-2008 Summary: The O'Brien Urology Research Center at the University of Michigan aims to address a broad range of basic, translational, and clinical concerns relevant to urological diseases. The center will build on a critical mass of urology investigators that comprise a well-established urology research program at the University of Michigan. Toward the O'Brien Center objective, five urology research projects have been assembled that reflect a wide range of investigation across various, different urological diseases. This broad spectrum of investigation is proposed to reflect the unique objective of the O'Brien Award mechanism, that being the advancement of urology research in general. The breadth of our proposed work thus spans from pediatric to adult urological diseases, and from basic science to clinical research. In Project 1, Dr. Jill Macoska will use cDNA microarray expertise, and a unique age-specific stromal and epithelial prostate model, to identify gene expression differences consequent to effects of aging on stromal-epithelial interaction. The findings will have implications for the pathophysiology of benign prostatic hyperplasia (BPH). In Project 2, Dr. John Park will use unique knockout models and cDNA microarrays to further characterize obstruction-induced COX-2 function in collecting duct cells, based on preliminary data implicating increased COX-2 expression in obstructive nephropathy. The findings may guide therapy development for obstructive nephropathy. In Project 3, Dr. Martin Sanda will use hybrid transgenic mouse models to characterize the role of FAS-mediated T cell death as a mediator of prostate-specific T cell tolerance. The findings will have implications for possible immune intervention in benign and malignant prostate diseases. In Project 4, Dr. John Wei and Dr. John Delancey will conduct clinical studies to identify intervention-specific, physiological/anatomic and racial determinants of urinary incontinence natural history and outcome. For this purpose they will use the Incontinence Symptom Index (ISI), a biometrically robust, validated, and broadly applicable instrument for measuring incontinence in multiple domains that they developed in preliminary studies. The findings should improve selection and evaluation of effective interventions for urinary incontinence. In Project 5, Dr. Mark Day will build on preliminary data implicating Rb and androgen receptor (AR) interaction in the regulation of prostate growth to characterize how Rb/E2F1 regulates AR trasncription and activity in vitro and in vivo. The findings have relevance to prostate growth and BPH. These 5 projects will be complemented by a Developmental Award Program that will further broaden the scope of this O'Brien Center to include new investigators in areas such as infertility and urological epidemiology, among others. Interaction between Projects will be facilitated by arl Administrative Core that will provide scientific oversight in the form of a multidisciplinary Center Advisory Board as well as biostatistical support in the form of

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biostatisticians with expertise in eDNA array analysis and in standard analyses for preclinical and clinical models. By embracing a broad range of urology investigation that spans from clinical to basic science, from pediatric to adult urology concerns, the University of Michigan O'Brien Center aims at advances centered on the broad yet common theme of urological research, as uniquely defined by the O'Brien Urology Centers funding mechanism. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: URODYNAMIC AND MULTIETHNIC VARIABILITY OF MEN TREATED B* Principal Investigator & Institution: Kaplan, Steven A.; Professor of Urology, Vice Chair; Urology; Columbia University Health Sciences Po Box 49 New York, Ny 10032 Timing: Fiscal Year 2002; Project Start 30-SEP-2001; Project End 30-JUN-2006 Summary: (provided by applicant): Benign prostatic hyperplasia (BPH) is the most common affliction of men over the age of 50. Despite numerous innovations in therapy for BPH including medical and minimally invasive surgical therapies (MIST), transurethral resection of the prostate (TURP) remains the most effective. In part, the shortcomings of MIST have been the lack of uniform baseline study entry criteria, poor elucidation of baseline criteria aid in therapeutic success and paucity of long-term data. Furthermore, there have been no studies that have attempted to stratify response to therapy based on ethnic variability. Recent data suggests that there may be varying distribution of symptoms, objective diagnoses, and functional / morphologic aspects of the prostate among different ethnic groups. Do minimally invasive alternative surgical therapies result in alternating levels of success among different ethnic groups? The Prostate Center at the New York Presbyterian Medical Center evaluates and treats an ethnically diverse group of more than 1,000 men per year with lower urinary tract symptoms secondary to BPH. In addition it has access to and currently employs all FDA approved MIST procedures, including transurethral microwave thermotherapy, TUNA, interstitial laser, water induced thermotherapy, holmium laser prostatectomy and electrovaporization. We propose to examine the role of MISTs designed to treat BPH a multi - ethnic group. The goals of this clinical trial are to determine the urodynamic changes in bladder function and outlet obstruction in patients with BPH treated by MIST. Parameters to be analyzed include peak detrusor pressure during voiding, detrusor pressure during maximal flow, Shafer resistance curves, Abrams - Griffiths contractility index and detrusor contraction duration. These parameters will be assessed to determine prognostic significance and correlated with long term improvement as determined by changes in the American Urologic Association Symptom Score (AUASx), uroflow and post void residual urine. Specifically, this study aims to evaluate in a highly diverse multi - ethnic population: 1. Urodynamic contractility and resistance parameters which change significantly after MIST 2. Baseline urodynamic parameters which may predict improved outcome after MIST 3. The success of various types of MIST in treating BPH in African - American, Hispanic and Caucasian men. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: UROLOGIC RESEARCH CAREER DEVELOPMENT PROGRAM (T32) Principal Investigator & Institution: Lamb, Dolores; Professor; Urology; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 30-SEP-1999; Project End 29-SEP-2004

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Summary: This application seeks support for a post-doctoral training program in urology based in the Scott Department of Urology at Baylor College of Medicine. The SDU has major ongoing clinical activities, as well as basic research with an emphasis in Prostate Biology, Male Reproductive Biology and Pediatric Urology/Developmental Biology. There are 20 training faculty, 8 of whom have primary appointments in Urology. The training faculty includes 7 M.D.s, 12 Ph.D.s, and 1 M.D./Ph.D. Dr. Lamb will serve as Principal Investigator of the T3 proposal, Dr. Morton will be PI of the K12 proposal, and Dr. Lipshultz will serve as the Director of the Fellowship Training Program. The major research areas in the program include: prostate biology, cell biology, steroid hormone receptors, male reproductive biology, genetics, cell cycle control, aging, human benign prostatic hyperplasia, pediatric urology/developmental biology, gene therapy, and cloning genes. The trainees will be Ph.D. candidates, most likely joining the program directly from completion of graduate school. A focus of our program will be the attraction of highly qualified trainees who seek and intensive substantial research training in Prostate biology, Male Reproductive Biology and Pediatric urology/Developmental Biology, with an emphasis on the clinical translation of the basic research. We have developed a strong recruitment plan, emphasizing the career development of women and minorities in the field. Strengths of the training environment include highly respected, experienced faculty, a high national ranking for research funding, a structured mentoring program and required coursework, a cell biology graduate student program with relevant course work and overall depth in cell biology. Our long-term goals are to train these young investigators to compete successfully for peer-reviewed funding and eventually to increase basic research efforts in Urology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: UROLOGICAL RESEARCH TRAINING GRANT Principal Investigator & Institution: Coffey, Donald S.; Professor; Urology; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 01-MAY-1987; Project End 30-APR-2007 Summary: (provided by applicant): Genitourinary diseases cover abnormal development and growth, benign tumors and malignant cancers, abnormalities in kidney function and stone formation, infections, micturition, impotence and reproductive failure, as well as the neurological and endocrine control of the sex systems. This represents colossal medical problems requiring expertise in many areas of research. There is a critical shortage of trained research scientists in the field of urology. This research training program trains highly qualified young physician scientists for academic careers in urological research and develops young basic scientists (Ph.D. or M.D./Ph.D.) to pursue careers in urological research. Trainees function side-by-side in modern urology research laboratories occupied by 5 full-time Ph.D. basic scientists plus 6 M.D./Ph.D. and 10 M.D. clinical research investigators. These laboratories carry out major funded research programs in the physiology of the smooth muscle of the genitourinary tract, biochemical and physiological studies on benign prostatic hyperplasia, endocrine studies on male secondary sex characteristics, cell biology and structure, mechanisms of action of steroid hormones, genetic studies, neurotransmitter and receptor studies of genitoruinary tissues, reproductive physiology; and basic and clinical studies on cancer. Each trainee participates in a research training program that is customized for his/her particular needs and interests and includes courses in molecular biology, biostatistics, endocrinology, pathology and physiology. The six research trainees are comprised of three types: 1.) Postresident physician scientists - completed

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residency training, spending an additional 1-2 years in research, 2.) M.D. Urological Research Fellows will spend 1 or more years in full time research, and 3.) Postdoctoral Research Fellows - Ph.D. or M.D./Ph.D., in full time research, who have already completed graduate training in a basic science discipline, plus 4.) Predoctoral Trainees, Ph.D. graduate program students carrying out thesis research in the urology labs who are not funded by this grant but who form part of the research-training environment. Each of these four components of our urological training program enriches and contributes to the success of each part. A multidisciplinary environment of graduate students, postdoctorals, postresidency, M.D.'s all doing research within the same environment has proven to be synergistic. The ability to understand the biology of the disease and to work on human pathological material with the application of precise molecular and pathological techniques that are now forthcoming provides a rich environment for future research leaders to study the major medical problems within the field of urology. Past successes of these laboratories in bridging clinical and basic research has produced a large number of scientists and physician scientists who are dedicated to solving urological diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ZINC TRANSPORT RELATIONSHIPS IN PROSTATE CANCER CELLS Principal Investigator & Institution: Franklin, Renty B.; Professor; Oral & Craniofacial Biol Scis; University of Maryland Balt Prof School Baltimore, Md 21201 Timing: Fiscal Year 2004; Project Start 01-AUG-1999; Project End 30-APR-2009 Summary: (provided by applicant): It is well established that prostate cancer (PCa), as contrasted with normal prostate or benign prostatic hyperplasia (BPH), is consistently characterized by dramatic decreases in citrate and zinc levels. Strong and compelling evidence exists that implicate a significant role of altered zinc accumulation in the regulation of citrate metabolism of prostate epithelial cells associated with the development and progression of prostate malignancy. Our broad objectives are to establish the mechanism and regulation of zinc accumulation in normal prostate cells; to determine the alterations that accounts for the loss of zinc accumulation associated with the pathogenesis and progression of malignancy; to establish mechanisms to restore zinc accumulation in malignant and pre-malignant prostate cells; to use this information in the development of new approaches to the diagnosis, treatment and perhaps prevention of prostate malignancy. Normal prostate glandular epithelial cells have the major function and capability of accumulating and secreting the highest levels of both citrate and zinc in the body. We recently established the important link between zinc and citrate; i.e., zinc inhibits (mitochondrial) m-aconitase activity and citrate oxidation of citrate-producing prostate epithelial cells. In PCa, prostate cells undergo a transformation from zinc-accumulating, citrate-producing sane cells to citrate oxidizing malignant cells, due to the lost ability to accumulate high zinc levels. This metabolic transformation occurs early in malignancy and is an apparent requirement for progression of the malignancy. Thus, the mechanism involved in the lost ability to accumulate zinc, which permits the alteration in citrate metabolism, is a key relationship in prostate malignancy. The specific aims of the proposal are: 1. To establish the mechanism by which ZIP1 facilitates the transport of zinc from plasma into the cell. 2. To determine the structure of the regulatory region of the ZIP1 gene that confers prolactin and testosterone regulation. 3. To establish that altered expression of ZIP1 alters the tumorigenicity of prostate cells (PC-3 and LNCaP). 4. To determine if

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decreases expression of ZIP1 and decreased zinc accumulation are characteristics of malignant cells in prostate cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

E-Journals: PubMed Central3 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “benign prostatic hyperplasia” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for benign prostatic hyperplasia in the PubMed Central database: •

Models of DNA structure achieve almost perfect discrimination between normal prostate, benign prostatic hyperplasia (BPH), and adenocarcinoma and have a high potential for predicting BPH and prostate cancer. by Malins DC, Polissar NL, Gunselman SJ.; 1997 Jan 7; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=19308

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Randomised controlled trial of an interactive multimedia decision aid on benign prostatic hypertrophy in primary care. by Murray E, Davis H, Tai SS, Coulter A, Gray A, Haines A.; 2001 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=48138

The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine.6 The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign references. It is also free to use. If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals. To generate your own bibliography of studies dealing with benign prostatic hyperplasia, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “benign prostatic hyperplasia” (or synonyms) into the search box, and click “Go.” The following is 3 4

Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.

With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 5 The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print. 6 PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.

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the type of output you can expect from PubMed for benign prostatic hyperplasia (hyperlinks lead to article summaries): •

A comparative study of terazosin and tamsulosin for symptomatic benign prostatic hyperplasia in Japanese patients. Author(s): Okada H, Kamidono S, Yoshioka T, Okuyama A, Ozono S, Hirao Y, Okajima E, Yamamoto K, Kishimoto T, Park Y, Kurita T. Source: Bju International. 2000 April; 85(6): 676-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10759664

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A current review of medical therapy for benign prostatic hyperplasia. Author(s): Brown GA, Sussman DO. Source: J Am Osteopath Assoc. 2004 February; 104(2 Suppl 2): S11-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15038398

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A randomized controlled trial comparing transurethral resection of the prostate, contact laser prostatectomy and electrovaporization in men with benign prostatic hyperplasia: urodynamic effects. Author(s): Van Melick HH, Van Venrooij GE, Eckhardt MD, Boon TA. Source: The Journal of Urology. 2002 September; 168(3): 1058-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12187222

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A randomized trial comparing holmium laser enucleation of the prostate with transurethral resection of the prostate for the treatment of bladder outlet obstruction secondary to benign prostatic hyperplasia in large glands (40 to 200 grams). Author(s): Tan AH, Gilling PJ, Kennett KM, Frampton C, Westenberg AM, Fraundorfer MR. Source: The Journal of Urology. 2003 October; 170(4 Pt 1): 1270-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14501739

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A randomized, double-blind crossover study of tamsulosin and controlled-release doxazosin in patients with benign prostatic hyperplasia. Author(s): Kirby RS. Source: Bju International. 2003 January; 91(1): 41-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12614248

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A rational approach to benign prostatic hyperplasia evaluation: recent advances. Author(s): Bhargava S, Canda AE, Chapple CR. Source: Current Opinion in Urology. 2004 January; 14(1): 1-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15091041

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A review of guidelines on benign prostatic hyperplasia and lower urinary tract symptoms: are all guidelines the same? Author(s): Irani J, Brown CT, van der Meulen J, Emberton M. Source: Bju International. 2003 December; 92(9): 937-42. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14632851

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A systematic review of holmium laser prostatectomy for benign prostatic hyperplasia. Author(s): Tooher R, Sutherland P, Costello A, Gilling P, Rees G, Maddern G. Source: The Journal of Urology. 2004 May; 171(5): 1773-81. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15076275

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A trial study: the effect of low dose human chorionic gonadotropin on the symptoms of benign prostatic hyperplasia. Author(s): Godschalk MF, Unice KA, Bergner D, Katz PG, Mulligan T, McMichael J. Source: The Journal of Urology. 2003 October; 170(4 Pt 1): 1264-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14501738

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Aetiology and pathogenesis of benign prostatic hyperplasia. Author(s): Eaton CL. Source: Current Opinion in Urology. 2003 January; 13(1): 7-10. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12490809

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Alfuzosin hydrochloride for the treatment of benign prostatic hyperplasia. Author(s): Lee M. Source: American Journal of Health-System Pharmacy : Ajhp : Official Journal of the American Society of Health-System Pharmacists. 2003 July 15; 60(14): 1426-39. Review. Erratum In: Am J Health Syst Pharm. 2004 March 1; 61(5): 437. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12892027

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Alfuzosin, an alpha1-adrenoceptor antagonist for the treatment of benign prostatic hyperplasia: once daily versus 3 times daily dosing in healthy subjects. Author(s): Ahtoy P, Chretien P, Dupain T, Rauch C, Rouchouse A, Delfolie A. Source: Int J Clin Pharmacol Ther. 2002 July; 40(7): 289-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12139205

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Alpha1-adrenergic receptors and their inhibitors in lower urinary tract symptoms and benign prostatic hyperplasia. Author(s): Roehrborn CG, Schwinn DA. Source: The Journal of Urology. 2004 March; 171(3): 1029-35. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14767264

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Analysis and reliability of data from 24-hour frequency-volume charts in men with lower urinary tract symptoms due to benign prostatic hyperplasia. Author(s): Gisolf KW, van Venrooij GE, Eckhardt MD, Boon TA. Source: European Urology. 2000 July; 38(1): 45-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10859441

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Androgen receptor gene polymorphisms and increased risk of urologic measures of benign prostatic hyperplasia. Author(s): Roberts RO, Bergstralh EJ, Cunningham JM, Hebbring SJ, Thibodeau SN, Lieber MM, Jacobsen SJ. Source: American Journal of Epidemiology. 2004 February 1; 159(3): 269-76. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14742287

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Apoptotic and proliferative index after Alpha-1-adrenoceptor antagonist and/or finasteride treatment in benign prostatic hyperplasia. Author(s): Erdogru T, Ciftcioglu MA, Emreoglu I, Usta MF, Koksal T, Ozbilim G, Gulkesen KH, Baykara M. Source: Urologia Internationalis. 2002; 69(4): 287-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12444285

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Are neuroendocrine cells responsible for the development of benign prostatic hyperplasia? Author(s): Islam MA, Kato H, Hayama M, Kobayashi S, Igawa Y, Ota H, Nishizawa O. Source: European Urology. 2002 August; 42(2): 79-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12160576

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Are stents still a useful therapy for benign prostatic hyperplasia? Author(s): Ogiste JS, Cooper K, Kaplan SA. Source: Current Opinion in Urology. 2003 January; 13(1): 51-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12490816

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AUA guideline on management of benign prostatic hyperplasia (2003). Chapter 1: Diagnosis and treatment recommendations. Author(s): AUA Practice Guidelines Committee. Source: The Journal of Urology. 2003 August; 170(2 Pt 1): 530-47. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12853821

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Benign prostatic hyperplasia and prostate carcinoma in native Africans. Author(s): Dawam D, Rafindadi AH, Kalayi GD. Source: Bju International. 2000 June; 85(9): 1074-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10848698

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Benign prostatic hyperplasia and sexual dysfunction. Author(s): Quinn MJ. Source: Lancet. 2003 May 3; 361(9368): 1562. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12737897

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Benign prostatic hyperplasia and sexual dysfunction. Author(s): Jefferson K, Persad R. Source: Lancet. 2003 May 3; 361(9368): 1562. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12737896

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Benign prostatic hyperplasia in elderly Thai men in an urban community: the prevalence, natural history and health related behavior. Author(s): Tantiwong A, Nuanyong C, Vanprapar N, Swasdipala P, Chittapraphai S. Source: J Med Assoc Thai. 2002 March; 85(3): 356-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12117026

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Benign prostatic hyperplasia management--statistical significance may not translate into clinical relevance. Author(s): Kaplan SA. Source: The Journal of Urology. 2004 March; 171(3): 1207-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14767302

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Benign prostatic hyperplasia progression and its impact on treatment. Author(s): Djavan B, Waldert M, Ghawidel C, Marberger M. Source: Current Opinion in Urology. 2004 January; 14(1): 45-50. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15091050

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Benign prostatic hyperplasia, prostate cancer and other prostate diseases diagnosed as a result of screening procedure among 1,004 men in the Lublin district. Author(s): Opalinska E, Stoma F, Michalak A, Latalski M, Goniewicz M. Source: Ann Univ Mariae Curie Sklodowska [med]. 2002; 57(1): 493-501. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12898966

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Benign prostatic hyperplasia. Author(s): Doherty AP. Source: Hosp Med. 2003 February; 64(2): 114. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12619342

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Benign prostatic hyperplasia. Author(s): Kring D. Source: Nursing. 2003 May; 33(5): 44-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12792570

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Benign prostatic hyperplasia. Author(s): Thorpe A, Neal D. Source: Lancet. 2003 April 19; 361(9366): 1359-67. Review. Erratum In: Lancet. 2003 August 9; 362(9382): 496. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12711484

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Benign prostatic hyperplasia: a progressive disease of aging men. Author(s): Emberton M, Andriole GL, de la Rosette J, Djavan B, Hoefner K, Vela Navarrete R, Nordling J, Roehrborn C, Schulman C, Teillac P, Tubaro A, Nickel JC. Source: Urology. 2003 February; 61(2): 267-73. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12597928

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Benign prostatic hyperplasia: from A - Z. Author(s): Elhilali MM, Nickel JC. Source: Can J Urol. 2003 April; 10(2): 1799-802. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12773230

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Benign prostatic hyperplasia: medical management considering sexual function and prostate cancer. Author(s): Finkelstein LH. Source: J Am Osteopath Assoc. 2004 February; 104(2 Suppl 2): 1 P Preceding S1. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15038395

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Benign prostatic hyperplasia: the opposite effects of alcohol and coffee intake. Author(s): Gass R. Source: Bju International. 2002 November; 90(7): 649-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12410741

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Benign prostatic hyperplasia-associated prostate-specific antigen (BPSA) shows unique immunoreactivity with anti-PSA monoclonal antibodies. Author(s): Wang TJ, Slawin KM, Rittenhouse HG, Millar LS, Mikolajczyk SD. Source: European Journal of Biochemistry / Febs. 2000 July; 267(13): 4040-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10866804

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Body size and serum levels of insulin and leptin in relation to the risk of benign prostatic hyperplasia. Author(s): Dahle SE, Chokkalingam AP, Gao YT, Deng J, Stanczyk FZ, Hsing AW. Source: The Journal of Urology. 2002 August; 168(2): 599-604. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12131317

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Calculated fast-growing benign prostatic hyperplasia--a risk factor for developing clinical prostate cancer. Author(s): Hammarsten J, Hogstedt B. Source: Scandinavian Journal of Urology and Nephrology. 2002; 36(5): 330-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12487736

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Cellular localization of fibroblast growth factor 2 (FGF-2) in benign prostatic hyperplasia. Author(s): Sinowatz F, Schams D, Einspanier R, Arnold G, Pfeffer M, Temmim-Baker L, Amselgruber W, Plendl J. Source: Histology and Histopathology. 2000 April; 15(2): 475-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10809367

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Cellular senescence in the pathogenesis of benign prostatic hyperplasia. Author(s): Castro P, Giri D, Lamb D, Ittmann M. Source: The Prostate. 2003 April 1; 55(1): 30-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12640658

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Changes in medicare reimbursement: impact on therapy for benign prostatic hyperplasia. Author(s): Donnell RF. Source: Curr Urol Rep. 2002 August; 3(4): 280-4. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12149158

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Changes in nocturia from medical treatment of benign prostatic hyperplasia: secondary analysis of the Department of Veterans Affairs Cooperative Study Trial. Author(s): Johnson TM 2nd, Jones K, Williford WO, Kutner MH, Issa MM, Lepor H. Source: The Journal of Urology. 2003 July; 170(1): 145-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12796667

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Changing aspects in the evaluation and treatment of patients with benign prostatic hyperplasia. Author(s): Lam JS, Cooper KL, Kaplan SA. Source: The Medical Clinics of North America. 2004 March; 88(2): 281-308. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15049579

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Clinical significance of alpha1-adrenoceptor selectivity in the management of benign prostatic hyperplasia. Author(s): Clin Evid. 2002 Dec;(8):849-63 Source: International Urology and Nephrology. 2001; 33(3): 407-12. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12603916

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Common conditions of the aging male: erectile dysfunction, benign prostatic hyperplasia, cardiovascular disease and depression. Author(s): Zakaria L, Anastasiadis AG, Shabsigh R. Source: International Urology and Nephrology. 2001; 33(2): 283-92. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12092641

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Comparison of MR imaging and urodynamic findings in benign prostatic hyperplasia. Author(s): Alam AM, Sugimura K, Okizuka H, Ishida J, Igawa M. Source: Radiat Med. 2000 March-April; 18(2): 123-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10888045

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Comparison of prazosin, terazosin and tamsulosin in the treatment of symptomatic benign prostatic hyperplasia: a short-term open, randomized multicenter study. BPH Medical Therapy Study Group. Benign prostatic hyperplasia. Author(s): Tsujii T. Source: International Journal of Urology : Official Journal of the Japanese Urological Association. 2000 June; 7(6): 199-205. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10843450

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Comparison of tamsulosin and finasteride for lower urinary tract symptoms associated with benign prostatic hyperplasia in Korean patients. Author(s): Lee E. Source: J Int Med Res. 2002 November-December; 30(6): 584-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12526285

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Consensus statement: the role of prostate-specific antigen in managing the patient with benign prostatic hyperplasia. Author(s): Bartsch G, Fitzpatrick JM, Schalken JA, Isaacs J, Nordling J, Roehrborn CG. Source: Bju International. 2004 March; 93 Suppl 1: 27-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15009083

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Cooled thermotherapy for the treatment of benign prostatic hyperplasia: durability of results obtained with the Targis System. Author(s): Miller PD, Kastner C, Ramsey EW, Parsons K. Source: Urology. 2003 June; 61(6): 1160-4; Discussion 1164-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12809888

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Cost-effectiveness of new treatments for benign prostatic hyperplasia: results of a randomized trial comparing the short-term cost-effectiveness of transurethral interstitial laser coagulation of the prostate, transurethral microwave thermotherapy and standard transurethral resection or incision of the prostate. Author(s): Norby B, Nielsen HV, Frimodt-Moller PC. Source: Scandinavian Journal of Urology and Nephrology. 2002; 36(4): 286-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12201922

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Counting the cost of treating benign prostatic hyperplasia. Author(s): Foley CL, Taylor C, Kirby RS. Source: Bju International. 2004 February; 93(3): 250-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14764116

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Current treatment options for benign prostatic hyperplasia and their impact on sexual function. Author(s): Larson TR. Source: Urology. 2003 April; 61(4): 692-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12670545

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CYP17 polymorphisms in relation to risks of prostate cancer and benign prostatic hyperplasia: a population-based study in China. Author(s): Madigan MP, Gao YT, Deng J, Pfeiffer RM, Chang BL, Zheng S, Meyers DA, Stanczyk FZ, Xu J, Hsing AW. Source: International Journal of Cancer. Journal International Du Cancer. 2003 November 1; 107(2): 271-5. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12949806

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Cytokine expression pattern in benign prostatic hyperplasia infiltrating T cells and impact of lymphocytic infiltration on cytokine mRNA profile in prostatic tissue. Author(s): Steiner GE, Stix U, Handisurya A, Willheim M, Haitel A, Reithmayr F, Paikl D, Ecker RC, Hrachowitz K, Kramer G, Lee C, Marberger M. Source: Laboratory Investigation; a Journal of Technical Methods and Pathology. 2003 August; 83(8): 1131-46. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12920242

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Data from frequency-volume charts versus filling cystometric estimated capacities and prevalence of instability in men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia. Author(s): van Venrooij GE, Eckhardt MD, Gisolf KW, Boon TA. Source: Neurourology and Urodynamics. 2002; 21(2): 106-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11857662

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Data from frequency-volume charts versus maximum free flow rate, residual volume, and voiding cystometric estimated urethral obstruction grade and detrusor contractility grade in men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia. Author(s): Van Venrooij GE, Eckhardt MD, Boon TA. Source: Neurourology and Urodynamics. 2002; 21(5): 450-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12232879

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Data from frequency-volume charts versus symptom scores and quality of life score in men with lower urinary tract symptoms due to benign prostatic hyperplasia. Author(s): van Venrooij GE, Eckhardt MD, Gisolf KW, Boon TA. Source: European Urology. 2001 January; 39(1): 42-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11173938

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Day-case local anaesthetic radiofrequency thermal ablation of benign prostatic hyperplasia: a four-year follow-up. Author(s): Syed AH, Stewart LH, Hargreave TB. Source: Scandinavian Journal of Urology and Nephrology. 2000 October; 34(5): 309-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11186469

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Decreased suburethral prostatic microvessel density in finasteride treated prostates: a possible mechanism for reduced bleeding in benign prostatic hyperplasia. Author(s): Hochberg DA, Basillote JB, Armenakas NA, Vasovic L, Shevchuk M, Pareek G, Fracchia JA. Source: The Journal of Urology. 2002 April; 167(4): 1731-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11912398

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Detection of prostate cancer and changes in prostate-specific antigen (PSA) six months after surgery for benign prostatic hyperplasia in patients with elevated PSA. Author(s): Ozden C, Inal G, Adsan O, Yazici S, Ozturk B, Cetinkaya M. Source: Urologia Internationalis. 2003; 71(2): 150-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12890951

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Determination of transition zone volume by transrectal ultrasound in patients with clinically benign prostatic hyperplasia: agreement with enucleated prostate adenoma weight. Author(s): Baltaci S, Yagci C, Aksoy H, Elan AH, Gogus O. Source: The Journal of Urology. 2000 July; 164(1): 72-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10841600

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Development of a new in vitro model for the study of benign prostatic hyperplasia. Author(s): Habib FK, Ross M, Bayne CW. Source: Prostate Suppl. 2000; 9: 15-20. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11056497

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Differential response of prostate specific antigen to testosterone surge after luteinizing hormone-releasing hormone analogue in prostate cancer and benign prostatic hyperplasia. Author(s): Agarwal DK, Costello AJ, Peters J, Sikaris K, Crowe H. Source: Bju International. 2000 April; 85(6): 690-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10759667

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Dihydrotestosterone and the concept of 5alpha-reductase inhibition in human benign prostatic hyperplasia. Author(s): Bartsch G, Rittmaster RS, Klocker H. Source: European Urology. 2000 April; 37(4): 367-80. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10765065

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Dihydrotestosterone and the concept of 5alpha-reductase inhibition in human benign prostatic hyperplasia. Author(s): Bartsch G, Rittmaster RS, Klocker H. Source: World Journal of Urology. 2002 April; 19(6): 413-25. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12022710

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Discontinuation of alpha-blockade after initial treatment with finasteride and doxazosin in men with lower urinary tract symptoms and clinical evidence of benign prostatic hyperplasia. Author(s): Baldwin KC, Ginsberg PC, Roehrborn CG, Harkaway RC. Source: Urology. 2001 August; 58(2): 203-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11489700

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Distribution of inflammation, pre-malignant lesions, incidental carcinoma in histologically confirmed benign prostatic hyperplasia: a retrospective analysis. Author(s): Di Silverio F, Gentile V, De Matteis A, Mariotti G, Giuseppe V, Luigi PA, Sciarra A. Source: European Urology. 2003 February; 43(2): 164-75. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12565775

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Does the prostatic vascular system contribute to the development of benign prostatic hyperplasia? Author(s): Ghafar MA, Puchner PJ, Anastasiadis AG, Cabelin MA, Buttyan R. Source: Curr Urol Rep. 2002 August; 3(4): 292-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12149160

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Doppler resistive index in benign prostatic hyperplasia: correlation with ultrasonic appearance of the prostate and infravesical obstruction. Author(s): Kojima M, Ochiai A, Naya Y, Okihara K, Ukimura O, Miki T. Source: European Urology. 2000 April; 37(4): 436-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10765074

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Doxazosin controlled release vs tamsulosin in the management of benign prostatic hyperplasia: an efficacy analysis. Author(s): Kirby RS, Quinn S, Mallen S, Jensen D. Source: Int J Clin Pract. 2004 January; 58(1): 6-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14994963

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Drug or symptom-induced depression in men treated with alpha 1-blockers for benign prostatic hyperplasia? A nested case-control study. Author(s): Clifford GM, Farmer RD. Source: Pharmacoepidemiology and Drug Safety. 2002 January-February; 11(1): 55-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11998552

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Drug treatment of benign prostatic hyperplasia and hospital admission for BPHrelated surgery. Author(s): Souverein PC, Erkens JA, de la Rosette JJ, Leufkens HG, Herings RM. Source: European Urology. 2003 May; 43(5): 528-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12705998

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Durability of results obtained with transurethral microwave thermotherapy in the treatment of men with symptomatic benign prostatic hyperplasia. Author(s): Ramsey EW, Dahlstrand C. Source: Journal of Endourology / Endourological Society. 2000 October; 14(8): 671-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11083410

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Dutasteride: a new 5-alpha reductase inhibitor for men with lower urinary tract symptoms secondary to benign prostatic hyperplasia. Author(s): Brown CT, Nuttall MC. Source: Int J Clin Pract. 2003 October; 57(8): 705-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14627182

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Early treatment of benign prostatic hyperplasia: implications for reducing the risk of permanent bladder damage. Author(s): Tubaro A, Carter S, Trucchi A, Punzo G, Petta S, Miano L. Source: Drugs & Aging. 2003; 20(3): 185-95. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12578399

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EAU Guidelines on benign prostatic hyperplasia (BPH). Author(s): de la Rosette JJ, Alivizatos G, Madersbacher S, Perachino M, Thomas D, Desgrandchamps F, de Wildt M; European Association of Urology. Source: European Urology. 2001 September; 40(3): 256-63; Discussion 264. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11684840

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Effect of diabetes mellitus on lower urinary tract symptoms and dysfunction in patients with benign prostatic hyperplasia. Author(s): Boon TA, Van Venrooij GE, Eckhardt MD. Source: Curr Urol Rep. 2001 August; 2(4): 297-301. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12084255

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Effect of diabetes on lower urinary tract symptoms in patients with benign prostatic hyperplasia. Author(s): Michel MC, Mehlburger L, Schumacher H, Bressel HU, Goepel M. Source: The Journal of Urology. 2000 June; 163(6): 1725-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10799169

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Effect of doxazosin on stretch-activated adenosine triphosphate release in bladder urothelial cells from patients with benign prostatic hyperplasia. Author(s): Sun Y, MaLossi J, Jacobs SC, Chai TC. Source: Urology. 2002 August; 60(2): 351-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12137852

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Effect of terazosin on clinical benign prostatic hyperplasia in older adults. Author(s): Mudiyala R, Ahmed A. Source: Journal of the American Geriatrics Society. 2003 March; 51(3): 424-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12588590

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Effects of finasteride and cyproterone acetate on hematuria associated with benign prostatic hyperplasia: a prospective, randomized, controlled study. Author(s): Perimenis P, Gyftopoulos K, Markou S, Barbalias G. Source: Urology. 2002 March; 59(3): 373-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11880073

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Effects of finasteride on serum testosterone and body mass index in men with benign prostatic hyperplasia. Author(s): Roehrborn CG, Lee M, Meehan A, Waldstreicher J; PLESS Study Group. Source: Urology. 2003 November; 62(5): 894-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14624915

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Effects of transurethral resection of prostate on the quality of life of patients with benign prostatic hyperplasia. Author(s): O'Sullivan M, Murphy C, Deasy C, Iohom G, Kiely EA, Shorten G. Source: Journal of the American College of Surgeons. 2004 March; 198(3): 394-403. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14992742

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Efficacy and safety of a dual inhibitor of 5-alpha-reductase types 1 and 2 (dutasteride) in men with benign prostatic hyperplasia. Author(s): Roehrborn CG, Boyle P, Nickel JC, Hoefner K, Andriole G; ARIA3001 ARIA3002 and ARIA3003 Study Investigators. Source: Urology. 2002 September; 60(3): 434-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12350480

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Efficacy and safety of intraprostatic temperature-controlled microwave thermotherapy in patients with benign prostatic hyperplasia: results of a prospective, open-label, single-center study with 1-year follow-up. Author(s): Gravas S, Laguna MP, de la Rosette JJ. Source: Journal of Endourology / Endourological Society. 2003 August; 17(6): 425-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12965071

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Efficacy and safety of once-daily alfuzosin in the treatment of lower urinary tract symptoms and clinical benign prostatic hyperplasia: a randomized, placebocontrolled trial. Author(s): Roehrborn CG. Source: Urology. 2001 December; 58(6): 953-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11744466

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Efficacy and tolerability of doxazosin and finasteride, alone or in combination, in treatment of symptomatic benign prostatic hyperplasia: the Prospective European Doxazosin and Combination Therapy (PREDICT) trial. Author(s): Kirby RS, Roehrborn C, Boyle P, Bartsch G, Jardin A, Cary MM, Sweeney M, Grossman EB; Prospective European Doxazosin and Combination Therapy Study Investigators. Source: Urology. 2003 January; 61(1): 119-26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12559281

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Epidemiological survey of benign prostatic hyperplasia and prostatic cancer in China. Author(s): Gu F. Source: Chinese Medical Journal. 2000 April; 113(4): 299-302. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11775222

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Ethanol injection for the treatment of benign prostatic hyperplasia. Author(s): Kim ED. Source: Curr Urol Rep. 2002 August; 3(4): 276-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12149157

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Evaluation of symptoms and quality of life in men with benign prostatic hyperplasia. Author(s): Barry MJ. Source: Urology. 2001 December; 58(6 Suppl 1): 25-32; Discussion 32. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11750246

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Evaluation of the clinical performance of equimolar- and skewed-response total prostate-specific antigen assays versus complexed and free PSA assays and their ratios in discriminating between benign prostatic hyperplasia and prostate cancer. Author(s): Wians FH Jr, Cheli CD, Balko JA, Bruzek DJ, Chan DW, Sokoll LJ. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 2002 December; 326(1-2): 81-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12417099

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Evidence for activation of the renin-angiotensin system in the human prostate: increased angiotensin II and reduced AT(1) receptor expression in benign prostatic hyperplasia. Author(s): Dinh DT, Frauman AG, Somers GR, Ohishi M, Zhou J, Casley DJ, Johnston CI, Fabiani ME. Source: The Journal of Pathology. 2002 February; 196(2): 213-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11793373

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Expression of senescence-associated beta-galactosidase in enlarged prostates from men with benign prostatic hyperplasia. Author(s): Choi J, Shendrik I, Peacocke M, Peehl D, Buttyan R, Ikeguchi EF, Katz AE, Benson MC. Source: Urology. 2000 July; 56(1): 160-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10869659

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Expression of somatostatin receptor subtypes 2 and 4 in human benign prostatic hyperplasia and prostatic cancer. Author(s): Hansson J, Bjartell A, Gadaleanu V, Dizeyi N, Abrahamsson PA. Source: The Prostate. 2002 September 15; 53(1): 50-9. Erratum In: Prostate 2002 December 1; 53(4): 330. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12210479

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Factors related to delayed treatment and posttreatment symptom severity in Taiwanese patients with benign prostatic hyperplasia. Author(s): Chang CK, Yu HJ, Chan KW, Chie WC, Chen J, Chen YT, Lai MK. Source: J Formos Med Assoc. 1998 November; 97(11): 757-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9872032

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Familial aggregation of bothersome benign prostatic hyperplasia symptoms. Author(s): Pearson JD, Lei HH, Beaty TH, Wiley KE, Isaacs SD, Isaacs WB, Stoner E, Walsh PC. Source: Urology. 2003 April; 61(4): 781-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12670565

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Fatty acid composition of phospholipids in epithelium and stroma of human benign prostatic hyperplasia. Author(s): Weisser H, Krieg M. Source: The Prostate. 1998 September 1; 36(4): 235-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9719023

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FGF17 is an autocrine prostatic epithelial growth factor and is upregulated in benign prostatic hyperplasia. Author(s): Polnaszek N, Kwabi-Addo B, Wang J, Ittmann M. Source: The Prostate. 2004 June 15; 60(1): 18-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15129425

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FGF7 and FGF2 are increased in benign prostatic hyperplasia and are associated with increased proliferation. Author(s): Ropiquet F, Giri D, Lamb DJ, Ittmann M. Source: The Journal of Urology. 1999 August; 162(2): 595-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10411093

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Fibroblast growth factor receptor 1 (FGFR1) is over-expressed in benign prostatic hyperplasia whereas FGFR2-IIIc and FGFR3 are not. Author(s): Boget S, Cereser C, Parvaz P, Leriche A, Revol A. Source: European Journal of Endocrinology / European Federation of Endocrine Societies. 2001 September; 145(3): 303-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11517011

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Filling and voiding symptoms in the American Urological Association symptom index: the value of their distinction in a Veterans Affairs randomized trial of medical therapy in men with a clinical diagnosis of benign prostatic hyperplasia. Author(s): Barry MJ, Williford WO, Fowler FJ Jr, Jones KM, Lepor H. Source: The Journal of Urology. 2000 November; 164(5): 1559-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11025704

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Finasteride in benign prostatic hyperplasia. Author(s): Verhamme KM, Bosch RJ, Sturkenboom MC. Source: The New England Journal of Medicine. 2004 March 25; 350(13): 1359-61; Author Reply 1359-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15049034

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Finasteride in benign prostatic hyperplasia. Author(s): Wysowski DK, Farinas E. Source: The New England Journal of Medicine. 2004 March 25; 350(13): 1359-61; Author Reply 1359-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15044649

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Finasteride in the treatment of benign prostatic hyperplasia. Author(s): Ekman P, Andersen JT, Wolf H. Source: Acta Urol Belg. 1996 March; 64(1): Ix-Xii. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8659328

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Finasteride in the treatment of clinical benign prostatic hyperplasia: a systematic review of randomised trials. Author(s): Edwards JE, Moore RA. Source: Bmc Urology [electronic Resource]. 2002 December 12; 2(1): 14. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12477383

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Finasteride in the treatment of patients with moderate symptoms of benign prostatic hyperplasia. Author(s): Magoha GA. Source: East Afr Med J. 1998 May; 75(5): 260-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9746993

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Finasteride therapy does not alter bone turnover in men with benign prostatic hyperplasia--a Clinical Research Center study. Author(s): Tollin SR, Rosen HN, Zurowski K, Saltzman B, Zeind AJ, Berg S, Greenspan SL. Source: The Journal of Clinical Endocrinology and Metabolism. 1996 March; 81(3): 10314. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8772571

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Finasteride: a long-term follow-up in the treatment of recurrent hematuria associated with benign prostatic hyperplasia. Author(s): Delakas D, Lianos E, Karyotis I, Cranidis A. Source: Urologia Internationalis. 2001; 67(1): 69-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11464120

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Finasteride: an update of its use in the management of symptomatic benign prostatic hyperplasia. Author(s): Wilde MI, Goa KL. Source: Drugs. 1999 April; 57(4): 557-81. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10235693

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First dose efficacy of alfuzosin once daily in men with symptomatic benign prostatic hyperplasia. Author(s): Marks LS, Roehrborn CG, Gittelman M, Kim D, Forrest J, Jacobs S. Source: Urology. 2003 November; 62(5): 888-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14624914

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Free and complexed prostate specific antigen in the differentiation of benign prostatic hyperplasia and prostate cancer: studies in serum and plasma samples. Author(s): Espana F, Royo M, Martinez M, Enguidanos MJ, Vera CD, Estelles A, Aznar J, Jimenez-Cruz JF, Heeb MJ. Source: The Journal of Urology. 1998 December; 160(6 Pt 1): 2081-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9817329

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Functional and anatomical effects of hormonally induced experimental prostate growth: a urodynamic model of benign prostatic hyperplasia (BPH) in the beagle. Author(s): Yokota T, Honda K, Tsuruya Y, Nomiya M, Yamaguchi O, Gotanda K, Constantinou CE. Source: The Prostate. 2004 February 1; 58(2): 156-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14716740

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Gene expression signature of benign prostatic hyperplasia revealed by cDNA microarray analysis. Author(s): Luo J, Dunn T, Ewing C, Sauvageot J, Chen Y, Trent J, Isaacs W. Source: The Prostate. 2002 May 15; 51(3): 189-200. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11967953

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Genetic susceptibility of benign prostatic hyperplasia. Author(s): Sanda MG, Beaty TH, Stutzman RE, Childs B, Walsh PC. Source: The Journal of Urology. 1994 July; 152(1): 115-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7515446

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Genetic variations in human benign prostatic hyperplasia detected by restriction landmark genomic scanning. Author(s): Konishi N, Hiasa Y, Matsuda H, Nakamura M, Kitahori Y. Source: The Journal of Urology. 1997 April; 157(4): 1499-503. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9120990

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Getting ready for certification: benign prostatic hyperplasia. Author(s): Secrist J. Source: Urologic Nursing : Official Journal of the American Urological Association Allied. 2000 August; 20(4): 266. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11998090

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Glans hyperemia after penile revascularization: a late complication following alpha1-receptor blockade for benign prostatic hyperplasia. Author(s): Haupt G, Pannek J, Pastor J, Schulze H, Senge T. Source: Urologia Internationalis. 1997; 58(1): 61-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9058525

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Goals for benign prostatic hyperplasia therapy. Author(s): Lowe FC. Source: Urology. 2002 February; 59(2 Suppl 1): 1-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11832306

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Guidelines for the diagnosis and treatment of benign prostatic hyperplasia: a comparative, international overview. Author(s): Roehrborn CG, Bartsch G, Kirby R, Andriole G, Boyle P, de la Rosette J, Perrin P, Ramsey E, Nordling J, De Campos Freire G, Arap S. Source: Urology. 2001 November; 58(5): 642-50. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11711329

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Guidelines on benign prostatic hyperplasia: where do we stand in the new millennium? Author(s): Djavan B. Source: Curr Urol Rep. 2002 April; 3(2): 91-2. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12084198

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Haemodynamic changes detected during open prostatectomy and transurethral resection for benign prostatic hyperplasia. Author(s): D'Addessi A, Perilli V, Ranieri R, Sollazzi L, Crea MA, Racioppi M, Alcini A, Alcini E. Source: Scandinavian Journal of Urology and Nephrology. 1999 June; 33(3): 176-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10452293

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Heat versus drugs in the treatment of benign prostatic hyperplasia. Author(s): Djavan B, Seitz C, Marberger M. Source: Bju International. 2003 January; 91(2): 131-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12519114

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Heat versus drugs in the treatment of benign prostatic hyperplasia. Author(s): Bhanot S. Source: Bju International. 2003 July; 92(1): 152. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12823404

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Heat versus drugs in the treatment of benign prostatic hyperplasia. Author(s): Nawrocki J. Source: Bju International. 2003 May; 91(7): 732. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12699500

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Herbal medications in the treatment of benign prostatic hyperplasia (BPH). Author(s): Fagelman E, Lowe FC. Source: The Urologic Clinics of North America. 2002 February; 29(1): 23-9, Vii. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12109350

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Heritability of the symptoms of benign prostatic hyperplasia and the roles of age and zonal prostate volumes in twins. Author(s): Meikle AW, Bansal A, Murray DK, Stephenson RA, Middleton RG. Source: Urology. 1999 April; 53(4): 701-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10197844

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Heterogeneity of 5 alpha-reductase gene expression in benign prostatic hyperplasia. Author(s): Sherwood JB, McConnell JD, Vazquez DJ, Lin VK, Roehrborn CG. Source: The Journal of Urology. 2003 February; 169(2): 575-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12544310

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High intensity focused ultrasound in benign prostatic hyperplasia. Author(s): Hegarty NJ, Fitzpatrick JM. Source: European Journal of Ultrasound : Official Journal of the European Federation of Societies for Ultrasound in Medicine and Biology. 1999 March; 9(1): 55-60. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10099166

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High-energy microwave thermotherapy in the treatment of benign prostatic hyperplasia. Author(s): Cavarretta L, Scremin E, Cucciarre G, Todeschini M, Novella G, Tasca A. Source: Urologia Internationalis. 2003; 71(1): 10-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12845253

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High-energy transurethral microwave thermotherapy in patients with acute urinary retention due to benign prostatic hyperplasia. Author(s): Djavan B, Seitz C, Ghawidel K, Basharkhah A, Bursa B, Hruby S, Marberger M. Source: Urology. 1999 July; 54(1): 18-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10414720

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Histological changes of minimally invasive procedures for the treatment of benign prostatic hyperplasia and prostate cancer: clinical implications. Author(s): Larson BT, Bostwick DG, Corica AG, Larson TR. Source: The Journal of Urology. 2003 July; 170(1): 12-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12796636

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Histopathological aspects associated with the diagnosis of benign prostatic hyperplasia: clinical implications. Author(s): Sciarra A, Voria G, Mariotti G, Gentile V, Pastore A, Di Silverio F. Source: Urologia Internationalis. 2002; 69(4): 253-62. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12444279

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History of 7,093 patients with lower urinary tract symptoms related to benign prostatic hyperplasia treated with alfuzosin in general practice up to 3 years. Author(s): Lukacs B, Grange JC, Comet D, McCarthy C. Source: European Urology. 2000 February; 37(2): 183-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10705197

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Holmium and interstitial lasers for the treatment of benign prostatic hyperplasia: a laser revival. Author(s): Volpe MA, Fromer D, Kaplan SA. Source: Current Opinion in Urology. 2001 January; 11(1): 43-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11148745

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Holmium laser enucleation of the prostate combined with mechanical morcellation in 155 patients with benign prostatic hyperplasia. Author(s): Hurle R, Vavassori I, Piccinelli A, Manzetti A, Valenti S, Vismara A. Source: Urology. 2002 September; 60(3): 449-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12350482

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Human prostate cancer and benign prostatic hyperplasia: molecular dissection by gene expression profiling. Author(s): Luo J, Duggan DJ, Chen Y, Sauvageot J, Ewing CM, Bittner ML, Trent JM, Isaacs WB. Source: Cancer Research. 2001 June 15; 61(12): 4683-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11406537

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Hyperinsulinaemia as a risk factor for developing benign prostatic hyperplasia. Author(s): Hammarsten J, Hogstedt B. Source: European Urology. 2001 February; 39(2): 151-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11223674

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Hypertension in the elderly with coexisting benign prostatic hyperplasia. Author(s): Maruenda J, Bhatnagar V, Lowenthal DT. Source: Urology. 1999 March; 53(3 Suppl 3A): 7-12; Discussion 12-3, 41-2. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10094095

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Hyperthermia as a treatment modality in benign prostatic hyperplasia. Author(s): Matzkin H. Source: Urology. 1994 February; 43(2 Suppl): 17-20. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7509532

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Identification of a specifically expressed modified form of novel PSP-94 protein in the secretion of benign prostatic hyperplasia. Author(s): Xu K, Wang X, Ling MT, Lee DT, Fan T, Chan FL, Xuan JJ, Tsao SW, Wong YC. Source: Electrophoresis. 2003 April; 24(7-8): 1311-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12707925

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Identification of baseline clinical factors which predict medical treatment failure of benign prostatic hyperplasia: an observational cohort study. Author(s): Hong SJ, Ko WJ, Kim SI, Chung BH. Source: European Urology. 2003 July; 44(1): 94-9; Discussion 99-100. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12814681

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Improvements in benign prostatic hyperplasia-specific quality of life with dutasteride, the novel dual 5alpha-reductase inhibitor. Author(s): O'Leary MP, Roehrborn C, Andriole G, Nickel C, Boyle P, Hofner K. Source: Bju International. 2003 August; 92(3): 262-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12887480

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In vitro and in vivo evaluation of dihydropyrimidinone C-5 amides as potent and selective alpha(1A) receptor antagonists for the treatment of benign prostatic hyperplasia. Author(s): Barrow JC, Nantermet PG, Selnick HG, Glass KL, Rittle KE, Gilbert KF, Steele TG, Homnick CF, Freidinger RM, Ransom RW, Kling P, Reiss D, Broten TP, Schorn TW, Chang RS, O'Malley SS, Olah TV, Ellis JD, Barrish A, Kassahun K, Leppert P, Nagarathnam D, Forray C. Source: Journal of Medicinal Chemistry. 2000 July 13; 43(14): 2703-18. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10893308

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Incidence and prevalence of lower urinary tract symptoms suggestive of benign prostatic hyperplasia in primary care--the Triumph project. Author(s): Verhamme KM, Dieleman JP, Bleumink GS, van der Lei J, Sturkenboom MC, Artibani W, Begaud B, Berges R, Borkowski A, Chappel CR, Costello A, Dobronski P, Farmer RD, Jimenez Cruz F, Jonas U, MacRae K, Pientka L, Rutten FF, van Schayck CP, Speakman MJ, Sturkenboom MC, Tiellac P, Tubaro A, Vallencien G, Vela Navarrete R; Triumph Pan European Expert Panel. Source: European Urology. 2002 October; 42(4): 323-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12361895

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Incidence and risk reduction of long-term outcomes: a comparison of benign prostatic hyperplasia with several other disease areas. Author(s): Roehrborn CG, Dolte KS, Ross KS, Girman CJ. Source: Urology. 2000 July; 56(1): 9-18. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10869609

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Incidence and severity of sexual adverse experiences in finasteride and placebotreated men with benign prostatic hyperplasia. Author(s): Wessells H, Roy J, Bannow J, Grayhack J, Matsumoto AM, Tenover L, Herlihy R, Fitch W, Labasky R, Auerbach S, Parra R, Rajfer J, Culbertson J, Lee M, Bach MA, Waldstreicher J; PLESS Study Group. Source: Urology. 2003 March; 61(3): 579-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12639651

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Increased bladder apoptosis with alpha-1 adrenoceptor antagonists in benign prostatic hyperplasia. Author(s): Erdogru T, Gulkesen KH, Kukul E, Yalcinkaya M, Karpuzoglu G, Baykara M. Source: Scandinavian Journal of Urology and Nephrology. 2002; 36(3): 188-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12201933

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Increased discrimination between benign prostatic hyperplasia and prostate cancer with equimolar total prostate specific antigen measurement. Author(s): Onur R, Ilhan N, Orhan I, Ilhan N. Source: World Journal of Urology. 2003 May; 21(1): 43-7. Epub 2003 March 26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12756494

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Increased risk of prostate cancer and benign prostatic hyperplasia associated with transforming growth factor-beta 1 gene polymorphism at codon10. Author(s): Li Z, Habuchi T, Tsuchiya N, Mitsumori K, Wang L, Ohyama C, Sato K, Kamoto T, Ogawa O, Kato T. Source: Carcinogenesis. 2004 February; 25(2): 237-40. Epub 2003 November 06. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14604900

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Indwelling catheter treatment and health-related quality of life in men with prostate cancer in comparison with men with benign prostatic hyperplasia. Author(s): Jakobsson L. Source: Scandinavian Journal of Caring Sciences. 2002 September; 16(3): 264-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12191038

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Influence of bladder outlet obstruction and detrusor contractility on residual urine in patients with benign prostatic hyperplasia. Author(s): Zhang P, Wu Z, Gao J. Source: Chinese Medical Journal. 2003 October; 116(10): 1508-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14570611

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Influence of hypertension on lower urinary tract symptoms in benign prostatic hyperplasia. Author(s): Sugaya K, Kadekawa K, Ikehara A, Nakayama T, Gakiya M, Nashiro F, Goya M, Hatano T, Ogawa Y. Source: International Journal of Urology : Official Journal of the Japanese Urological Association. 2003 November; 10(11): 569-74; Discussion 575. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14633079

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Infrared microspectroscopic detection of epithelial and stromal growth in the human benign prostatic hyperplasia. Author(s): Li MJ, Hsu HS, Liang RC, Lin SY. Source: Ultrastructural Pathology. 2002 November-December; 26(6): 365-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12537761

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Insulin-like growth factor I, insulin-like growth factor binding protein 3, and urologic measures of benign prostatic hyperplasia. Author(s): Roberts RO, Jacobson DJ, Girman CJ, Rhodes T, Klee GG, Lieber MM, Jacobsen SJ. Source: American Journal of Epidemiology. 2003 May 1; 157(9): 784-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12727672

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Interleukin-1alpha is a paracrine inducer of FGF7, a key epithelial growth factor in benign prostatic hyperplasia. Author(s): Giri D, Ittmann M. Source: American Journal of Pathology. 2000 July; 157(1): 249-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10880394

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Interstitial laser coagulation combined with minimal transurethral resection of the prostate for the treatment of benign prostatic hyperplasia. Author(s): Corvin S, Schneede P, Siakavara E, Frimberger D, Zaak D, Siebels M, Reich O, Hofstetter A. Source: Journal of Endourology / Endourological Society. 2002 August; 16(6): 387-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12227915

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Interstitial laser coagulation treatment of benign prostatic hyperplasia: is it to be recommended? Author(s): Laguna MP, Alivizatos G, De La Rosette JJ. Source: Journal of Endourology / Endourological Society. 2003 October; 17(8): 595-600. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14622478

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Investigation of benign prostatic hyperplasia. Author(s): Tubaro A, Trucchi A, Miano L. Source: Current Opinion in Urology. 2003 January; 13(1): 17-22. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12490811

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Is the higher prevalence of benign prostatic hyperplasia related to lower urinary tract symptoms in Korean men due to a high transition zone index? Author(s): Am Fam Physician. 2002 Jul 1;66(1):87-8 Source: European Urology. 2002 July; 42(1): 7-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12126035

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KAI1/CD82 gene expression in benign prostatic hyperplasia and late-stage prostate cancer in Chinese. Author(s): Hu WL, Li YQ, He HX, Li QR, Tian Y, Lai RQ, Mei H. Source: Asian Journal of Andrology. 2000 September; 2(3): 221-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11225981

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Key questions in benign prostatic hyperplasia. Author(s): Neal DE, Hegarty P. Source: The Practitioner. 2003 November; 247(1652): 886-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14640052

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Kinetics of acetyl coenzyme A: arylamine N-acetyltransferase from rapid and slow acetylator human benign prostatic hyperplasia tissues. Author(s): Yeh CC, Hung CF, Wang WL, Chung JG. Source: Urological Research. 2001 October; 29(5): 311-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11764764

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Laparoscopic prostatectomy with vascular control for benign prostatic hyperplasia. Author(s): Mariano MB, Graziottin TM, Tefilli MV. Source: The Journal of Urology. 2002 June; 167(6): 2528-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11992078

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Large benign prostatic hyperplasia means impossible ureteroscopy: myth or reality? Author(s): Scarpa RM, De Lisa A, Porru D, Usai E. Source: European Urology. 2000 April; 37(4): 381-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10765066

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Laser ablation of the prostate versus transurethral resection of the prostate in men with benign prostatic hyperplasia. Author(s): Chahal R, Sundaram SK. Source: Urology. 2000 September 1; 56(3): 546-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11001643

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Laser therapy for benign prostatic hyperplasia: a review of recent developments. Author(s): Aho TF, Gilling PJ. Source: Current Opinion in Urology. 2003 January; 13(1): 39-44. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12490814

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Leptin in relation to prostate cancer and benign prostatic hyperplasia. Author(s): Lagiou P, Signorello LB, Trichopoulos D, Tzonou A, Trichopoulou A, Mantzoros CS. Source: International Journal of Cancer. Journal International Du Cancer. 1998 March 30; 76(1): 25-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9533757

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Localization of angiotensin-converting enzyme in the human prostate: pathological expression in benign prostatic hyperplasia. Author(s): Nassis L, Frauman AG, Ohishi M, Zhuo J, Casley DJ, Johnston CI, Fabiani ME. Source: The Journal of Pathology. 2001 December; 195(5): 571-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11745693

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Long-term (4 year) efficacy and tolerability of doxazosin for the treatment of concurrent benign prostatic hyperplasia and hypertension. Author(s): Fawzy A, Hendry A, Cook E, Gonzalez F. Source: International Journal of Urology : Official Journal of the Japanese Urological Association. 1999 July; 6(7): 346-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10445304

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Long-term (7 to 8-year) experience with finasteride in men with benign prostatic hyperplasia. Author(s): Vaughan D, Imperato-McGinley J, McConnell J, Matsumoto AM, Bracken B, Roy J, Sullivan M, Pappas F, Cook T, Daurio C, Meehan A, Stoner E, Waldstreicher J. Source: Urology. 2002 December; 60(6): 1040-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12475666

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Long-term 6-year experience with finasteride in patients with benign prostatic hyperplasia. Author(s): Lowe FC, McConnell JD, Hudson PB, Romas NA, Boake R, Lieber M, Elhilali M, Geller J, Imperto-McGinely J, Andriole GL, Bruskewitz RC, Walsh PC, Bartsch G, Nacey JN, Shah S, Pappas F, Ko A, Cook T, Stoner E, Waldstreicher J; Finasteride Study Group. Source: Urology. 2003 April; 61(4): 791-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12670567

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Long-term effects of finasteride in patients with benign prostatic hyperplasia: a double-blind, placebo-controlled, multicenter study. PROWESS Study Group. Author(s): Marberger MJ. Source: Urology. 1998 May; 51(5): 677-86. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9610579

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Long-term evaluation of transurethral needle ablation of the prostate (TUNA) for treatment of symptomatic benign prostatic hyperplasia: clinical outcome up to five years from three centers. Author(s): Zlotta AR, Giannakopoulos X, Maehlum O, Ostrem T, Schulman CC. Source: European Urology. 2003 July; 44(1): 89-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12814680

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Long-term incidence of acute myocardial infarction after open and transurethral resection of the prostate for benign prostatic hyperplasia. Author(s): Shalev M, Richter S, Kessler O, Shpitz B, Fredman B, Nissenkorn I. Source: The Journal of Urology. 1999 February; 161(2): 491-3. Erratum In: 1999 April; 161(4): 1287. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9915433

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Long-term outcome of transrectal high- intensity focused ultrasound therapy for benign prostatic hyperplasia. Author(s): Madersbacher S, Schatzl G, Djavan B, Stulnig T, Marberger M. Source: European Urology. 2000 June; 37(6): 687-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10828669

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Long-term results of contact laser versus transurethral resection of the prostate in the treatment of benign prostatic hyperplasia with small or moderately enlarged prostates. Author(s): Tuhkanen K, Heino A, Aaltomaa S, Ala-Opas M. Source: Scandinavian Journal of Urology and Nephrology. 2003; 37(6): 487-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14675922

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Long-term safety and efficacy of a once-daily formulation of alfuzosin 10 mg in patients with symptomatic benign prostatic hyperplasia: open-label extension study. Author(s): van Kerrebroec P, Jardin A, van Cangh P, Laval KU; ALFORTI Study Group. Source: European Urology. 2002 January; 41(1): 54-60; Discussion 60-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11999466

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Long-term safety and efficacy of tamsulosin for the treatment of lower urinary tract symptoms associated with benign prostatic hyperplasia. Author(s): Narayan P, Evans CP, Moon T. Source: The Journal of Urology. 2003 August; 170(2 Pt 1): 498-502. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12853808

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Long-term treatment with finasteride in men with symptomatic benign prostatic hyperplasia: 10-year follow-up. Author(s): Lam JS, Romas NA, Lowe FC. Source: Urology. 2003 February; 61(2): 354-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12597947

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Long-term, open-label, phase III multicenter study of tamsulosin in benign prostatic hyperplasia. Author(s): Narayan P, Lepor H. Source: Urology. 2001 March; 57(3): 466-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11248621

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Lower-energy thermotherapy in the treatment of benign prostatic hyperplasia: longterm follow-up results of a multicenter international study. Author(s): Francisca EA, Keijzers GB, d'Ancona FC, Debruyne FM, de la Rosette JJ. Source: World Journal of Urology. 1999 October; 17(5): 279-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10552144

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Management of acute urinary retention secondary to benign prostatic hyperplasia in the UK: a national survey. Author(s): Manikandan R, Srirangam SJ, O'Reilly PH, Collins GN. Source: Bju International. 2004 January; 93(1): 84-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14678374

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Management of symptomatic benign prostatic hyperplasia in southern Italy: a retrospective analysis of the Sicilian-Calabrian Society of Urology (SSCU) of 32,000 patients. Author(s): Serretta V, Morgia G, Fondacaro L, Curto G, Pirritano D, Lo Bianco A, Melloni D, Orestano F, Motta M, Pavone-Macaluso M; Members of the SicilianCalabrian Society of Urology. Source: Urologia Internationalis. 2003; 71(1): 16-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12845254

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Medical management of benign prostatic hyperplasia--are two drugs better than one? Author(s): Vaughan ED Jr. Source: The New England Journal of Medicine. 2003 December 18; 349(25): 2449-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14681512

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Medical therapy for asymptomatic men with benign prostatic hyperplasia: primum non nocere. Author(s): Kaplan SA. Source: Urology. 2003 November; 62(5): 784-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14624894

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Medical therapy for benign prostatic hyperplasia progression. Author(s): McVary KT. Source: Curr Urol Rep. 2002 August; 3(4): 269-75. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12149154

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Medical therapy for benign prostatic hyperplasia: a review of the literature. Author(s): Clifford GM, Farmer RD. Source: European Urology. 2000 July; 38(1): 2-19. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10859436

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Medical therapy for benign prostatic hyperplasia: sexual dysfunction and impact on quality of life. Author(s): Carbone DJ Jr, Hodges S. Source: International Journal of Impotence Research : Official Journal of the International Society for Impotence Research. 2003 August; 15(4): 299-306. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12934061

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Messenger RNA levels and enzyme activities of 5 alpha-reductase types 1 and 2 in human benign prostatic hyperplasia (BPH) tissue. Author(s): Shirakawa T, Okada H, Acharya B, Zhang Z, Hinata N, Wada Y, Uji T, Kamidono S, Gotoh A. Source: The Prostate. 2004 January 1; 58(1): 33-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14673950

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Minimal transurethral prostatectomy plus bladder neck incision versus standard transurethral prostatectomy in patients with benign prostatic hyperplasia: a randomised prospective study. Author(s): Yeni E, Unal D, Verit A, Gulum M. Source: Urologia Internationalis. 2002; 69(4): 283-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12444284

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Minimally invasive therapies for benign prostatic hyperplasia. Author(s): Tunuguntla HS, Evans CP. Source: World Journal of Urology. 2002 September; 20(4): 197-206. Epub 2002 June 15. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12215846

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Molecular and cellular prostate biology: origin of prostate-specific antigen expression and implications for benign prostatic hyperplasia. Author(s): Schalken JA. Source: Bju International. 2004 March; 93 Suppl 1: 5-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15009079

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Natural history and epidemiology of benign prostatic hyperplasia: relationship among urologic measures. Author(s): Girman CJ. Source: Urology. 1998 April; 51(4A Suppl): 8-12. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9586590

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Natural history of benign prostatic hyperplasia. Author(s): Jacobsen SJ, Girman CJ, Lieber MM. Source: Urology. 2001 December; 58(6 Suppl 1): 5-16; Discussion 16. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11750242

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Neoadjuvant and adjuvant alpha-blockade improves early results of high-energy transurethral microwave thermotherapy for lower urinary tract symptoms of benign prostatic hyperplasia: a randomized, prospective clinical trial. Author(s): Djavan B, Shariat S, Fakhari M, Ghawidel K, Seitz C, Partin AW, Roehrborn CG, Marberger M. Source: Urology. 1999 February; 53(2): 251-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9933035

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Neuroendocrine cells in benign prostatic hyperplasia and prostatic carcinoma: effect of hormonal treatment. Author(s): Guate JL, Escaf S, Menendez CL, del Valle M, Vega JA. Source: Urologia Internationalis. 1997; 59(3): 149-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9428430

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New concepts in tissue specificity for prostate cancer and benign prostatic hyperplasia. Author(s): De Marzo AM, Coffey DS, Nelson WG. Source: Urology. 1999 March; 53(3 Suppl 3A): 29-39; Discussion 39-42. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10094098

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Nitric oxide based influence of nitrates on micturition in patients with benign prostatic hyperplasia. Author(s): Klotz T, Mathers MJ, Bloch W, Nayal W, Engelmann U. Source: International Urology and Nephrology. 1999; 31(3): 335-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10672953

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Nocturia and benign prostatic hyperplasia. Author(s): Yoshimura K, Ohara H, Ichioka K, Terada N, Matsui Y, Terai A, Arai Y. Source: Urology. 2003 April; 61(4): 786-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12670566

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Nonsurgical management of benign prostatic hyperplasia in men with bladder calculi. Author(s): O'Connor RC, Laven BA, Bales GT, Gerber GS. Source: Urology. 2002 August; 60(2): 288-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12137828

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Novel thiophene derivatives for the treatment of benign prostatic hyperplasia. Author(s): Khatuya H, Pulito VL, Jolliffe LK, Li X, Murray WV. Source: Bioorganic & Medicinal Chemistry Letters. 2002 August 19; 12(16): 2145-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12127524

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Obesity in relation to prostate cancer risk: comparison with a population having benign prostatic hyperplasia. Author(s): Irani J, Lefebvre O, Murat F, Dahmani L, Dore B. Source: Bju International. 2003 April; 91(6): 482-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12656898

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Observational multicentric trial performed with doxazosin: evaluation of sexual effects on patients with diagnosed benign prostatic hyperplasia. Author(s): De Rose AF, Carmignani G, Corbu C, Giglio M, Traverso P, Naselli A, Belgrano E, Catuogno C, Fontana D, Maver A, Mirone V, Muzzonigro G, Di Trapani D, Bonini F. Source: Urologia Internationalis. 2002; 68(2): 95-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11834898

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Obstructive benign prostatic hyperplasia: therapeutical aspects. Author(s): Altwein JE. Source: European Urology. 1998; 34 Suppl 1: 31-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9705552

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On the prediction of the histologic composition of benign prostatic hyperplasia based on clinical and MRI parameters. Author(s): Weijers RE, Zambon JV, Kessels AG, de Bruine AP. Source: The Prostate. 1997 August 1; 32(3): 179-87. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9254897

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Open prostatectomy in benign prostatic hyperplasia: 10-year experience in Italy. Author(s): Mearini E, Marzi M, Mearini L, Zucchi A, Porena M. Source: European Urology. 1998 December; 34(6): 480-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9831789

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Osteopontin expression in prostate cancer and benign prostatic hyperplasia. Author(s): Tozawa K, Yamada Y, Kawai N, Okamura T, Ueda K, Kohri K. Source: Urologia Internationalis. 1999; 62(3): 155-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10529666

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Our experience with the treatment of benign prostatic hyperplasia (BPH) with tamsulosin. Author(s): Cervenakov I, Fillo J. Source: Bratisl Lek Listy. 2001; 102(3): 138-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11433602

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Outcome analysis of minimally invasive treatments for benign prostatic hyperplasia. Author(s): Djavan B, Madersbacher S, Klingler HC, Ghawidel K, Basharkhah A, Hruby S, Seitz C, Marberger M. Source: Tech Urol. 1999 March; 5(1): 12-20. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10374789

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Over-expression of epidermal growth factor receptor and c-erbB2/neu but not of int-2 genes in benign prostatic hyperplasia by means of semi-quantitative PCR. Author(s): Schwartz S Jr, Caceres C, Morote J, De Torres I, Rodriguez-Vallejo JM, Gonzalez J, Reventos J. Source: International Journal of Cancer. Journal International Du Cancer. 1998 May 18; 76(4): 464-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9590118

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Overview of alpha-blocker therapy for benign prostatic hyperplasia. Author(s): Narayan P, Tewari A. Source: Urology. 1998 April; 51(4A Suppl): 38-45. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9586595

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Photoselective vaporization of the prostate: initial experience with a new 80 W KTP laser for the treatment of benign prostatic hyperplasia. Author(s): Hai MA, Malek RS. Source: Journal of Endourology / Endourological Society. 2003 March; 17(2): 93-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12689402

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Positive response to ice water test associated with high-grade bladder outlet obstruction in patients with benign prostatic hyperplasia. Author(s): Hirayama A, Fujimoto K, Matsumoto Y, Ozono S, Hirao Y. Source: Urology. 2003 November; 62(5): 909-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14624918

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Pro-apoptotic tumor necrosis factor-alpha transduction pathway in normal prostate, benign prostatic hyperplasia and prostatic carcinoma. Author(s): Ricote M, Royuela M, Garcia-Tunon I, Bethencourt FR, Paniagua R, Fraile B. Source: The Journal of Urology. 2003 September; 170(3): 787-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12913698

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Prostate carcinoma risk subsequent to diagnosis of benign prostatic hyperplasia: a population-based cohort study in Sweden. Author(s): Chokkalingam AP, Nyren O, Johansson JE, Gridley G, McLaughlin JK, Adami HO, Hsing AW. Source: Cancer. 2003 October 15; 98(8): 1727-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14534890

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Prostate-specific antigen and transition zone index - powerful predictors for acute urinary retention in men with benign prostatic hyperplasia. Author(s): Milonas D, Trumbeckas D. Source: Medicina (Kaunas, Lithuania). 2003; 39(11): 1071-7. English, Lithuanian. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14646460

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Prostate-specific antigen as an estimator of prostate volume in the management of patients with symptomatic benign prostatic hyperplasia. Author(s): Mochtar CA, Kiemeney LA, van Riemsdijk MM, Barnett GS, Laguna MP, Debruyne FM, de la Rosette JJ. Source: European Urology. 2003 December; 44(6): 695-700. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14644122

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Prostate-specific antigen levels and density in the internal and external glands of the prostate in benign prostatic hyperplasia patients with normal or gray-zone PSA levels. Author(s): Zuo W, Hiraoka Y. Source: Urologia Internationalis. 2003; 71(2): 154-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12890952

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Prostate-specific antigen, prostate volume and transition zone volume in Japanese patients with histologically proven benign prostatic hyperplasia. Author(s): Furuya Y, Ohta S, Sato N, Kotake T, Masai M. Source: International Urology and Nephrology. 2001; 33(4): 645-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12452619

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Prostatic tissual distribution of alfuzosin in patients with benign prostatic hyperplasia following repeated oral administration. Author(s): Mottet N, Bressolle F, Delmas V, Robert M, Costa P. Source: European Urology. 2003 July; 44(1): 101-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12814682

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Quality of life of patients on the waiting list for benign prostatic hyperplasia surgery. Author(s): Salinas-Sanchez AS, Hernandez-Millan I, Lorenzo-Romero JG, Segura-Martin M, Fernandez-Olano C, Virseda-Rodriguez JA. Source: Quality of Life Research : an International Journal of Quality of Life Aspects of Treatment, Care and Rehabilitation. 2001; 10(6): 543-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11789554

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Quality of life, voiding symptoms and uroflowmetry in healthy males and benign prostatic hyperplasia (BPH) patients. Author(s): Batista JE, Regalado R, Arano P, Vicente J. Source: J Urol (Paris). 1995; 101(1): 3-6. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7545724

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Quality-of-life aspects in urology - benign prostatic hyperplasia. Author(s): MacDonagh R, Pearcy R. Source: World Journal of Urology. 1999 August; 17(4): 199-204. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10460401

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Quality-of-life assessment in patients with benign prostatic hyperplasia: effects of various interventions. Author(s): Batista-Miranda JE, Diez MD, Bertran PA, Villavicencio H. Source: Pharmacoeconomics. 2001; 19(11): 1079-90. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11735675

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Quantitation of potentially undiagnosed incidental carcinoma of the prostate in patients treated non-surgically for benign prostatic hyperplasia. Author(s): Anderson GA, Lawson RK, Gottlieb MS. Source: British Journal of Urology. 1993 October; 72(4): 465-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7505190

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Questioning questions about symptoms of benign prostatic hyperplasia. Author(s): Hassler E, Krakau I, Haggarth L, Norlen L, Ekman P. Source: Family Practice. 2001 June; 18(3): 328-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11356743

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Randomized clinical trial comparing transurethral needle ablation with transurethral resection of the prostate for the treatment of benign prostatic hyperplasia: results at 18 months. Author(s): Cimentepe E, Unsal A, Saglam R. Source: Journal of Endourology / Endourological Society. 2003 March; 17(2): 103-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12689404

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Re: histological changes of minimally invasive procedures for the treatment of benign prostatic hyperplasia and prostate cancer: clinical implications. Author(s): Kumar H. Source: The Journal of Urology. 2004 March; 171(3): 1244. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14767319

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Real life practice in the management of benign prostatic hyperplasia. Author(s): Naderi N, Mochtar CA, de la Rosette JJ. Source: Current Opinion in Urology. 2004 January; 14(1): 41-4. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15091049

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Recent trends in mortality from benign prostatic hyperplasia. Author(s): Levi F, Lucchini F, Negri E, Boyle P, La Vecchia C. Source: The Prostate. 2003 August 1; 56(3): 207-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12772190

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Regulation of stromal proliferation, growth arrest, differentiation and apoptosis in benign prostatic hyperplasia by TGF-beta. Author(s): Huang X, Lee C. Source: Frontiers in Bioscience : a Journal and Virtual Library. 2003 September 1; 8: S7409. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12957826

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Relationship between benign prostatic hyperplasia and history of coronary artery disease in elderly men. Author(s): Weisman KM, Larijani GE, Goldstein MR, Goldberg ME. Source: Pharmacotherapy. 2000 April; 20(4): 383-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10772367

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Relationship between Prostatic Specific Antigen (PSA) and volume of the prostate in the Benign Prostatic Hyperplasia in the elderly. Author(s): Bo M, Ventura M, Marinello R, Capello S, Casetta G, Fabris F. Source: Critical Reviews in Oncology/Hematology. 2003 September; 47(3): 207-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12962896

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Relief by botulinum toxin of voiding dysfunction due to benign prostatic hyperplasia: results of a randomized, placebo-controlled study. Author(s): Maria G, Brisinda G, Civello IM, Bentivoglio AR, Sganga G, Albanese A. Source: Urology. 2003 August; 62(2): 259-64; Discussion 264-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12893330

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Relief of benign prostatic hyperplasia-related bladder outlet obstruction after transarterial polyvinyl alcohol prostate embolization. Author(s): DeMeritt JS, Elmasri FF, Esposito MP, Rosenberg GS. Source: Journal of Vascular and Interventional Radiology : Jvir. 2000 June; 11(6): 767-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10877424

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Safety and efficacy of sustained-release alfuzosin on lower urinary tract symptoms suggestive of benign prostatic hyperplasia in 3,095 Spanish patients evaluated during general practice. Author(s): Sanchez-Chapado M, Guil M, Alfaro V, Badiella L, Fernandez-Hernando N. Source: European Urology. 2000 April; 37(4): 421-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10765072

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Serum concentrations of sex hormones in men with severe lower urinary tract symptoms and benign prostatic hyperplasia. Author(s): Tan MO, Karabiyik I, Uygur MC, Diker Y, Erol D. Source: International Urology and Nephrology. 2003; 35(3): 357-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15160539

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Serum human glandular kallikrein (hK2) and insulin-like growth factor 1 (IGF-1) improve the discrimination between prostate cancer and benign prostatic hyperplasia in combination with total and %free PSA. Author(s): Scorilas A, Plebani M, Mazza S, Basso D, Soosaipillai AR, Katsaros N, Pagano F, Diamandis EP. Source: The Prostate. 2003 February 15; 54(3): 220-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12518327

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Serum prostate specific antigen levels in men with benign prostatic hyperplasia and cancer of prostate. Author(s): Amayo A, Obara W. Source: East Afr Med J. 2004 January; 81(1): 22-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15080511

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Serum triiodothyronine is increased in men with prostate cancer and benign prostatic hyperplasia. Author(s): Lehrer S, Diamond EJ, Stone NN, Droller MJ, Stock RG. Source: The Journal of Urology. 2002 December; 168(6): 2431-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12441933

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Sexual function in 131 patients with benign prostatic hyperplasia before prostatectomy. Author(s): Baniel J, Israilov S, Shmueli J, Segenreich E, Livne PM. Source: European Urology. 2000 July; 38(1): 53-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10859442

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Sexual function in patients treated for benign prostatic hyperplasia. Author(s): Kassabian VS. Source: Lancet. 2003 January 4; 361(9351): 60-2. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12517472

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Strong effects of definition and nonresponse bias on prevalence rates of clinical benign prostatic hyperplasia: the Krimpen study of male urogenital tract problems and general health status. Author(s): Blanker MH, Groeneveld FP, Prins A, Bernsen RM, Bohnen AM, Bosch JL. Source: Bju International. 2000 April; 85(6): 665-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10759662

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Study of detrusor dysfunction due to outlet obstruction: link between analysis of uroflows of men with benign prostatic hyperplasia and animal studies. Author(s): Valentini FA, Levin RM, Besson GR, Nelson PP. Source: Advances in Experimental Medicine and Biology. 2003; 539(Pt A): 297-309. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15088913

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Tamsulosin for benign prostatic hyperplasia. Author(s): Wilt TJ, Mac Donald R, Rutks I. Source: Cochrane Database Syst Rev. 2003; (1): Cd002081. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12535426

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Terazosin for benign prostatic hyperplasia. Author(s): Wilt TJ, Howe RW, Rutks IR, MacDonald R. Source: Cochrane Database Syst Rev. 2002; (4): Cd003851. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12519611

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The development and preliminary evaluation of a decision aid based on decision analysis for two treatment conditions: benign prostatic hyperplasia and hypertension. Author(s): Dowding D, Swanson V, Bland R, Thomson P, Mair C, Morrison A, Taylor A, Beechey C, Simpson R, Niven K. Source: Patient Education and Counseling. 2004 February; 52(2): 209-15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15132527

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The efficacy of an abbreviated model of the International Prostate Symptom Score in evaluating benign prostatic hyperplasia. Author(s): Cam K, Senel F, Akman Y, Erol A. Source: Bju International. 2003 February; 91(3): 186-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12581001

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The pathophysiology of benign prostatic hyperplasia. Author(s): Djavan B, Remzi M, Erne B, Marberger M. Source: Drugs Today (Barc). 2002 December; 38(12): 867-76. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12582474

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Thermotherapy and thermoablation for benign prostatic hyperplasia. Author(s): Gravas S, Laguna P, de la Rosette J. Source: Current Opinion in Urology. 2003 January; 13(1): 45-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12490815

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Transcutaneous electrovesicogram in normal volunteers and patients with interstitial cystitis, neurogenic bladder, benign prostatic hyperplasia, and after cystectomy. Author(s): Shafik A. Source: Advances in Experimental Medicine and Biology. 2003; 539(Pt A): 441-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15088921

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Transurethral hot-water balloon thermoablation for benign prostatic hyperplasia: patient tolerance and pathologic findings. Author(s): Corica FA, Cheng L, Ramnani D, Pacelli A, Weaver A, Corica AP, Corica AG, Larson TR, O'Toole K, Bostwick DG. Source: Urology. 2000 July; 56(1): 76-80; Discussion 81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10869628

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Treatment of benign prostatic hyperplasia with transurethral electrovaporization of the prostate (TUVP) using Vaportrode VE-B. Two years follow-up. Author(s): Diana M, Schettini M, Gallucci M. Source: Minerva Urol Nefrol. 1999 December; 51(4): 191-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10812903

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Ultrasonic measurement of bladder weight as a possible predictor of acute urinary retention in men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia. Author(s): Miyashita H, Kojima M, Miki T. Source: Ultrasound in Medicine & Biology. 2002 August; 28(8): 985-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12217433

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Ultrastructural and biophysical studies on protein conformations of epithelium and stroma in benign prostatic hyperplasia before and after transurethral resection of the prostate. Author(s): Hsu HS, Lin SY, Li MJ, Liang RC. Source: Ultrastructural Pathology. 2002 May-June; 26(3): 137-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12184371

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Update on the medical management of benign prostatic hyperplasia. Author(s): Monga M. Source: International Urology and Nephrology. 2002; 33(1): 67-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12090341

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Up-regulation of hepatic IGFBP-1 production as a strategy for preventing benign prostatic hyperplasia. Author(s): McCarty MF. Source: Medical Hypotheses. 2001 January; 56(1): 1-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11133245

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Urethral resistance factor (URA) versus Schafer's obstruction grade and AbramsGriffiths (AG) number in the diagnosis of obstructive benign prostatic hyperplasia. Author(s): Eckhardt MD, van Venrooij GE, Boon TA. Source: Neurourology and Urodynamics. 2001; 20(2): 175-85. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11170192

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Urodynamic and clinical effects of terazosin therapy in patients with symptomatic benign prostatic hyperplasia. Author(s): Witjes WP, Rosier FW, de Wildt MJ, van Iersel MP, Debruyne FM, de La Rosette JJ. Source: The Journal of Urology. 1996 April; 155(4): 1317-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8632523

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Urodynamic effects of terazosin treatment for Japanese patients with symptomatic benign prostatic hyperplasia. Author(s): Tanaka Y, Masumori N, Itoh N, Sato Y, Takahashi A, Ogura H, Furuya S, Tsukamoto T. Source: The Journal of Urology. 2002 June; 167(6): 2492-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11992065

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Usefulness of a prevoiding transabdominal sonographic bladder scan for uroflowmetry in patients involved in clinical studies of benign prostatic hyperplasia. Author(s): Dicuio M, Creti S, Di Campli A, Dipietro R, Mannini D, Nanni G, Dahlstrand C, Cuzzocrea DE. Source: Journal of Ultrasound in Medicine : Official Journal of the American Institute of Ultrasound in Medicine. 2003 August; 22(8): 773-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12901403

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Usefulness of tamsulosin hydrochloride and naftopidil in patients with urinary disturbances caused by benign prostatic hyperplasia: a comparative, randomized, two-drug crossover study. Author(s): Ikemoto I, Kiyota H, Ohishi Y, Abe K, Goto H, Kishimoto K, Miki K. Source: International Journal of Urology : Official Journal of the Japanese Urological Association. 2003 November; 10(11): 587-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14633083

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Validation of the self-administered Danish Prostatic Symptom Score (DAN-PSS-1) system for use in benign prostatic hyperplasia. Author(s): Hansen BJ, Flyger H, Brasso K, Schou J, Nordling J, Thorup Andersen J, Mortensen S, Meyhoff HH, Walter S, Hald T. Source: British Journal of Urology. 1995 October; 76(4): 451-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7551880

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Value of prostatic cancer screening in patients treated for benign prostatic hyperplasia with medical or minimally invasive modalities. Author(s): Orihuela E, Kocurek JN, Warren MM. Source: Arch Esp Urol. 1997 September; 50(7): 821-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9350090

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Value of the Danish Prostate Symptom Score compared to the AUA symptom score and pressure/flow studies in the preoperative evaluation of men with symptomatic benign prostatic hyperplasia. Author(s): Pannek J, Berges RR, Haupt G, Senge T. Source: Neurourology and Urodynamics. 1998; 17(1): 9-18. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9453687

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Variability of pressure-flow analysis parameters in repeated cystometry in patients with benign prostatic hyperplasia. Author(s): Rosier PF, de la Rosette JJ, Koldewijn EL, Debruyne FM, Wijkstra H. Source: The Journal of Urology. 1995 May; 153(5): 1520-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7536260

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Variations of transition zone volume and transition zone index after transurethral needle ablation for symptomatic benign prostatic hyperplasia. Author(s): Fujimoto K, Hosokawa Y, Tomioka A, Yamamoto H, Tanaka Y, Otani T, Ozono S, Hirao Y, Hayashi Y. Source: International Journal of Urology : Official Journal of the Japanese Urological Association. 2003 July; 10(7): 392-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12823695

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Vascular endothelial growth factor (VEGF) expression in prostate cancer and benign prostatic hyperplasia. Author(s): Jackson MW, Bentel JM, Tilley WD. Source: The Journal of Urology. 1997 June; 157(6): 2323-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9146664

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Visual laser ablation of the prostate (VLAP): an effective alternative treatment of benign prostatic hyperplasia. Author(s): Mattelaer P, Jung P, Wolff J, Jakse G. Source: Acta Urol Belg. 1995 September; 63(3): 45-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7484522

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Voiding dysfunction in benign prostatic hyperplasia: trends, controversies and recent revelations. I. Symptoms and urodynamics. Author(s): Elbadawi A. Source: Urology. 1998 May; 51(5A Suppl): 62-72. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9610560

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Voiding dysfunction in benign prostatic hyperplasia: trends, controversies and recent revelations. II. Pathology and pathophysiology. Author(s): Elbadawi A. Source: Urology. 1998 May; 51(5A Suppl): 73-82. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9610561

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Volume determinations by transrectal ultrasonography in patients with benign prostatic hyperplasia: correlation with removed prostate weight. Author(s): Alkan I, Turkeri L, Biren T, Cevik I, Akdas A. Source: International Urology and Nephrology. 1996; 28(4): 517-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9119637

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Watchful waiting encouraged for benign prostatic hyperplasia. Author(s): Daze CJ. Source: Manag Care. 1994 May; 3(5): 49-50. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10146142

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Watchful waiting or drug therapy for benign prostatic hyperplasia? Author(s): Neal DE. Source: Lancet. 1997 August 2; 350(9074): 305-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9251630

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Water-induced thermotherapy for benign prostatic hyperplasia. Author(s): Cioanta I, Muschter R. Source: Tech Urol. 2000 December; 6(4): 294-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11108569

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When to investigate benign prostatic hyperplasia. Author(s): Thomas D. Source: The Practitioner. 1997 July; 241(1576): 408-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9425714

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Why pressure-flow studies should be optional and not mandatory studies for evaluating men with benign prostatic hyperplasia. Author(s): McConnell JD. Source: Urology. 1994 August; 44(2): 156-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7519379

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Will laser replace TURP for the treatment of benign prostatic hyperplasia? Author(s): Fitzpatrick JM. Source: Lancet. 2000 July 29; 356(9227): 357-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10972365

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Workgroup #3: Monitoring effects of treatment for cancer and for benign prostatic hyperplasia. Author(s): Jones GW, Smith RA, Batjer JD, Bostwick DG, Corn BW, Guess HA, Hudson MA, Kabalin J, Soloway MS. Source: Cancer. 1993 April 15; 71(8): 2681-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7680953

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Worldwide patterns of prevalence and mortality from benign prostatic hyperplasia. Author(s): Napalkov P, Maisonneuve P, Boyle P. Source: Urology. 1995 September; 46(3 Suppl A): 41-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7544516

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Zinc and magnesium serum levels in patients with benign prostatic hyperplasia (BPH) before and after prazosin therapy. Author(s): Dutkiewicz S. Source: Mater Med Pol. 1995 January-March; 27(1): 15-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8569270

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Zonal variation of apoptosis and proliferation in the normal prostate and in benign prostatic hyperplasia. Author(s): Colombel M, Vacherot F, Diez SG, Fontaine E, Buttyan R, Chopin D. Source: British Journal of Urology. 1998 September; 82(3): 380-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9772874

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Zone-dependent expression of estrogen receptors alpha and beta in human benign prostatic hyperplasia. Author(s): Tsurusaki T, Aoki D, Kanetake H, Inoue S, Muramatsu M, Hishikawa Y, Koji T. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 March; 88(3): 133340. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12629127

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Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and benign prostatic hyperplasia.

Finding Nutrition Studies on Benign Prostatic Hyperplasia The National Institutes of Health’s Office of Dietary Supplements (ODS) offers a searchable bibliographic database called the IBIDS (International Bibliographic Information on Dietary Supplements; National Institutes of Health, Building 31, Room 1B29, 31 Center Drive, MSC 2086, Bethesda, Maryland 20892-2086, Tel: 301-435-2920, Fax: 301-480-1845, E-mail: [email protected]). The IBIDS contains over 460,000 scientific citations and summaries about dietary supplements and nutrition as well as references to published international, scientific literature on dietary supplements such as vitamins, minerals, and botanicals.7 The IBIDS includes references and citations to both human and animal research studies. As a service of the ODS, access to the IBIDS database is available free of charge at the following Web address: http://ods.od.nih.gov/databases/ibids.html. After entering the search area, you have three choices: (1) IBIDS Consumer Database, (2) Full IBIDS Database, or (3) Peer Reviewed Citations Only. Now that you have selected a database, click on the “Advanced” tab. An advanced search allows you to retrieve up to 100 fully explained references in a comprehensive format. Type “benign prostatic hyperplasia” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.

7

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

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

Alternative medications for benign prostatic hyperplasia available on the Internet: a review of the evidence for their use. Author(s): Bristol Urological Institute, Southmead Hospital, UK. [email protected] Source: Meyer, J P Gillatt, D A BJU-Int. 2002 July; 90(1): 41-4 1464-4096

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Association of vitamin D receptor and 17 hydroxylase gene polymorphisms with benign prostatic hyperplasia and benign prostatic enlargement. Author(s): Department of Urology; Divisions of Applied and Experimental Oncology Institute of Cancer Research, University of Vienna, Vienna, Austria. Source: Schatzl, G Gsur, A Bernhofer, G Haidinger, G Hinteregger, S Vutuc, C Haitel, A Micksche, M Marberger, M Madersbacher, S Urology. 2001 Mar; 57(3): 567-72 1527-9995

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Beneficial effect of intranasal desmopressin for men with benign prostatic hyperplasia and nocturia: preliminary results. Author(s): Division of Urologic Surgery, University of Pittsburgh, School of Medicine, Pennsylvania, USA. Source: Chancellor, M B Atan, A Rivas, D A Watanabe, T Tai, H L Kumon, H Tech-Urol. 1999 December; 5(4): 191-4 1079-3259

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Cytopathological changes in early stages of benign prostatic hyperplasia upon exposure to sustained delivery of androgens. Author(s): University of Mississippi Medical Center, School of Health Related Professions, Jackson, MS 39216, USA. Source: Pollan, M C Benghuzzi, H A Tucci, M Biomed-Sci-Instrum. 2002; 38: 15-20 00678856

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Endocrine therapy for benign prostatic hyperplasia in the 90's. Author(s): Department of Urology, Karolinska Hospital, Stockholm, Sweden. Source: Ekman, P J-Urol-(Paris). 1995; 101(1): 22-5 0248-0018

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Extracts from fruits of saw palmetto (Sabal serrulata) and roots of stinging nettle (Urtica dioica): viable alternatives in the medical treatment of benign prostatic hyperplasia and associated lower urinary tracts symptoms. Source: Koch, E. Planta-med. Stuttgart : Georg Thieme Verlag,. August 2001. volume 67 (6) page 489-500. 0032-0943

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Interstitial laser therapy for benign prostatic hyperplasia in the anticoagulated patient. Author(s): Division of Urology, University of California, San Diego, and Veterans Affairs Medical Center, San Diego, California, 92103-8897, USA. Source: Polepalle, S Monga, M Tech-Urol. 2001 December; 7(4): 285-7 1079-3259

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Management of urinary retention due to benign prostatic hyperplasia using luteinizing hormone-releasing hormone agonist. Author(s): James Buchanan Brady Urological Institute, Johns Hopkins Medical Institutions, Baltimore, Maryland. Source: Schlegel, P N Brendler, C B Urology. 1989 August; 34(2): 69-72 0090-4295

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Morphometry of benign prostatic hyperplasia during androgen suppressive therapy. Relationships among epithelial content, PSA density, and clinical outcome. Author(s): Department of Pathology, Aker Hospital, Oslo, Norway. Source: Svindland, A Eri, L M Tveter, K J Scand-J-Urol-Nephrol-Suppl. 1996; 179113-7 0300-8886

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Randomized trial of a combination of natural products (cernitin, saw palmetto, Bsitosterol, vitamin E) on symptoms of benign prostatic hyperplasia (BPH). Author(s): Department of Physiology and Biophysics, Georgetown University Medical Center, Washington, DC 20007, USA. [email protected] Source: Preuss, H G Marcusen, C Regan, J Klimberg, I W Welebir, T A Jones, W A IntUrol-Nephrol. 2001; 33(2): 217-25 0301-1623

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Serum prostate-antigen levels in patients with benign prostatic hypertrophy treated with leuprolide. Author(s): Department of Medicine, Mount Sinai School of Medicine, New York, New York. Source: Levine, A C Kirschenbaum, A Kaplan, P Droller, M A Gabrilove, J L Urology. 1989 July; 34(1): 10-3 0090-4295

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Serum-free coculture of stromal and epithelial cells from benign prostatic hyperplasia with keratinocyte growth factor. Author(s): Department of Urology, Yokohama City University School of Medicine, Yokohama, Japan. Source: Hashiba, T Noguchi, S Tsuchiya, F Takeda, M Masuda, M Kubota, Y Hosaka, M Urol-Int. 2000; 64(4): 209-12 0042-1138

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Significance of vitamin D receptor gene polymorphism for risk and disease severity of prostate cancer and benign prostatic hyperplasia in Japanese. Author(s): Department of of Urology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Fukuoka, Japan. [email protected] Source: Hamasaki, T Inatomi, H Katoh, T Ikuyama, T Matsumoto, T Urol-Int. 2002; 68(4): 226-31 0042-1138

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Treatment of symptomatic benign prostatic hyperplasia with beta-sitosterol: an 18month follow-up. Author(s): Department of Urology, Ruhr-University of Bochum, Herne, Germany. Source: Berges, R R Kassen, A Senge, T BJU-Int. 2000 May; 85(7): 842-6 1464-4096

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

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

Minerals Copper Source: Healthnotes, Inc.; www.healthnotes.com Stinging Nettle Alternative names: Urtica dioica, Urtica urens, Nettle Source: Integrative Medicine Communications; www.drkoop.com Zinc Source: Healthnotes, Inc.; www.healthnotes.com Zinc Source: Prima Communications, Inc.www.personalhealthzone.com Zinc Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10071,00.html

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Food and Diet Polyunsaturated Fats Source: Healthnotes, Inc.; www.healthnotes.com Pumpkin Seeds Source: Healthnotes, Inc.; www.healthnotes.com

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CHAPTER 3. ALTERNATIVE MEDICINE AND BENIGN PROSTATIC HYPERPLASIA Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to benign prostatic hyperplasia. 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 benign prostatic hyperplasia 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 “benign prostatic hyperplasia” (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 benign prostatic hyperplasia: •

(TURF) transurethral radiofrequency heating for benign prostatic hyperplasia at various temperatures with Thermex II: clinical experience. Author(s): Vandenbossche M, Peltier A, Schulman CC. Source: European Urology. 1993; 23(2): 302-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7683991

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A double-blind trial of an extract of the plant Serenoa repens in benign prostatic hyperplasia. Author(s): Champault G, Patel JC, Bonnard AM. Source: British Journal of Clinical Pharmacology. 1984 September; 18(3): 461-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6207850

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A double-blind trial of the effect of beta-sitosteryl glucoside (WA184) in the treatment of benign prostatic hyperplasia. Author(s): Kadow C, Abrams PH. Source: European Urology. 1986; 12(3): 187-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2423337

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A multicentric, placebo-controlled, double-blind clinical trial of beta-sitosterol (phytosterol) for the treatment of benign prostatic hyperplasia. German BPH-Phyto Study group. Author(s): Klippel KF, Hiltl DM, Schipp B. Source: British Journal of Urology. 1997 September; 80(3): 427-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9313662

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A study of prostane in the treatment of benign prostatic hyperplasia. Author(s): Upadhyay L, Tripathi K, Kulkarni KS. Source: Phytotherapy Research : Ptr. 2001 August; 15(5): 411-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11507733

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A systematic review of Cernilton for the treatment of benign prostatic hyperplasia. Author(s): MacDonald R, Ishani A, Rutks I, Wilt TJ. Source: Bju International. 2000 May; 85(7): 836-41. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10792162

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Alternative medications for benign prostatic hyperplasia available on the Internet: a review of the evidence for their use. Author(s): Meyer JP, Gillatt DA. Source: Bju International. 2002 July; 90(1): 41-4. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12081767

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Benign prostatic hyperplasia treated with saw palmetto: a literature search and an experimental case study. Author(s): McPartland JM, Pruitt PL. Source: J Am Osteopath Assoc. 2000 February; 100(2): 89-96. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10732392

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Benign prostatic hyperplasia, sexual function, and overall evaluation of the male patient. Author(s): Hellstrom WJ. Source: J Am Osteopath Assoc. 2004 February; 104(2 Suppl 2): S5-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15038397

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Benign prostatic hyperplasia. Author(s): Barry M, Roehrborn C.

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Source: Clin Evid. 2002 June; (7): 775-87. Review. No Abstract Available. Update In: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12230703 •

Benign prostatic hyperplasia. Author(s): Barry MJ, Roehrborn CG. Source: Bmj (Clinical Research Ed.). 2001 November 3; 323(7320): 1042-6. Review. Erratum In: Bmj 2002 March 30; 324(7340): 775. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11691764

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Benign prostatic hyperplasia. Patient evaluation and relief of obstructive symptoms. Author(s): Chow RD. Source: Geriatrics. 2001 March; 56(3): 33-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11252759

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Benign prostatic hyperplasia: challenges for the new millennium. Author(s): Cabelin MA, Te AE, Kaplan SA. Source: Current Opinion in Urology. 2000 July; 10(4): 301-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10918967

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Benign prostatic hyperplasia: solutions to an ageing problem. Author(s): Foley CL, Bott SR, Arya M, Kirby RS. Source: Hosp Med. 2002 August; 63(8): 460-4. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12212416

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Benign prostatic hyperplasia: US-guided transrectal urethral enlargement with radio frequency--initial results in a canine model. Author(s): Goldberg SN, Hahn PF, McGovern FJ, Fogle RM, Mueller PR, Gazelle GS. Source: Radiology. 1998 August; 208(2): 491-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9680581

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beta-sitosterol for the treatment of benign prostatic hyperplasia: a systematic review. Author(s): Wilt TJ, MacDonald R, Ishani A. Source: Bju International. 1999 June; 83(9): 976-83. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10368239

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Beta-sitosterols for benign prostatic hyperplasia. Author(s): Cochrane Database Syst Rev. 2002;(3):CD001423 Source: Cochrane Database Syst Rev. 2000; (2): Cd001043. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12137626

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Cell-kill modeling of microwave thermotherapy for treatment of benign prostatic hyperplasia. Author(s): Bolmsjo M, Schelin S, Wagrell L, Larson T, de la Rosette JJ, Mattiasson A. Source: Journal of Endourology / Endourological Society. 2000 October; 14(8): 627-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11083404

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Cernilton for benign prostatic hyperplasia. Author(s): Wilt T, Mac Donald R, Ishani A, Rutks I, Stark G. Source: Cochrane Database Syst Rev. 2000; (2): Cd001042. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10796739

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Changes in the prevalence of benign prostatic hyperplasia in China. Author(s): Gu F. Source: Chinese Medical Journal. 1997 March; 110(3): 163-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9594331

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Changing approaches in the treatment of benign prostatic hyperplasia. Author(s): Schroder FH. Source: European Urology. 1991; 20 Suppl 1: 63-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1722165

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Clinical and retrospective evaluation of Eviprostat: a non-hormonal and nonneuropharmacological agent for benign prostatic hyperplasia. Author(s): Ishigooka M, Hashimoto T, Hayami S, Tomaru M, Nakada T, Mitobe K. Source: International Urology and Nephrology. 1995; 27(1): 61-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7542229

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Clinical evaluation of long-term treatment using cernitin pollen extract in patients with benign prostatic hyperplasia. Author(s): Yasumoto R, Kawanishi H, Tsujino T, Tsujita M, Nishisaka N, Horii A, Kishimoto T. Source: Clinical Therapeutics. 1995 January-February; 17(1): 82-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7538904

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Clinical relevance of growth factor antagonists in the treatment of benign prostatic hyperplasia. Author(s): Desgrandchamps F. Source: European Urology. 1997; 32 Suppl 1: 28-31. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9218940

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Combined extracts of Urtica dioica and Pygeum africanum in the treatment of benign prostatic hyperplasia: double-blind comparison of two doses. Author(s): Krzeski T, Kazon M, Borkowski A, Witeska A, Kuczera J.

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Source: Clinical Therapeutics. 1993 November-December; 15(6): 1011-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7509261 •

Combined sabal and urtica extract compared with finasteride in men with benign prostatic hyperplasia: analysis of prostate volume and therapeutic outcome. Author(s): Sokeland J. Source: Bju International. 2000 September; 86(4): 439-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10971268

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Comparative effects of alfuzosin versus Serenoa repens in the treatment of symptomatic benign prostatic hyperplasia. Author(s): Grasso M, Montesano A, Buonaguidi A, Castelli M, Lania C, Rigatti P, Rocco F, Cesana BM, Borghi C. Source: Arch Esp Urol. 1995 January-February; 48(1): 97-103. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7537488

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Comparative study of concentration of isoflavones and lignans in plasma and prostatic tissues of normal control and benign prostatic hyperplasia. Author(s): Hong SJ, Kim SI, Kwon SM, Lee JR, Chung BC. Source: Yonsei Medical Journal. 2002 April; 43(2): 236-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11971218

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Comparison of a phytotherapeutic agent (Permixon) with an alpha-blocker (Tamsulosin) in the treatment of benign prostatic hyperplasia: a 1-year randomized international study. Author(s): Debruyne F, Koch G, Boyle P, Da Silva FC, Gillenwater JG, Hamdy FC, Perrin P, Teillac P, Vela-Navarrete R, Raynaud JP. Source: European Urology. 2002 May; 41(5): 497-506; Discussion 506-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12074791

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Comparison of fatty acid profiles in the serum of patients with prostate cancer and benign prostatic hyperplasia. Author(s): Yang YJ, Lee SH, Hong SJ, Chung BC. Source: Clinical Biochemistry. 1999 August; 32(6): 405-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10667474

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Comparison of once and twice daily dosage forms of Pygeum africanum extract in patients with benign prostatic hyperplasia: a randomized, double-blind study, with long-term open label extension. Author(s): Chatelain C, Autet W, Brackman F. Source: Urology. 1999 September; 54(3): 473-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10475357

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Conservative non-instrumental treatment of benign prostatic hyperplasia. Author(s): Ruud Bosch JL. Source: Urological Research. 1997; 25 Suppl 2: S107-14. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9144895

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Current concepts in the pharmacotherapy of benign prostatic hyperplasia. Author(s): Khastgir J, Arya M, Shergill IS, Kalsi JS, Minhas S, Mundy AR. Source: Expert Opinion on Pharmacotherapy. 2002 December; 3(12): 1727-37. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12472370

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Detection of telomerase activity in prostate massage samples improves differentiating prostate cancer from benign prostatic hyperplasia. Author(s): Vicentini C, Gravina GL, Angelucci A, Pascale E, D'Ambrosio E, Muzi P, Leonardo GD, Fileni A, Tubaro A, Festuccia C, Bologna M. Source: Journal of Cancer Research and Clinical Oncology. 2004 April; 130(4): 217-21. Epub 2004 January 29. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14749923

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Effects of a saw palmetto herbal blend in men with symptomatic benign prostatic hyperplasia. Author(s): Marks LS, Partin AW, Epstein JI, Tyler VE, Simon I, Macairan ML, Chan TL, Dorey FJ, Garris JB, Veltri RW, Santos PB, Stonebrook KA, deKernion JB. Source: The Journal of Urology. 2000 May; 163(5): 1451-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10751856

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Effects of Bowman-Birk inhibitor concentrate (BBIC) in patients with benign prostatic hyperplasia. Author(s): Malkowicz SB, McKenna WG, Vaughn DJ, Wan XS, Propert KJ, Rockwell K, Marks SH, Wein AJ, Kennedy AR. Source: The Prostate. 2001 June 15; 48(1): 16-28. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11391683

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Effects of long-term treatment with Serenoa repens (Permixon) on the concentrations and regional distribution of androgens and epidermal growth factor in benign prostatic hyperplasia. Author(s): Di Silverio F, Monti S, Sciarra A, Varasano PA, Martini C, Lanzara S, D'Eramo G, Di Nicola S, Toscano V. Source: The Prostate. 1998 October 1; 37(2): 77-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9759701

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Effects of stinging nettle root extracts and their steroidal components on the Na+,K(+)-ATPase of the benign prostatic hyperplasia. Author(s): Hirano T, Homma M, Oka K.

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Source: Planta Medica. 1994 February; 60(1): 30-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7510891 •

Effects of the sabal serrulata extract IDS 89 and its subfractions on 5 alpha-reductase activity in human benign prostatic hyperplasia. Author(s): Weisser H, Tunn S, Behnke B, Krieg M. Source: The Prostate. 1996 May; 28(5): 300-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8610056

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Efficacy and acceptability of tadenan (Pygeum africanum extract) in the treatment of benign prostatic hyperplasia (BPH): a multicentre trial in central Europe. Author(s): Breza J, Dzurny O, Borowka A, Hanus T, Petrik R, Blane G, Chadha-Boreham H. Source: Current Medical Research and Opinion. 1998; 14(3): 127-39. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9787978

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Efficacy and tolerability of drugs for treatment of benign prostatic hyperplasia. Author(s): Dutkiewics S. Source: International Urology and Nephrology. 2001; 32(3): 423-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11583366

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Efficacy and tolerability of the lipidosterolic extract of Serenoa repens (Permixon) in benign prostatic hyperplasia: a double-blind comparison of two dosage regimens. Author(s): Stepanov VN, Siniakova LA, Sarrazin B, Raynaud JP. Source: Adv Ther. 1999 September-October; 16(5): 231-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10915398

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Enzyme activities in tissue of human benign prostatic hyperplasia after three months' treatment with the Sabal serrulata extract IDS 89 (Strogen) or placebo. Author(s): Weisser H, Behnke B, Helpap B, Bach D, Krieg M. Source: European Urology. 1997; 31(1): 97-101. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9032543

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Extracts from fruits of saw palmetto (Sabal serrulata) and roots of stinging nettle (Urtica dioica): viable alternatives in the medical treatment of benign prostatic hyperplasia and associated lower urinary tracts symptoms. Author(s): Koch E. Source: Planta Medica. 2001 August; 67(6): 489-500. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11509966

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Future concepts in the medical therapy of benign prostatic hyperplasia. Author(s): Cuellar DC, Kyprianou N.

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Source: Current Opinion in Urology. 2001 January; 11(1): 27-33. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11148743 •

Future drugs for the treatment of benign prostatic hyperplasia. Author(s): Andersson KE, Chapple CR, Hofner K. Source: World Journal of Urology. 2002 April; 19(6): 436-42. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12022712

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Herbal medications in the treatment of benign prostatic hyperplasia (BPH). Author(s): Am Fam Physician. 2002 Jul 1;66(1):87-8 Source: The Urologic Clinics of North America. 2002 February; 29(1): 23-9, Vii. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12126035

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Herbs for benign prostatic hyperplasia. Author(s): Dvorkin L, Song KY. Source: The Annals of Pharmacotherapy. 2002 September; 36(9): 1443-52. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12196065

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Hyperthermia and thermotherapy of benign prostatic hyperplasia: a critical review. Author(s): Schulman CC, Vanden Bossche M. Source: European Urology. 1993; 23 Suppl 1: 53-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7685698

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Is screening for prostate cancer necessary in men with symptoms of benign prostatic hyperplasia? Author(s): Hall MC, Roehrborn CG, McConnell JD. Source: Semin Urol Oncol. 1996 August; 14(3): 122-33. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8865473

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Local microwave hyperthermia of benign prostatic hyperplasia. Author(s): Strohmaier WL, Bichler KH, Fluchter SH, Wilbert DM. Source: The Journal of Urology. 1990 October; 144(4): 913-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1697915

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Long-term clinical and biologic effects of the lipidosterolic extract of Serenoa repens in patients with symptomatic benign prostatic hyperplasia. Author(s): Pytel YA, Vinarov A, Lopatkin N, Sivkov A, Gorilovsky L, Raynaud JP. Source: Adv Ther. 2002 November-December; 19(6): 297-306. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12665050

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Lower urinary tract symptoms/benign prostatic hyperplasia: fast control of the patient's quality of life. Author(s): Djavan B. Source: Urology. 2003 September; 62(3 Suppl 1): 6-14. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12957195

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Lower urinary tract symptoms/benign prostatic hyperplasia: minimizing morbidity caused by treatment. Author(s): Schulman CC. Source: Urology. 2003 September; 62(3 Suppl 1): 24-33. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12957197

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Managing benign prostatic hyperplasia. Author(s): Dull P, Reagan RW Jr, Bahnson RR. Source: American Family Physician. 2002 July 1; 66(1): 77-84. Review. Summary for Patients In: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12126034

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Medical management of benign prostatic hyperplasia other than with hormones or alpha blockers. Author(s): Fitzpatrick JM, Dreikorn K, Habib F, Mebust WK, Perrin P, Schulze HK. Source: Prog Clin Biol Res. 1994; 386: 303-9. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7528399

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Medical management of benign prostatic hyperplasia. Author(s): Chacon A, Monga M. Source: Geriatric Nephrology and Urology. 1999; 9(1): 39-48. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10435226

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Medical management of benign prostatic hyperplasia: a review. Author(s): Magoha GA. Source: East Afr Med J. 1996 July; 73(7): 453-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8918007

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Meta-analysis of clinical trials of permixon in the treatment of symptomatic benign prostatic hyperplasia. Author(s): Boyle P, Robertson C, Lowe F, Roehrborn C. Source: Urology. 2000 April; 55(4): 533-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10736497

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Minimally invasive therapies for benign prostatic hyperplasia. Author(s): Blute ML, Larson T.

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Source: Urology. 2001 December; 58(6 Suppl 1): 33-40; Discussion 40-1. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11750248 •

Minimally invasive therapies for the treatment of symptomatic benign prostatic hyperplasia: the University of Florida experience. Author(s): Narayan P, Starling J. Source: Journal of Clinical Laser Medicine & Surgery. 1998 February; 16(1): 29-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9728127

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New innovative therapies for benign prostatic hyperplasia: any advance? Author(s): Klingler HC. Source: Current Opinion in Urology. 2003 January; 13(1): 11-5. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12490810

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Newly developed transurethral radiofrequency thermotherapy device for benign prostatic hyperplasia: a pilot study in canine prostate. Author(s): Terai A, Arai Y, Yamamoto I, Onishi H, Oishi K, Yoshida O. Source: International Journal of Hyperthermia : the Official Journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group. 1995 SeptemberOctober; 11(5): 627-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7594814

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Nonoperative management of benign prostatic hyperplasia. Author(s): Lepor H. Source: The Journal of Urology. 1989 June; 141(6): 1283-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2470925

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Pharmacotherapy for benign prostatic hyperplasia. Author(s): Narayan P, Indudhara R. Source: The Western Journal of Medicine. 1994 November; 161(5): 495-506. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7528957

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Pharmacotherapy for benign prostatic hyperplasia--the potential for alpha 1adrenoceptor subtype-specific blockade. Author(s): Chapple CR. Source: British Journal of Urology. 1998 March; 81 Suppl 1: 34-47; Discussion 64-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9589016

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Phytotherapeutic agents in the management of symptomatic benign prostatic hyperplasia. Author(s): Fitzpatrick JM, Lynch TH.

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Source: The Urologic Clinics of North America. 1995 May; 22(2): 407-12. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7539185 •

Phytotherapeutic agents in the treatment of benign prostatic hyperplasia. Author(s): Dreikorn K. Source: Curr Urol Rep. 2000 August; 1(2): 103-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12084323

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Phytotherapy for benign prostatic hyperplasia. Author(s): Gerber GS. Source: Curr Urol Rep. 2002 August; 3(4): 285-91. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12149159

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Phytotherapy for benign prostatic hyperplasia. Author(s): Wilt TJ, Ishani A, Rutks I, MacDonald R. Source: Public Health Nutrition. 2000 December; 3(4A): 459-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11276294

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Phytotherapy for treatment of benign prostatic hyperplasia: case not proven. Author(s): Fitzpatrick JM. Source: Urology. 1999 March; 53(3): 462-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10096367

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Phytotherapy in the management of benign prostatic hyperplasia. Author(s): Lowe FC. Source: Urology. 2001 December; 58(6 Suppl 1): 71-6; Discussion 76-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11750257

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Phytotherapy in the treatment of benign prostatic hyperplasia. Author(s): Lowe FC, Fagelman E. Source: Current Opinion in Urology. 2002 January; 12(1): 15-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11753128

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Phytotherapy in the treatment of benign prostatic hyperplasia: an update. Author(s): Lowe FC, Fagelman E. Source: Urology. 1999 April; 53(4): 671-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10197839

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Phytotherapy in treatment of benign prostatic hyperplasia: a critical review. Author(s): Lowe FC, Ku JC.

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Source: Urology. 1996 July; 48(1): 12-20. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8693632 •

Plant extracts in the medical management of benign prostatic hyperplasia: fact or fiction? Author(s): Mahoney JE. Source: Can J Urol. 1995 May; 2(2): 125-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12803719

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Pros-Eight transurethral radiofrequency thermotherapy for benign prostatic hyperplasia: preliminary clinical results. Author(s): Yoshida O, Terai A, Shichiri Y, Okada Y, Ishitoya S, Okubo K, Suzuki Y, Arai Y. Source: International Journal of Urology : Official Journal of the Japanese Urological Association. 1996 November; 3(6): 454-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9170572

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Pygeum africanum for benign prostatic hyperplasia. Author(s): Wilt T, Ishani A, Mac Donald R, Rutks I, Stark G. Source: Cochrane Database Syst Rev. 2002; (1): Cd001044. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11869585

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Pygeum africanum for the treatment of patients with benign prostatic hyperplasia: a systematic review and quantitative meta-analysis. Author(s): Ishani A, MacDonald R, Nelson D, Rutks I, Wilt TJ. Source: The American Journal of Medicine. 2000 December 1; 109(8): 654-64. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11099686

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Radiofrequency heat-treatment to the prostate for bladder outlet obstruction associated with benign prostatic hyperplasia: a 4-year outcome study. Author(s): Dawkins GP, Harrison NW, Ansell W. Source: British Journal of Urology. 1997 June; 79(6): 910-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9202558

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Randomised, placebo-controlled, double-blind clinical trial of beta-sitosterol in patients with benign prostatic hyperplasia. Beta-sitosterol Study Group. Author(s): Berges RR, Windeler J, Trampisch HJ, Senge T. Source: Lancet. 1995 June 17; 345(8964): 1529-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7540705

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Randomized trial of a combination of natural products (cernitin, saw palmetto, Bsitosterol, vitamin E) on symptoms of benign prostatic hyperplasia (BPH). Author(s): Preuss HG, Marcusen C, Regan J, Klimberg IW, Welebir TA, Jones WA.

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Source: International Urology and Nephrology. 2001; 33(2): 217-25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12092634 •

Reproducibility and clinical and concurrent validity of the MSF-4: a four-item male sexual function questionnaire for patients with benign prostatic hyperplasia. Author(s): Marquis P, Marrel A. Source: Value in Health : the Journal of the International Society for Pharmacoeconomics and Outcomes Research. 2001 July-August; 4(4): 335-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11705301

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Results of deep prostatic hyperthermia applied with Thermex II in 525 benign prostatic hyperplasias. Author(s): Yazicioglu AH, Dalva I, Ozgur S, Cetin S. Source: European Urology. 1993; 23(2): 322-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7683995

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Review: Pygeum africanum extracts improve symptoms and urodynamics in symptomatic benign prostatic hyperplasia. Author(s): Barry M. Source: Acp Journal Club. 2002 September-October; 137(2): 61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12207439

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Role of estrogens in human benign prostatic hyperplasia. Author(s): Sciarra F, Toscano V. Source: Archives of Andrology. 2000 May-June; 44(3): 213-20. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10864369

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Sabal serrulata extract (Strogen forte) in the treatment of symptomatic benign prostatic hyperplasia. Author(s): Kondas J, Philipp V, Dioszeghy G. Source: International Urology and Nephrology. 1996; 28(6): 767-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9089044

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Saw palmetto extract: newest (and oldest) treatment alternative for men with symptomatic benign prostatic hyperplasia. Author(s): Marks LS, Tyler VE. Source: Urology. 1999 March; 53(3): 457-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10096366

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Saw palmetto extracts for benign prostatic hyperplasia. Author(s): Segars LW.

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Source: The Journal of Family Practice. 1999 February; 48(2): 88-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10037530 •

Saw palmetto extracts for treatment of benign prostatic hyperplasia: a systematic review. Author(s): Wilt TJ, Ishani A, Stark G, MacDonald R, Lau J, Mulrow C. Source: Jama : the Journal of the American Medical Association. 1998 November 11; 280(18): 1604-9. Erratum In: Jama 1999 February 10; 281(6): 515. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9820264

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Saw palmetto for benign prostatic hyperplasia. Author(s): McKinney DE. Source: Jama : the Journal of the American Medical Association. 1999 May 12; 281(18): 1699. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10328068

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Serenoa repens (Permixon). A review of its pharmacology and therapeutic efficacy in benign prostatic hyperplasia. Author(s): Plosker GL, Brogden RN. Source: Drugs & Aging. 1996 November; 9(5): 379-95. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8922564

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Serenoa repens for benign prostatic hyperplasia. Author(s): Wilt T, Ishani A, Mac Donald R. Source: Cochrane Database Syst Rev. 2002; (3): Cd001423. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12137626

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Serenoa repens for benign prostatic hyperplasia. Author(s): Wilt T, Ishani A, Stark G, MacDonald R, Mulrow C, Lau J. Source: Cochrane Database Syst Rev. 2000; (2): Cd001423. Review. Update In: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10796790

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The assessment of medical treatment for benign prostatic hyperplasia (BPH). Author(s): Roehrborn CG. Source: Prog Clin Biol Res. 1994; 386: 175-90. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7528385

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The effect of phytosterols on quality of life in the treatment of benign prostatic hyperplasia. Author(s): Coleman CI, Hebert JH, Reddy P.

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Source: Pharmacotherapy. 2002 November; 22(11): 1426-32. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12432969 •

The lipidosterolic extract of Serenoa repens in the treatment of benign prostatic hyperplasia: a comparison of two dosage regimens. Author(s): Giannakopoulos X, Baltogiannis D, Giannakis D, Tasos A, Sofikitis N, Charalabopoulos K, Evangelou A. Source: Adv Ther. 2002 November-December; 19(6): 285-96. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12665049

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The medical management of lower urinary tract symptoms and benign prostatic hyperplasia. Author(s): Holtgrewe HL. Source: The Urologic Clinics of North America. 1998 November; 25(4): 555-69, Vii. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10026765

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The role of phytotherapy in treating lower urinary tract symptoms and benign prostatic hyperplasia. Author(s): Dreikorn K. Source: World Journal of Urology. 2002 April; 19(6): 426-35. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12022711

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Tissue ablation in benign prostatic hyperplasia with high-intensity focused ultrasound. Author(s): Madersbacher S, Kratzik C, Szabo N, Susani M, Vingers L, Marberger M. Source: European Urology. 1993; 23 Suppl 1: 39-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7685695

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Transrectal hyperthermia-induced histological and ultrastructural changes of human benign prostatic hyperplasia tissue. Author(s): Montorsi F, Guazzoni G, Colombo R, Bulfamante G, Galli L, Matozzo V, Consonni P, Rigatti P. Source: European Urology. 1992; 22(1): 74-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1385146

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Transurethral microwave thermotherapy (TUMT) for benign prostatic hyperplasia (BPH)--our first 100 cases. Author(s): Lee KT, Tan HH, Li MK, Cheng WS, Rekhraj IR, Foo KT. Source: Singapore Med J. 1995 April; 36(2): 181-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7545827

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Transurethral thermotherapy in the management of benign prostatic hyperplasia. Author(s): Sofras F, Sakkas G, Kontothanassis D, Lyssiotis F, Tamvakis N. Source: International Urology and Nephrology. 1996; 28(5): 673-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9061427

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Treatment of benign prostatic hyperplasia with phytosterols. Author(s): Carbin BE, Larsson B, Lindahl O. Source: British Journal of Urology. 1990 December; 66(6): 639-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1702340

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Treatment of symptomatic benign prostatic hyperplasia with beta-sitosterol: an 18month follow-up. Author(s): Berges RR, Kassen A, Senge T. Source: Bju International. 2000 May; 85(7): 842-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10792163

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Treatment response with transurethral radiofrequency thermotherapy for symptomatic benign prostatic hyperplasia. Author(s): Hong SJ, Choi HR, Lee T, Kang YS. Source: Yonsei Medical Journal. 1994 September; 35(3): 279-85. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7526562

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Treatment strategies, patterns of drug use and treatment discontinuation in men with LUTS suggestive of benign prostatic hyperplasia: the Triumph project. Author(s): Verhamme KM, Dieleman JP, Bleumink GS, Bosch JL, Stricker BH, Sturkenboom MC. Source: European Urology. 2003 November; 44(5): 539-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14572751

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Trends in prostatectomy for benign prostatic hyperplasia among black and white men in the United States: 1980 to 1994. Author(s): Xia Z, Roberts RO, Schottenfeld D, Lieber MM, Jacobsen SJ. Source: Urology. 1999 June; 53(6): 1154-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10367845

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Updated meta-analysis of clinical trials of Serenoa repens extract in the treatment of symptomatic benign prostatic hyperplasia. Author(s): Boyle P, Robertson C, Lowe F, Roehrborn C. Source: Bju International. 2004 April; 93(6): 751-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15049985

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Usefulness of Cernilton in the treatment of benign prostatic hyperplasia. Author(s): Dutkiewicz S.

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Source: International Urology and Nephrology. 1996; 28(1): 49-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8738619

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

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

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

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

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

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

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

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

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

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

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

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

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

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

The following is a specific Web list relating to benign prostatic hyperplasia; 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 Benign Prostatic Hyperplasia Source: Healthnotes, Inc.; www.healthnotes.com Benign Prostatic Hyperplasia Source: Integrative Medicine Communications; www.drkoop.com Benign Prostatic Hyperplasia Alternative names: Prostate Enlargement Source: Prima Communications, Inc.www.personalhealthzone.com BPH Source: Integrative Medicine Communications; www.drkoop.com

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Obesity Source: Integrative Medicine Communications; www.drkoop.com Prostate Cancer Source: Integrative Medicine Communications; www.drkoop.com Prostate Enlargement Source: Integrative Medicine Communications; www.drkoop.com Prostate Infection Source: Integrative Medicine Communications; www.drkoop.com Prostatitis Source: Healthnotes, Inc.; www.healthnotes.com Prostatitis Source: Integrative Medicine Communications; www.drkoop.com Urinary Incontinence Source: Integrative Medicine Communications; www.drkoop.com •

Homeopathy Apis Mellifica Source: Healthnotes, Inc.; www.healthnotes.com Causticum Source: Healthnotes, Inc.; www.healthnotes.com Chimaphila Umbellata Source: Healthnotes, Inc.; www.healthnotes.com Clematis Source: Healthnotes, Inc.; www.healthnotes.com Lycopodium Source: Healthnotes, Inc.; www.healthnotes.com Pulsatilla Source: Healthnotes, Inc.; www.healthnotes.com Sabal Serrulata Source: Healthnotes, Inc.; www.healthnotes.com Staphysagria Source: Healthnotes, Inc.; www.healthnotes.com Thuja Occidentalis Source: Healthnotes, Inc.; www.healthnotes.com

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•

Herbs and Supplements Alanine Source: Healthnotes, Inc.; www.healthnotes.com Amino Acids Overview Source: Healthnotes, Inc.; www.healthnotes.com Androstenedione Source: Healthnotes, Inc.; www.healthnotes.com Athletic Performance Source: Healthnotes, Inc.; www.healthnotes.com Beta-Sitosterol Source: Healthnotes, Inc.; www.healthnotes.com Beta-Sitosterol Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,972,00.html Butcher's Broom Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10010,00.html Collinsonia Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Doxazosin Source: Healthnotes, Inc.; www.healthnotes.com Ephedra Alternative names: Ephedra sinica, Ephedra intermedia, Ephedra equisetina Source: Healthnotes, Inc.; www.healthnotes.com Ephedra (Ma huang) Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,777,00.html Finasteride Source: Healthnotes, Inc.; www.healthnotes.com GLA (Gamma-Linolenic Acid) Source: Prima Communications, Inc.www.personalhealthzone.com Glutamic Acid Source: Healthnotes, Inc.; www.healthnotes.com

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Glycine Source: Healthnotes, Inc.; www.healthnotes.com Lycopene Source: Healthnotes, Inc.; www.healthnotes.com Nettle Alternative names: Urtica dioica Source: Healthnotes, Inc.; www.healthnotes.com Nettle Source: Integrative Medicine Communications; www.drkoop.com Nettle Source: Prima Communications, Inc.www.personalhealthzone.com Nettle Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10048,00.html Pollen Source: Healthnotes, Inc.; www.healthnotes.com Pumpkin Alternative names: Cucurbita pepo, Cucurbita maxima Source: Healthnotes, Inc.; www.healthnotes.com Pygeum Alternative names: African Prune; Pygeum africanum Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Pygeum Alternative names: Prunus africanum, Pygeum africanum Source: Healthnotes, Inc.; www.healthnotes.com Pygeum Source: Prima Communications, Inc.www.personalhealthzone.com Pygeum Africanum Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10052,00.html Sabal Serrulata Source: Integrative Medicine Communications; www.drkoop.com Saw Palmetto Alternative names: Serenoa serrulata, Serenoa repens, Sabal serrulata Source: Healthnotes, Inc.; www.healthnotes.com

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Saw Palmetto Alternative names: Serenoa repens, Sabal serrulata Source: Integrative Medicine Communications; www.drkoop.com Saw Palmetto Source: Prima Communications, Inc.www.personalhealthzone.com Saw Palmetto Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Saw Palmetto Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,819,00.html Serenoa Repens Source: Integrative Medicine Communications; www.drkoop.com Sitosterol Source: Prima Communications, Inc.www.personalhealthzone.com Tamsulosin Source: Healthnotes, Inc.; www.healthnotes.com Terazosin Source: Healthnotes, Inc.; www.healthnotes.com Urtica Dioica Source: Integrative Medicine Communications; www.drkoop.com Urtica Urens Source: Integrative Medicine Communications; www.drkoop.com

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

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CHAPTER 4. HYPERPLASIA

PATENTS

ON

BENIGN

PROSTATIC

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

Patents on Benign Prostatic Hyperplasia By performing a patent search focusing on benign prostatic hyperplasia, 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 8Adapted

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

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descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We will tell you how to obtain this information later in the chapter. The following is an example of the type of information that you can expect to obtain from a patent search on benign prostatic hyperplasia: •

Alpha 1a adrenergic receptor antagonists Inventor(s): Bock; Mark G. (Hatfield, PA), Lagu; Bharat (Maywood, NJ), Newton; Randall C. (West Point, PA), Patane; Michael A. (Harleysville, PA) Assignee(s): Merck & Co., Inc (Rahway, NJ), Synaptic Pharmaceutical Corporation (Paramus, NJ) Patent Number: 6,376,503 Date filed: June 17, 1998 Abstract: This invention relates to certain novel compounds and derivatives thereof, their synthesis, and their use as alpha 1a adrenergic receptor antagonists. One application of these compounds is in the treatment of benign prostatic hyperplasia. These compounds are selective in their ability to relax smooth muscle tissue enriched in the alpha 1a receptor subtype without at the same time inducing hypotension. One such tissue is found surrounding the urethral lining. Therefore, one utility of the instant compounds is to provide acute relief to males suffering from benign prostatic hyperplasia, by permitting less hindered urine flow. Another utility of the instant compounds is provided by combination with a human 5-alpha reductase inhibitory compound, such that both acute and chronic relief from the effects of benign prostatic hyperplasia are achieved. Excerpt(s): This invention relates to certain novel compounds and derivatives thereof, their synthesis, and their use as alpha 1a adrenoceptor antagonists. More particularly, the compounds of the present invention are useful for treating benign prostatic hyperplasia (BPH). Human adrenergic receptors are integral membrane proteins which have been classified into two broad classes, the alpha and the beta adrenergic receptors. Both types mediate the action of the peripheral sympathetic nervous system upon binding of catecholamines, norepinephrine and epinephrine. Norepinephrine is produced by adrenergic nerve endings, while epinephrine is produced by the adrenal medulla. The binding affinity of adrenergic receptors for these compounds forms one basis of the classification: alpha receptors bind norepinephrine more strongly than epinephrine and much more strongly than the synthetic compound isoproterenol. The binding affinity of these hormones is reversed for the beta receptors. In many tissues, the functional responses, such as smooth muscle contraction, induced by alpha receptor activation are opposed to responses induced by beta receptor binding. Web site: http://www.delphion.com/details?pn=US06376503__

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Arylhydantoin derivatives and uses thereof Inventor(s): Bock; Mark G. (Hatfield, PA), DiPardo; Robert M. (Lansdale, PA), Hoffman; Jacob M. (Lansdale, PA), Patane; Michael A. (Harleysville, PA), Payne; Linda S. (Lansdale, PA) Assignee(s): Merck & Co., Inc. (Rahway, NJ) Patent Number: 6,436,962 Date filed: September 27, 2000 Abstract: Arylhydantoin derivatives and their pharmaceutically acceptable salts are disclosed. The synthesis of these compounds and their use as alpha 1a adrenergic receptor antagonists is also described. One application of these compounds is in the treatment of benign prostatic hyperplasia. These compounds are typically selective in their ability to relax smooth muscle tissue enriched in the alpha 1a receptor subtype without at the same time inducing hypotension. One such tissue is found surrounding the urethral lining. Therefore, one utility of the instant compounds is to provide acute relief to males suffering from benign prostatic hyperplasia, by permitting less hindered urine flow. Another utility of the instant compounds is provided by combination with a human 5-alpha reductase inhibitory compound, such that both acute and chronic relief from the effects of benign prostatic hyperplasia can be achieved. Excerpt(s): The present invention relates to arylhydantoin derivatives and pharmaceutically acceptable salts thereof, their synthesis, and their use as alpha 1a adrenoceptor antagonists. The arylhydantoin derivatives of the present invention include, but are not limited to, compounds having (1-azacycloalkyl)alkyl, ((4-amino)-1azacycloalkyl)alkyl, or (spiroazacycloalkyl)alkyl groups as side chains on a hydantoin ring nitrogen. The compounds of the present invention are useful for treating benign prostatic hyperplasia (BPH). References are made throughout this application to various publications, the disclosures of which are hereby incorporated by reference in their entireties, in order to more fully describe the state of the art to which this invention pertains. Human adrenergic receptors are integral membrane proteins which have been classified into two broad classes, the alpha and the beta adrenergic receptors. Both types mediate the action of the peripheral sympathetic nervous system upon binding of catecholamines, norepinephrine and epinephrine. Web site: http://www.delphion.com/details?pn=US06436962__

•

Combination therapy for the prophylaxis and/or treatment of benign prostatic hyperplasia Inventor(s): Labrie; Fernand (Ste-Foy, CA) Assignee(s): Endorecherche, Inc. (CA) Patent Number: 6,423,698 Date filed: June 7, 1995 Abstract: A combination therapy for the prophylaxis and/or treatment of benign prostatic hyperplasia in susceptible warm-blooded animals which comprises administering a combination of two or more compounds selected from the group consisting of an inhibitor of 5.alpha.-reductase activity, an anti-estrogen, an inhibitor of aromatase activity, an inhibitor of 17.beta.-hydroxysteroid dehydrogenase activity and, in some cases, an anti-androgen and/or an LHRH agonist. Pharmaceutical compositions

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useful for such treatment and pharmaceutical kits containing such compositions are disclosed. Excerpt(s): This invention relates to a method of prophylaxis and/or treatment of benign prostatic hyperplasia (BPH) in susceptible warm-blooded animals including man and in particular to a combination therapy involving administering a combination of drugs which inhibit sex steroid (androgens and estrogens) activity by blocking their formation and/or by blocking receptors where they act. The role of androgens in the development of benign prostatic hyperplasia in men is well documented (Wilson, N. Engl. J. Med. 317: 628-629, 1987). In fact, benign prostatic hyperplasia does not develop in the absence of the testes (referred to in Wendel et al., J. Urol. 108: 116-119, 1972). Blockade of testicular androgen secretion by surgical or medical (LHRH agonist) castration is known to decrease prostatic size (Auclair et al., Biochem. Biophys. Res. Commun. 76: 855-862, 1977; Auclair et al., Endocrinology 101: 1890-1893, 1977; Labrie et al., Int. J. Andrology, suppl. 2 (V. Hansson, ed.), Scriptor Publisher APR, pp. 303-318, 1978; Labrie et al., J. Andrology 1: 209-228, 1980; Tremblay and Belanger, Contraception 30: 483-497, 1984; Tremblay et al., Contraception 30: 585-598, 1984; Dube et al., Acta Endocrinol. (Copenh) 116: 413-417, 1987; Lacoste et al., Mol. Cell. Endocrinol. 56: 141147, 1988; White, Ann. Surg. 22: 1-80, 1895; Faure et al., Fertil. Steril. 37: 416-424, 1982; Labrie et al., Endocrine Reviews 7: 67-74, 1986; Huggins and Stevens, J. Urol. 43: 705-714, 1940; Wendel et al., J. Urol. 108: 116-119, 1972; Peters and Walsh, N. Engl. J. Med. 317: 599-604, 1987; Gabrilove et al., J. Clin. Endocrinol. Metab. 64: 1331-1333, 1987). Web site: http://www.delphion.com/details?pn=US06423698__ •

Combination therapy for the treatment of benign prostatic hyperplasia Inventor(s): Broten; Theodore P. (Ambler, PA), Nichtberger; Steven A. (Gladwyne, PA), Siegl; Peter K. S. (Blue Bell, PA) Assignee(s): Merck & Co., Inc. (Rahway, NJ) Patent Number: 6,410,554 Date filed: March 23, 1999 Abstract: This invention relates to combination therapy for the treatment of benign prostatic hyperplasia comprising an alpha-1a antagonist and an endothelin antagonist. More specifically, the use of a selective alpha-1a adrenergic receptor antagonist in combination with a subtype non-selective endothelin antagonist provides relief of lower urinary tract symptoms in patients with symptomatic prostatism or benign prostatic hyperplasia. This combination therapy improves lower urinary tract symptoms including increasing urine flow rate, decreasing residual urine volume and improving overall obstructive and irritative symptoms in patients with benign prostatic hyperplasia or symptomatic prostatism. Excerpt(s): The present invention provides combination therapy for the treatment of benign prostatic hyperplasia. More particularly, the combination comprises an alpha-1a adrenergic receptor antagonist with an endothelin antagonist, and optionally a 5areductase inhibitor, for relief of lower urinary tract symptoms in patients with symptomatic prostatism or benign prostatic hyperplasia. Benign prostatic hyperplasia, also known as benign prostatic hypertrophy or BPH, is an illness typically affecting men over fifty years of age, increasing in severity with increasing age. The symptoms of the condition include, but are not limited to, increased difficulty in urination and sexual dysfunction. These symptoms are induced by enlargement, or hyperplasia, of the

Patents 155

prostate gland. As the prostate increases in size, it impinges on free-flow of fluids through the male urethra. Concommitantly, the increased noradrenergic innervation of the enlarged prostate leads to an increased adrenergic tone of the bladder neck and urethra, further restricting the flow of urine through the urethra. Bladder outlet obstruction (BOO) in BPH patients results from a static component of increased prostatic mass which physically impinges on the urethra and a dynamic component of increased contractile tone of the prostatic-urethral smooth muscle. Standard treatment of BPH involves surgical or pharmacological intervention. Surgical intervention, either by removal of the prostate via radical prostatectomy or removing the prostatic adenoma via transurethral resection of the prostate alleviates both the static and dynamic components of BOO since the entire prostate or the majority of the prostatic smooth muscle is removed. Although these procedures result in the most marked improvement in symptoms, there is the possibility of mortality and morbidity since these are invasive surgical procedures. Many patients suffer incontinence and retrograde ejaculation as a consequence of these surgical procedures. Because of the chances for morbidity and mortality, these procedures are not optimum for patients with mild to moderate symptoms in a disease which is not life-threatening. Web site: http://www.delphion.com/details?pn=US06410554__ •

Dihydropyrimidines and uses thereof Inventor(s): Cui; Donghui (Newtown, PA), Davis; Margaret R. (Redmond, WA), Dunn; Michael (Cambridge, MA), Evans; Ben E. (Lansdale, PA), Kari; Hanumath P. (Hatfield, PA), Lagu; Bharat (Maywood, NJ), Nagarathnam; Dhanapalan (Bethany, CT), Vyas; Kamlesh P. (North Wales, PA), Zhang; Kanyin (San Diego, CA) Assignee(s): Synaptic Pharmaceutical Corporation (Paramus, NJ) Patent Number: 6,680,323 Date filed: June 4, 2001 Abstract: This invention is directed to dihydropyrimidines which are selective antagonists for human.alpha.sub.1a receptors. This invention is also related to uses of these compounds for relaxing lower urinary tract tissue, treating benign prostatic hyperplasia and for the treatment of any disease where the antagonism of the.alpha.sub.1a receptor may be useful. The invention further provides a pharmaceutical composition comprising a therapeutically effective amount of the abovedefined compounds and a pharmaceutically acceptable carrier. Excerpt(s): Throughout this application, various references are referred to within parentheses. Disclosures of these publications in their entireties are hereby incorporated by reference into this application to more fully describe the state of the art to which this invention pertains. Benign Prostatic Hyperplasia (BPH), also called Benign Prostatic Hypertrophy, is a progressive condition which is characterized by a nodular enlargement of prostatic tissue resulting in obstruction of the urethra. This results in increased frequency of urination, nocturia, a poor urine stream and hesitancy or delay in starting the urine flow. Chronic consequences of BPH can include hypertrophy of bladder smooth muscle, a decompensated bladder and an increased incidence of urinary tract infection. The specific biochemical, histological and pharmacological properties of the prostate adenoma leading to the bladder outlet obstruction are not yet known. However, the development of BPH is considered to be an inescapable phenomenon for the aging male population. BPH is observed in approximately 70% of males over the age of 70. Currently, in the United States, the method of choice for treating BPH is surgery

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(Lepor, H., Urol. Clinics North Amer., 17, 651 (1990)). Over 400,000 prostatectomies are performed annually (data from 1986). A medicinal alternative to surgery is clearly very desirable. The limitations of surgery for treating BPH include the morbidity rate of an operative procedure in elderly men, persistence or recurrence of obstructive and irritative symptoms, as well as the significant cost of surgery.alpha.-Adrenergic receptors (McGrath, et. al. Med. Res. Rev., 9, 407-533, 1989) are specific neuroreceptor proteins located in the peripheral and central nervous systems on tissues and organs throughout the body. These receptors are important switches for controlling many physiological functions and, thus, represent important targets for drug development. In fact, many.alpha.-adrenergic drugs have been developed over the past 40 years. Examples include clonidine, phenoxybenzamine and prazosin (treatment of hypertension), naphazoline (nasal decongestant), and apraclonidine (treating glaucoma).alpha.-Adrenergic drugs can be broken down into two distinct classes: agonists (clonidine and naphazoline are agonists), which mimic the receptor activation properties of the endogenous neurotransmitter norepinephrine, and antagonists (phenoxybenzamine and prazosin are antagonists), which act to block the effects of norepinephrine. Many of these drugs are effective but also produce unwanted side effects (for example, clonidine produces dry mouth and sedation in addition to its antihypertensive effects). Web site: http://www.delphion.com/details?pn=US06680323__ •

Dual mode transurethral microwave warming apparatus Inventor(s): Carr; Kenneth L. (Harvard, MA), Regan; James F. (Waltham, MA) Assignee(s): Meridian Medical Systems, LLC (Ayer, MA) Patent Number: 6,424,869 Date filed: January 3, 2000 Abstract: A dual mode transurethral warming apparatus particularly adapted to treat benign prostatic hyperplasia includes a urethral catheter dimensioned for insertia through the urethra. The catheter includes an elongated flexible tube having a plurality of longitudinal lumens extending between the ends of the tube. A coaxial cable extends along one of the lumens to an antenna in the form of a multi-turn helical winding wound around the outside of the tube. A first connector connects one of the cable conductors to one end of the winding and a second connector connects the other cable conductor to the other end of the winding so that the antenna formed by the winding is larger in diameter than the cable, and all of the lumens are located within the winding. The cable is connected to a control and display unit which includes a transmitter which provides electromagnetic energy via the cable to the antenna so that the antenna generates an electromagnetic field sufficient to treat tissue adjacent the antenna. The same antenna also detects thermal energy emitted by the tissue thereby developing an electrical signal which is fed via the cable to a receiver in the form of a radiometer in the control and display unit. The cable is connected to the transmitter and receiver by way of a diplexer which separates the transmitter and receiver signal frequencies allowing the use of the common coaxial cable and antenna for both heating the tissue and sensing the actual temperature of the tissue. Preferably, the catheter includes an inflatable balloon at the distal end of the tube, the balloon being inflated by flowing an inflation fluid to the balloon via one of the lumens in the tube. Other working lumens may be included in the tube for providing drainage and for coolant circulation to cool the exterior surfaces of the catheter.

Patents 157

Excerpt(s): This application relates to transurethral hypothermia apparatus. It relates more particularly to a dual mode (i.e heating and sensing) transurethral microwave warming apparatus. It is well known that heat can be used to reduce an enlarged prostate. Benign prostatic hyperplasia (BPH) is a common disease among aging men that may lead to several complications such as urinary tract infection, acute urinary retention or uremia. In the U.S. alone, there are approximately 400,000 transurethral resection procedures performed each year involving general anesthesia and hospitalization to treat the above problem. Many patients are poor surgical risks due to age and possible co-existing health problems. Microwave hyperthermia appears to be a practical alternative to transurethral resection for the prostate, the usual surgical procedure. Microwave transurethral hyperthermia involves insertion of a small catheter, including a microwave antenna, into the bladder via the urethra. This procedure can be performed in an outpatient basis without the need for general anesthesia. Web site: http://www.delphion.com/details?pn=US06424869__ •

Forms of free prostate-specific antigen (PSA) and their association with prostate tissues from prostate peripheral zone and transition zone Inventor(s): Mikolajczyk; Stephen D. (San Diego, CA), Rittenhouse; Harry G. (Del Mar, CA), Slawin; Kevin (Houston, TX), Wang; Tang Jang (Poway, CA), Wolfert; Robert L. (San Diego, CA) Assignee(s): Baylor College of Medicine (Houston, TX), Hybritech Incorporated (Fullerton, CA) Patent Number: 6,423,503 Date filed: April 30, 1999 Abstract: A method of distinguishing prostate cancer from benign prostatic hyperplasia (BPH) is provided. The mathematical combination or ratio of proPSA and BPSA serum or tissue markers may be used for distinguishing benign prostatic hyperplasia (BPH) from prostate cancer. It is the discovery of the present invention that BPSA is preferentially elevated in transition zone prostate tissue whereas pPSA is elevated in the peripheral zone of prostate tissue. A kit for aiding in distinguishing BPH from prostate cancer is also provided. Excerpt(s): The invention relates generally to prostate-specific antigen (PSA) and specifically to different forms of PSA and their association with prostate cancer and benign prostate disease. Throughout this application, various references are referred to within parentheses. Disclosures of these publications in their entireties are hereby incorporated by reference into this application to more fully describe the state of the art to which this invention pertains. Full bibliographic citation for these references may be found at the end of this application, preceding the claims. The measurement of serum PSA is a widely used marker for the early detection of human prostate cancer (1-3). Elevated levels of PSA in the blood are symptomatic of prostate disease, which is primarily manifested as either benign prostate hyperplasia (BPH) or prostate cancer (PCa). However, in the range 4-10 ng PSA per ml of serum it is difficult to distinguish BPH from PCa without additional tests such as digital rectal exam and prostate needle biopsy. Web site: http://www.delphion.com/details?pn=US06423503__

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Forms of prostate specific antigen (PSA) specific for benign prostatic hyperplasia (BPH) and methods of using such Inventor(s): Mikolajczyk; Stephen D. (San Diego, CA), Rittenhouse; Harry G. (Del Mar, CA), Slawin; Kevin (Houston, TX), Wang; Tang Jang (Poway, CA), Wolfert; Robert L. (San Diego, CA) Assignee(s): Hybritech Incorporated (San Diego, CA) Patent Number: 6,482,599 Date filed: April 30, 1999 Abstract: A substantially pure and isolated novel form of prostate specific antigen (PSA) is provided. The novel form of PSA of the present invention comprises at least one clip at Lys 182 of the amino acid sequence of a mature form of PSA. Preferably, the novel form of PSA additionally comprises one or more clips at a location selected from a group consisting of Ile 1, Lys 145, and Lys 146. More preferably, the form of PSA contains at least two clips at Lys 145 and Lys 182 of the amino acid sequence of a mature form of PSA. The novel forms of PSA exist at an elevated level in patients suspected of having benign prostatic hyperplasia (BPH) and therefore may be used as a serum mark or an immunohistological marker to help distinguish BPH from prostate cancer. Antibodies recognizing the novel forms of PSA and immunoassays that detect and determine the novel forms of PSA of the present invention in a sample are also provided. Further provided are a kit and a method for detecting the novel forms of PSA for aiding in the differentiation of prostate cancer from BPH. Excerpt(s): The invention relates generally to prostate specific antigen (PSA) and specifically to new forms of PSA that are specific for benign prostatic hyperplasia and methods of using the new forms of PSA. Throughout this application, various references are referred to within parentheses. Disclosures of these publications in their entireties are hereby incorporated by reference into this application to more fully describe the state of the art to which this invention pertains. Full bibliographic citation for these references may be found at the end of this application, preceding the claims. Prostate cancer is the most frequently diagnosed cancer in American males. Prostate specific antigen (PSA) has been widely used as a reliable prognostic marker in the management of patients with prostate cancer (1-3). PSA is a member of the human kallikrein family of serine proteases (extensively reviewed in (4)). It is a serine endopeptidase with chymotrypsin-like enzymatic activity. The mature form of PSA (identified as SEQ ID NO:1) has isoleucine as the N-terminal and 237 amino acid residues with a molecular mass of 28,400 D (5; 6). Web site: http://www.delphion.com/details?pn=US06482599__

•

Immunoassay for quantitative determination of the complex between prostate specific antigen (PSA) and.alpha.2-macroglobulin (A2M) in a sample Inventor(s): Stenman; Ulf-H.ang.kan (Heikelsvagen 10, Grankulla, FI) Assignee(s): none reported Patent Number: 6,632,623 Date filed: January 10, 2001 Abstract: This invention concerns an immunoassay for quantitative determination of the amount of the complex (PSA-A.sub.2 M) between prostate specific antigen (PSA)

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and.alpha.sub.2 -macroglobulin (A.sub.2 M) in a sample. The assay comprises the steps of removing immunoreactive PSA from the sample, treating the PSA-A.sub.2 M complex in the remaining supernatant so as to make the PSA thereof immunoreactive, determining the immunoreactive PSA derived from the PSA-A.sub.2 M complex by exposing it to an antibody which binds immunoreactive PSA, and detecting the PSA. The invention also concerns a method for differentiating patients with cancer of the prostate (PCa) from patients with benign prostatic hyperplasia (BPH) or healthy male subjects without PCa, wherein the individual's body fluid concentration of PSA has been determined as free PSA and as total PSA. The method is characterized in that PSA complexed with A.sub.2 M (PSA-A.sub.2 M) in the individual's serum sample has been determined, and that the ration between PSA-A.sub.2 M and other forms of PSA is calculated, or that the diagnostic value is calculated by logistic regression, neural networks, fussy logic or similar mathematical and statistical methods using PSA-A.sub.2 M and other forms of PSA, such as total PSA, free PSA and PSA-ACT as input variables. Excerpt(s): This invention relates to an immunoassay for the quantitative determination of the amount of the complex (PSA-A.sub.2 M) between prostate specific antigen (PSA) and.alpha.sub.2 -macroglobulin (A.sub.2 M) in a serum sample. The invention relates further to an improved method for differentiating patients with cancer of the prostate (PCa) from patients with benign prostatic hyperplasia (BPH) or healthy male subjects without PCa. The publications and other materials used herein to illuminate the background of the invention, and in particular, cases to provide additional details respecting the practice, are incorporated by reference. In the following description, the abbreviation "PSA" means prostate-specific antigen; A.sub.2 M.alpha.sub.2 macroglobulin; PSA-A.sub.2 M complex between PSA and A.sub.2 M; ACT.alpha.sub.1 antichymotrypsin; PSA-ACT complex between PSA and ACT; API.alpha.sub.1 -protease inhibitor; PSA-API complex between PSA and API; MAb monoclonal antibody; BSA bovine serum albumin; TBS 50 mmol/L Tris-HCl buffer, pH 7.4 containing 150 mmol/L sodium chloride and 8 mmol/L sodium azide; IFMA immunofluorometric assay; SDS sodium dodecyl sulfate; SDS-PAGE: SDS polyacrylamide gel electrophoresis; BPH benign prostatic hyperplasia; PCa prostate cancer; CV coefficient variation; ROC receiver operating characteristic; AUC area under the curve; and sandwich assay for PSA-A.sub.2 M a sandwich assay using a monoclonal anti-PSA antibody as catcher and a labelled antibody to A.sub.2 M for detection. Web site: http://www.delphion.com/details?pn=US06632623__ •

Method of constructing a microwave antenna Inventor(s): Arndt; G. Dickey (Friendswood, TX), Carl; James (Houston, TX), Ngo; Phong (Friendswood, TX) Assignee(s): The United States of America as represented by the Administrator of the (Washington, DC) Patent Number: 6,512,956 Date filed: December 18, 2000 Abstract: A method, simulation, and apparatus are provided that are highly suitable for treatment of benign prostatic hyperplasia (BPH). A catheter is disclosed that includes a small diameter disk loaded monopole antenna surrounded by fusion material having a high heat of fusion and a melting point preferably at or near body temperature. Microwaves from the antenna heat prostatic tissue to promote necrosing of the prostatic tissue that relieves the pressure of the prostatic tissue against the urethra as the body

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reabsorbs the necrosed or dead tissue. The fusion material keeps the urethra cool by means of the heat of fusion of the fusion material. This prevents damage to the urethra while the prostatic tissue is necrosed. A computer simulation is provided that can be used to predict the resulting temperature profile produced in the prostatic tissue. By changing the various control features of the catheter and method of applying microwave energy a temperature profile can be predicted and produced that is similar to the temperature profile desired for the particular patient. Excerpt(s): The present invention relates to apparatus, methods, and computer simulations highly suitable for treatment of benign prostatic hyperplasia (BPH) and, more particularly, to a unique catheter for microwave treatment of BPH to necrose prostatic tissue while protecting urethral tissue and computer simulations relating to the same. Benign prostatic hypertrophy or hyperplasia (BPH) is one of the most common medical problems experienced by men over 50 years old. Urinary tract obstruction due to prostatic hyperplasia has been recognized since the earliest days of medicine. Hyperplastic enlargement of the prostate gland, or enlargement due to abnormal but benign multiplication of the cells thereof, often leads to compression of the urethra thereby resulting in obstruction of the urinary tract. Common symptoms that develop from this condition may include more frequent urination, decrease in urinary flow, nocturia, pain, and discomfort. The incidence of BPH in men over 50 years of age is approximately 50 percent and increases to over 75 percent in men over 80 years of age. Symptoms of urinary obstruction occur most frequently between the ages of 65 and 70 when approximately 65 percent of men in the age group have prostatic enlargement. When treatment by drug therapy is not sufficiently effective, surgical procedures for treating BPH are available but have potential side effects. General surgical risks apply such as anesthesia related morbidity, hemorrhage, coagulopathies, pulmonary emboli, electrolyte imbalance, and the like. Other problems that may occur from surgical correction include cardiac complications, bladder perforation, incontinence, infection, urethral or bladder neck stricture, retention of prostatic chips, and infertility. Due to the problems of surgery, many or even most patients delay treatment. However, the delay of treatment may lead to other complications including obstructive lesion in the prostate, chronic infection, and the like. Therefore it is unquestionable that a need exists for improved surgical or non-surgical methods for treating BPH. Web site: http://www.delphion.com/details?pn=US06512956__ •

Method of treating androgen-dependent disorders Inventor(s): Bond; Richard W. (Union, NJ), Pachter; Jonathan A. (Maplewood, NJ), Wang; Lynn (Fanwood, NJ) Assignee(s): Schering Corporation (Kenilworth, NJ) Patent Number: 6,710,037 Date filed: May 1, 2002 Abstract: Novel methods of treating subjects afflicted with an androgen-dependent disorder, such as prostate cancer and benign prostatic hyperplasia are disclosed. Specifically, methods of treating androgen-dependent disorders by introducing a polypeptide or a polynucleotide encoding the polypeptide, which enhances inactivation of active androgens, are described. Excerpt(s): All references cited herein are incorporated in their entirety by reference. The present invention relates to methods of using polypeptides or polynucleotides that

Patents 161

encode polypeptides which enhance inactivation of active androgens for the treatment of androgen-dependent disorders. Specifically, the present invention relates to methods of treating conditions wherein androgen activity is implicated such as prostate cancer, benign prostatic hyperplasia and other androgen-dependent disorders such as androgenic alopecia. An androgen-dependent disorder refers to any disorder that can benefit from a decrease in androgen stimulation and includes pathological conditions that depend on androgen stimulation. An androgen-dependent disorder can result from an excessive accumulation of testosterone or other androgenic hormone; increased sensitivity of androgen receptors to androgen; or an increase in androgen-stimulated transcription. Examples of androgen-dependent disorders include prostate cancer, benign prostatic hyperplasia, acne vulgaris, seborrhea, female hirsutism, androgenic alopecia (which includes female and male pattern baldness), and polycystic ovary syndrome. Early attempts to provide a chemotherapeutic agent to counter the undesirable results of androgen-dependent disorders resulted in the discovery of several steroidal antiandrogens having undesirable hormonal activities of their own. The estrogens, for example, not only counteract the effect of the androgens but have a feminizing effect as well. Non-steroidal antiandrogens have also been developed, for example, 4'-nitro-3'-trifluoromethyl-isobutyranilide. See Neri et al., "A Biological Profile of a Nonsteroidal Antiandrogen, SCH 13521 (4'-Nitro-3'Trifluoromethylisobutyranilide)", Endocrinology, 91(2):427-437 (1972). Unfortunately, even though these products are largely devoid of direct hormonal stimulatory effects, they compete with all natural androgens for receptor sites. Hence these products have a tendency to feminize a male host or the male fetus of a female host and/or initiate feedback effects that cause hyperstimulation of the testes with increased androgen production. Web site: http://www.delphion.com/details?pn=US06710037__ •

Method of treating benign prostatic hyperplasia and other benign prostate conditions Inventor(s): Parks; L. Dean (2420 SE. 15th St., Ocala, FL 34471) Assignee(s): none reported Patent Number: 6,733,779 Date filed: September 17, 2001 Abstract: Methods of treatment of benign prostatic hyperplasia and reduction of the level of the prostate specific antigen (PSA) of benign prostate conditions are disclosed. The treatment method includes an initial treatment of patients with orally administration of an initial dosage of about 40 mg 13 cis-retinoic acid daily for a period from about ten days to about twenty days, and followed by a sustaining treatment of the patients with orally administration of a sustaining dosage of about 40 mg 13 cis-retinoic acid about every five to seven days in a sustaining period. Excerpt(s): The present invention relates to methods for treating benign prostate hyperplasia and reducing the level of prostate specific antigen of benign prostate conditions. More specifically, the methods utilize 13 cis-retinoic acid to effectively treat benign prostate hyperplasia, and to reduce the level of prostate specific antigen of the patients with benign prostate conditions. The three most common prostate health problems facing men and their families today are benign prostatic hyperplasia (BPH), prostate cancer, and prostatitis. Each of these conditions affects the prostate differently. Benign prostate hyperplasia is the most common benign neoplasm (non cancerous enlargement of the prostate gland) in men, and has a high prevalence that increases with

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age. The increase in size of the prostate inside its capsule exerts pressure on the urethra, which passes through the capsule, resulting in obstruction to urine flow. Half of all men have BPH identifiable histologically at age 60 years, and by 85 years the prevalence is about 90%. In the United States about 25% of men will be treated for BPH by age 80, and over 300,000 surgical procedures are performed each year for BPH (mostly transurethral resection of the prostate, TURP). This makes TURP the second most common surgical procedure, second only to cataract surgery--at a cost estimated at $2 billion per year. Experts do not yet know what causes BPH, but the condition may be related to the hormone testosterone and its relationship to other hormones that change during the aging process. There are a number of treatment options for BPH. These include watchful waiting, medical therapy such as alpha blocker therapy and finasteride therapy, balloon dilatation and various surgical procedures such as transurethral incision of the prostate (TUIP), transurethral resection of the prostate (TURP), and open prostatectomy. Few treatments are without any adverse consequences, and this is particularly so with treatments with BPH, where there is a delicate balancing act between the benefits and demerits of the treatments available. The adverse events following treatment for BPH include impotence (for various surgical procedures ranging from about 4% to 40%, the incidence of impotence is also increased after some medical treatments), incontinence (stress incontinence about 3% after surgery, with total urinary incontinence approaching 1%), and the need for re-treatment. Combined analysis of published data estimated that the mean probability for perioperative mortality (death within 90 days of a procedure) was 1.5% for TURP. For open surgery it was 2.4% and for balloon dilation it was 3.5%. Web site: http://www.delphion.com/details?pn=US06733779__ •

Thienopyranecarboxamide derivatives Inventor(s): Leonardi; Amedeo (Milan, IT), Motta; Gianni (Barlassina, IT), Riva; Carlo (Varese, IT), Testa; Rodolfo (Vignate, IT) Assignee(s): Recordati S.A. Chemical and Pharmaceutical Company (Chiasso, CH) Patent Number: 6,387,909 Date filed: July 28, 2000 Abstract: The invention relates to novel N-(substituted phenyl)-N'-[.omega.-(5substituted-7-oxo-7H-thieno[3,2-b]pyran-3-carbonyla mino)alkyl]piperazines their Noxides and pharmaceutically acceptable salts thereof. The compounds are endowed with enhanced selectivity for alpha1-adrenergic receptors and a low activity in lowering blood pressure. The compounds are useful in the treatment of obstructive syndromes of the lower urinary tract, including benign prostatic hyperplasia (BPH), and in the treatment of lower urinary tract symptoms (LUTS) and neurogenic lower urinary tract dysfunction (NLUTD). The compounds are also useful in the treatment of excessive intraocular pressure, cardiac arrhythmia, erectile dysfunction, sexual dysfunction, and for inhibiting cholesterol synthesis or reducing sympathetically mediated pain. Excerpt(s): The present invention relates to thienopyranecarboxamide derivatives, to pharmaceutical compositions containing them and to uses for such derivatives and compositions. 7-Oxo-7H-thieno[3,2-b]pyran-3-carboxylic acid and its N,.omega.aminoalkylamides are compounds not yet reported in the literature. The present invention is directed to the new structural class of the N-(substituted phenyl)-N'[.omega.-(5-substituted-7-oxo-7H-thieno[3,2-b]pyran-3-carbonyla mino)alkyl]piperazines. Compounds of this class are endowed with enhanced selectivity toward the.alpha.sub.1 adrenergic receptor, in particular with respect to the 5-

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HT.sub.1A receptor, and improved in vivo uroselectivity even compared to compound A, with remarkable effects on relaxation of prostatic urethra and very low activity in lowering blood pressure. This activity profile suggests the safer use of the compounds of the invention in the therapy of obstructive syndromes of the lower urinary tract, including benign prostatic hyperplasia (BPH), without side-effects associated with hypotensive activity. Web site: http://www.delphion.com/details?pn=US06387909__ •

Use of.alpha.1C specific compounds to treat benign prostatic hyperplasia Inventor(s): Branchek; Theresa A. (Teaneck, NJ), Chiu; George (Bridgewater, NJ), Forray; Carlos C. (Paramus, NJ), Gluchowski; Charles (Danville, CA), Hartig; Paul R. (Pennington, NJ), Wetzel; John M. (Elmwood Park, NJ) Assignee(s): Synaptic Pharmaceutical Corporation (Paramus, NJ) Patent Number: 6,602,888 Date filed: November 22, 1999 Abstract: A method of treating benign prostatic hyperplasia in a subject which comprises administering to the subject a therapeutically effective amount of a compound which binds to a human.alpha.sub.1C adrenergic receptor with a binding affinity greater than ten-fold higher than the binding affinity with which the compound binds to a human.alpha.sub.1A adrenergic receptor, a human.alpha.sub.1B adrenergic receptor, and a human histamine H.sub.1 receptor, and, binds to a human.alpha.sub.2 adrenergic receptor with a binding affinity which is greater than ten-fold lower than the binding affinity with which the compound binds to such.alpha.sub.1C adrenergic receptor. Compounds meeting these criteria are provided. Excerpt(s): Benign Prostatic Hyperplasia (BPH), also called Benign Prostatic Hypertrophy, is a progressive condition which is characterized by a nodular enlargement of prostatic tissue resulting in obstruction of the urethra. This results in increased frequency of urination, nocturia, a poor urine stream and hesitancy or delay in starting the urine flow. Chronic consequences of BPH can include hypertrophy of bladder smooth muscle, a decompensated bladder and an increased incidence of urinary tract infection. The specific biochemical, histological and pharmacological properties of the prostate adenoma leading to the bladder outlet obstruction are not yet known. However, the development of BPH is considered to be an inescapable phenomenon for the aging male population. BPH is observed in approximately 70% of males over the age of 70. Currently, in the United States, the method of choice for treating BPH is surgery (Lepor, H. Urol. Clinics North Amer., 17, 651 (1990)). Over 400,000 prostatectomies are performed annually (data from 1986). A medicinal alternative to surgery is clearly very desirable. The limitations of surgery for treating BPH include the morbidity rate of an operative procedure in elderly men, persistence or recurrence of obstructive and irritative symptoms, as well as the significant cost of surgery.alpha.-Adrenergic receptors are specific neuroreceptor proteins located in the peripheral and central nervous systems on tissues throughout the body. These receptors are important switches for controlling many physiological functions and, thus, represent important targets for drug development. In fact, many.alpha.-adrenergic drugs have been developed over the past 40 years. Examples include clonidine, phenoxybenzamine and prazosin (treatment of hypertension), naphazoline (nasal decongestant), and apraclonidine (treating glaucoma).alpha.-Adrenergic drugs can be broken down into two distinct classes: agonists (clonidine and naphazoline are agonists), which mimic the

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receptor activation properties of the endogenous neurotransmitter norepinephrine, and antagonists (phenoxybenzamine and prazosin are antagonists), which act to block the effects of norepinephrine. Many of these drugs are effective but also produce unwanted side effects (for example, clonidine produces dry mouth and sedation in addition to its antihypertensive effects). During the past 15 years a more precise understanding of.alpha.-adrenergic receptors and their drugs has evolved through increased scientific scrutiny. Prior to 1977, only one.alpha.-adrenergic receptor was known to exist. Between 1977 and 1988, it was accepted by the scientific community that at least two.alpha.adrenergic receptors--.alpha.sub.1 and.alpha.sub.2 --existed in the central and peripheral nervous systems. Since 1988, new techniques in molecular biology have led to the identification of at least six.alpha.-adrenergic receptors which exist throughout the central and peripheral nervous systems:.alpha.sub.1A,.alpha.sub.1B,.alpha.sub.1C,.alpha.sub.2A,.alpha.sub.2B and.alpha.sub.2C (Bylund, D. B., FASEB J., 6, 832 (1992)). It is not known precisely which physiological responses in the body are controlled by each of these receptors. In addition, many.alpha.-adrenergic drugs that were developed before 1992 are not selective for any particular.alpha.-adrenergic receptor. Many of these drugs produce untoward side effects which may be attributed to their poor.alpha.-adrenergic receptor selectivity. Web site: http://www.delphion.com/details?pn=US06602888__

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

Altered intracellular localization of BRK/Sik protein tyrosine kinase in human prostate tumors Inventor(s): Derry, Jason J.; (Aurora, IL), Tyner, Angela; (Chicago, IL) Correspondence: Kevin E. Noonan; Mcdonnell Boehnen Hulbert & Berghoff; 32nd Floor; 300 S. Wacker Drive; Chicago; IL; 60606; US Patent Application Number: 20030148358 Date filed: January 13, 2003 Abstract: The invention provides methods for detecting abnormal prostate conditions, such as benign prostatic hyperplasia (BPH), prostatic intraepithelial neoplasia (PIN), and adenocarcinoma, in an animal by comparing the amount of the Breast Tumor Kinase (BRK) tyrosine kinase in the nuclei of prostate luminal epithelial cells in a test sample with an amount of nuclear BRK protein in epithelial cells of normal prostate glands. Excerpt(s): This application is related to U.S. provisional application Serial No. 60/347,720,filed Jan. 11, 2002. This invention was developed under a grant from the National Institutes of Health (grant number DK44525). The U.S. government may have certain rights to this invention. The invention relates to methods for detecting an

9

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

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abnormal prostate condition in an animal. Specifically, the invention relates to methods of detecting an abnormal prostate condition in an animal by detecting the amount of Breast Tumor Kinase (BRK) protein present in the nuclei of prostate luminal epithelial cells within a prostate tissue sample compared with the amount of BRK protein in the nuclei of normal prostate luminal epithelial cells. The invention further relates to methods for detecting prostate cancer in an animal by identifying prostate tissue samples wherein luminal epithelial cells in the sample do not display BRK nuclear localization. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Apparatus and method for the treatment of benign prostatic hyperplasia Inventor(s): Chornenky, Victor I.; (Minnetonka, MN), Jaafar, Ali; (Eden Prairie, MN) Correspondence: Ali Jaafar; 11600 Landing Road; Eden Prairie; MN; 55347; US Patent Application Number: 20040059389 Date filed: September 23, 2003 Abstract: An apparatus and method for treatment of benign prostatic hyperplasia is disclosed wherein the apparatus includes an applicator having a probe having proximal and distal probe sections wherein the proximal and distal probe sections each define an axis and wherein the axes are not collinear. Excerpt(s): The present application claims priority to U.S. Provisional Application No. 60/412,705 entitled "Apparatus and method for treatment of benign prostatic hyperplasia by electroporation", which was filed Sep. 23, 2002. This application also claims priority to U.S. patent application Ser. No. 10/217,749 entitled "Apparatus and method for treatment of benign prostatic hyperplasia by electroporation", which was filed Aug. 13, 2002 (U.S. Patent Application Publication 2003/0060856, published Mar. 27, 2003). The present invention relates generally to methods and apparatus for the electroporation of tissues and more specifically to such methods and apparatus for the treatment of benign prostatic hyperplasia. The biophysical phenomenon known as electroporation refers to the use of electric field pulses to induce microscopic pores-"electropores"--in the lipid cell membranes. Depending on the parameters of the electric pulses, an electroporated cell can survive the pulsing or die. The cause of death of an electroporated cell is believed to be a chemical imbalance in the cell, resulting from the fluid communication with the extra-cellular environment through the pores. For a given cell size, geometry, and orientation, the number of electropores--and their size--created in the cell by the applied electric field pulses depends on both the amplitude E of the electric field pulses and the duration t of the pulses. That is, for a given pulse duration t, no pores will be induced in the cell until the amplitude E reaches a certain lower limit. This limit is different for different cells, particularly, for cells of different sizes. The smaller the size of a cell, the higher the electric field required to induce pores and thus the higher the lower limit is. Above the lower amplitude E limit the number of pores and their effective diameter increases proportionally with both increasing field amplitude E and pulse duration t. Electroporation is observed for pulse durations in the range from tens of microseconds to hundreds of milliseconds. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Apparatus and method for treatment of benign prostatic hyperplasia Inventor(s): Chornenky, Victor; (Minnetonka, MN), Jaafar, Ali; (Eden Prairie, MN) Correspondence: Briggs And Morgan, P.A.; 2400 Ids Center; Minneapolis; MN; 55402; US Patent Application Number: 20030060856 Date filed: August 13, 2002 Abstract: An apparatus and a method for treatment of benign prostatic hyperplasia are disclosed. The apparatus includes an applicator piece carrying a set of electrodes shaped and positioned to create a substantial electric field in the volume of hyperplasia and a pulse generator adapted for delivery of electrical pulses above the upper electroporation limit for the neoplastic cells. The amplitude, duration and number of the electrical pulses are generally selected to cause necrosis of a significant fraction of the volume of benign prostatic hyperplasia. The apparatus may include a high frequency system for heating the prostatic tissue and a cooling system for cooling the urethra. The combined action of heating and cooling may increase the temperature of the prostate cells to 45.degree. C. to 55.degree. C., while keeping the urinary tract at a temperature 15.degree. C. to 20.degree. C. This temperature distribution can increase the selectivity of the treatment by increasing susceptibility of the neoplastic cells to the electroporation treatment and decreasing it for the normal urethral tissues. Excerpt(s): The present application claims priority to U.S. Provisional Application No. 60/311,792 entitled "Apparatus and method for treatment of benign prostatic hyperplasia by electroporation", which was filed Aug. 13, 2001. This application also claims priority to U.S. Provisional Application No. 60/325,994 entitled "Apparatus and method for treatment of benign prostatic hyperplasia by electroporation", which was filed Oct. 1, 2001. The present invention relates generally to the therapeutic treatment of tissues and more particularly, to an apparatus and method for therapeutic treatment of benign prostatic hyperplasia. Biophysical phenomenon "electroporation" (EP) refers to the use of electric field pulses to induce microscopic aquatic pores--"electropores"--in the lipid cell membranes. Depending on the parameters of the electric pulses, electroporated cell can survive the pulsing or die. The cause of death of an electroporated cell is believed to be a chemical imbalance in the cell, resulted from the fluid communication with the extra cellular environment through the pores. The number and size of electropores depend on both, the amplitude of electric field pulse E and the pulse duration t. Electroporation is observed for pulse durations in the range from tens of microseconds to hundreds of milliseconds. For a given duration of a pulse and bellow a certain limit of the electric field amplitude, no pores are induced at all. This limit is different for different cells, particularly, for cells of different sizes. The smaller the size of a cell, the higher the electric field required to induce pores and thus the higher the limit is. Above the lower limit the number of pores and their effective diameter increases proportionally with both the amplitude E and duration t. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

Patents 167

•

Bicyclic heterocycles, pharmaceutical compositions containing these compounds, their use and processes for the preparation thereof Inventor(s): Himmelsbach, Frank; (Mittelbiberach, DE), Jung, Birgit; (Mittelbiberach, DE), Solca, Flavio; (Wien, AT) Correspondence: Boehringer Ingelheim Corporation; 900 Ridgebury Road; P. O. Box 368; Ridgefield; CT; 06877; US Patent Application Number: 20040044014 Date filed: April 17, 2003 Abstract: The present invention relates to bicyclic heterocycles of general formula 1whereinR.sup.a, R.sup.b, R.sup.c, A, B, C, D, E and X are defined as in claim 1, the tautomers, the stereoisomers, the mixtures and the salts thereof, particularly the physiologically acceptable salts thereof with inorganic or organic acids which have valuable pharmacological properties, particularly an inhibitory effect on signal transduction mediated by tyrosine kinases, the use thereof for treating diseases, particularly tumoral diseases, as well as benign prostatic hyperplasia (BPH), diseases of the lungs and respiratory tract, and the preparation thereof. Excerpt(s): Benefit of U.S. Provisional Application Serial No. 60/387,021, filed on Jun. 7, 2002 is hereby claimed, and said Application is herein incorporated by reference. the tautomers, the stereoisomers, the mixtures and the salts thereof, particularly the physiologically acceptable salts thereof with inorganic or organic acids or bases which have valuable pharmacological properties, particularly an inhibitory effect on signal transduction mediated by tyrosine kinases, the use thereof for treating diseases, particularly tumoral diseases, as well as benign prostatic hyperplasia (BPH), diseases of the lungs and respiratory tract, and the preparation thereof. unless otherwise stated, said alkyl groups may be straight-chained or branched. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

•

Compositions comprising alpha-1C specific compounds Inventor(s): Branchek, Theresa A.; (Teaneck, NJ), Chiu, George; (Bridgewater, NJ), Forray, Carlos C.; (Paramus, NJ), Gluchowski, Charles; (Danville, CA), Hartig, Paul R.; (Pennington, NJ), Wetzel, John M.; (Elmwood Park, NJ) Correspondence: John P. White; Cooper & Dunham Llp; 1185 Avenue OF The Americas; New York; NY; 10036; US Patent Application Number: 20030022900 Date filed: June 28, 2002 Abstract: A method of treating benign prostatic hyperplasia in a subject which comprises administering to the subject a therapeutically effective amount of a compound which binds to a human.alpha.sub.1C adrenergic receptor with a binding affinity greater than ten-fold higher than the binding affinity with which the compound binds to a human.alpha.sub.1A adrenergic receptor, a human.alpha.sub.1B adrenergic receptor, and a human histamine H.sub.1 receptor, and, binds to a human.alpha.sub.2 adrenergic receptor with a binding affinity which is greater than ten-fold lower than the binding affinity with which the compound binds to such.alpha.sub.1C adrenergic receptor. Compounds meeting these criteria are provided.

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Excerpt(s): Benign Prostatic Hyperplasia (BPH), also called Benign Prostatic Hypertrophy, is a progressive condition which is characterized by a nodular enlargement of prostatic tissue resulting in obstruction of the urethra. This results in increased frequency of urination, nocturia, a poor urine stream and hesitancy or delay in starting the urine flow. Chronic consequences of BPH can include hypertrophy of bladder smooth muscle, a decompensated bladder and an increased incidence of urinary tract infection. The specific biochemical, histological and pharmacological properties of the prostate adenoma leading to the bladder outlet obstruction are not yet known. However, the development of BPH is considered to be an inescapable phenomenon for the aging male population. BPH is observed in approximately 70% of males over the age of 70. Currently, in the United States, the method of choice for treating BPH is surgery (Lepor, H. Urol. Clinics North Amer., 17, 651 (1990)). Over 400,000 prostatectomies are performed annually (data from 1986). A medicinal alternative to surgery is clearly very desirable. The limitations of surgery for treating BPH include the morbidity rate of an operative procedure in elderly men, persistence or recurrence of obstructive and irritative symptoms, as well as the significant cost of surgery.alpha.-Adrenergic receptors are specific neurcreceptor proteins located in the peripheral and central nervous systems on tissues throughout the body. These receptors are important switches for controlling many physiological functions and, thus, represent important targets for drug development. in fact, many.alpha.-adrenergic drugs have been developed over the past 40 years. Examples include clonidine, phenoxybenzamine and prazosin (treatment of hypertension), naphazoline (nasal decongestant), and apraclonidine (treating glaucoma).alpha.-Adrenergic drugs can be broken down into two distinct classes: agonists (clonidine and naphazoline are agonists), which mimic the receptor activation properties of the endogenous neurotransmitter norepinephrine, and antagonists (phenoxybenzamine and prazosin are antagonists), which act to block the effects of norepinephrine. Many of these drugs are effective but also produce unwanted side effects (for example, clonidine produces dry mouth and sedation in addition to its antihypertensive effects). During the past 15 years a more precise understanding of.alpha.-adrenergic receptors and their drugs has evolved through increased scientific scrutiny. Prior to 1977, only one.alpha.-adrenergic receptor was known to exist. Between 1977 and 1988, it was accepted by the scientific community that at least two.alpha.adrenergic receptors--.alpha.sub.1 and.alpha.sub.2--existed in the central and peripheral nervous systems. Since 1988, new techniques in molecular biology have led to the identification of at least six.alpha.-adrenergic receptors which exist throughout the central and peripheral nervous systems:.alpha.sub.1A,.alpha.sub.1B,.alpha.sub.1C,.alpha.sub.2A,.alpha.sub.2B and.alpha.sub.2C (Bylund, D. B., FASEB J., 6, 832 (1992)). It is not known precisely which physiological responses in the body are controlled by each of these receptors. In addition, many.alpha.-adrenergic drugs that were developed before 1992 are not selective for any particular.alpha.-adrenergic receptor. Many of these drugs produce untoward side effects which may be attributed to their poor.alpha.-adrenergic receptor selectivity. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

Patents 169

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Compounds useful in therapy Inventor(s): Blagg, Julian; (Sandwich, GB), Fray, Michael Jonathan; (Sandwich, GB), Lewis, Mark Llewellyn; (Sandwich, GB), Mathias, John Paul; (Sandwich, GB), Stefaniak, Mark Henryk; (Sandwich, GB), Stobie, Alan; (Sandwich, GB) Correspondence: Pfizer INC.; Patent Department, Ms8260-1611; Eastern Point Road; Groton; CT; 06340; US Patent Application Number: 20040029859 Date filed: March 12, 2003 Abstract: Compounds of formula (I): 1or pharmaceutically acceptable salts or solvates thereof, whereinR.sup.1 represents C.sub.1-4 alkyl;R.sup.2 represents halo, C.sub.1-4 alkyl, C.sub.3-6 cycloalkyl, C.sub.3-6 cycloalkyloxy, --SO.sub.2(C.sub.1-4 alkyl), optionally substituted C.sub.1-4 alkyloxy, Het or --OHet;R.sup.3 represents a bicyclic group of the formula 2 wherein X and Y are selected from C and N, provided that at least one is C;Ring A together with X and Y represents a 5- or 6-membered aromatic ring containing 0, 1, 2 or 3 nitrogen atoms in the ring; n is), 1 or 2L represents a direct link, C.sub.1-4 alkylene or C.sub.1-4 alkoxyalkylene;R.sup.4 represents H, --NR.sup.5R.sup.6, C.sub.3-6 cycloalkyl, --OR.sup.7, Het.sup.1 or Het.sup.4;R.sup.5 and R.sup.6 are independently selected from H, C.sub.3-6 cycloalkyl, C.sub.3-6 cycloalkyl-C.sub.1-4 alkylene, --SO.sub.2(C.sub.1-4 alkyl) and optionally substituted C.sub.1-4 alkylR.sup.7 is selected from H, C.sub.1-4 alkyl, C.sub.1-4 alkoxyalkyl, C.sub.3-6cycloalkyl, Het.sup.2 and C.sub.1-4alkyl-Het.sup.3;R.sup.8 is H or C.sub.1-4 alkyl;Het, Het.sup.1, Het.sup.2 and Het.sup.3 independently represent an optionally substituted 4 to 7 membered saturated heterocyclic group which may be mono- or bi-cyclic and which contains one or more heteroatoms selected from N, O or S;Het.sup.4 represents an optionally substituted 5 or 6 membered unsaturated heterocyclic group containing one or more heteroatoms selected from N, O or S;R.sup.9 is H or C.sub.1-4 alkyl;R.sup.10 and R.sup.11 are independently selected from H and C.sub.1-4 alkyl;are useful in the treatment of hypertension, myocardial infarction, male erectile dysfunction (MED), hyperlipidaemia, cardiac arrhythmia, glaucoma and benign prostatic hyperplasia (BPH). They also find utility in the treatment of female sexual arousal dysfunction (FSAD). Excerpt(s): This invention relates to novel compounds useful in therapy. It also relates to compositions containing such derivatives and to their use. They have potential utility in the treatment of hypertension, myocardial infarction, male erectile dysfunction (MED), hyperlipidaemia, cardiac arrhythmia, glaucoma and benign prostatic hyperplasia (BPH). They also may be useful in the treatment of female sexual arousal dysfunction (FSAD). International Patent Application WO 97/23462 discloses quinoline and quinazoline compounds having a 5-phenyl substituent. The compounds are indicated in the treatment of benign prostatic hyperplasia. International Patent application WO 98/30560 discloses quinoline and quinazoline compounds indicated in the treatment of benign prostatic hyperplasia. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Cyanophenyl derivative Inventor(s): Hirano, Masaaki; (Ibaraki, JP), Imamura, Masakazu; (Ibaraki, JP), Kamikubo, Takashi; (Ibaraki, JP), Kawaminami, Eiji; (Ibaraki, JP), Kinoyama, Isao; (Ibaraki, JP), Koutoku, Hiroshi; (Ibaraki, JP), Matsuhisa, Akira; (Ibaraki, JP), Miyazaki, Yoji; (Ibaraki, JP), Moritomo, Hiroyuki; (Ibaraki, JP), Nozawa, Eisuke; (Ibaraki, JP), Ohta, Mitsuaki; (Ibaraki, JP), Okada, Minoru; (Ibaraki, JP), Samizu, Kiyohiro; (Ibaraki, JP), Taniguchi, Nobuaki; (Ibaraki, JP), Toyoshima, Akira; (Ibaraki, JP) Correspondence: Sughrue Mion, Pllc; 2100 Pennsylvania Avenue, N.W.; Washington; DC; 20037; US Patent Application Number: 20040010037 Date filed: June 30, 2003 Abstract: This application relates to a piperazino-substituted novel cyanophenyl derivative in which a substituted carbamoyl or substituted sulfamoyl group having an aryl, heterocyclic or the like group that may have a substituent group is bonded to one nitrogen atom on the piperazine ring. The compound of this application has an antiandrogen action and is useful in preventing or treating prostatic cancer, benign prostatic hyperplasia and the like diseases. Excerpt(s): This is a divisional of application Ser. No. 09/787,672 filed Mar. 21, 2001, which is a Continuation Application of PCT Application No. PCT/JP99/05149 filed Sep. 21, 1999; the above noted prior applications are all hereby incorporated by reference. This invention relates to novel cyanophenyl derivatives useful as medicaments, particularly as an anti-androgen, and salts and pharmaceutical compositions thereof. Androgen as a steroid hormone is secreted from testis and adrenal cortex and induces male sex hormone actions. Androgen, when incorporated into target cells, acts upon an androgen receptor and the receptor to which androgen binds forms a dimer. Subsequently, this dimer binds to an androgen-response-element on DNA to accelerate synthesis of mRNA and to thereby induce proteins which control the androgen actions, thus expressing various actions within living organism (Prostate Suppl., 6, 1996, 45-51, Trends in Endocrinology and Metabolism, 1998, 9 (8), 317-324). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Gleason grade 4/5 prostate cancer genes Inventor(s): Warrington, Janet A.; (Los Altos, CA) Correspondence: Alison B. Mohr; Parsons Behle & Latimer; Suite 1800; 201 South Main Street; Salt Lake City; UT; 84111-2218; US Patent Application Number: 20030113762 Date filed: August 16, 2002 Abstract: Sixty-four down regulated and 22 up regulated genes have been indentified in Gleason grade 4/5 cancer, using the gene profile from benign prostatic hyperplasia as control tissue. Hepsin appears to be the most promising of the up regulated genes. PSMA is also highly overexpressed at the transcript level in grade 4/5 cancer, reemphasizing its potential importance as a target for chemotherapy. The regulated genes can be used diagnostically, prognostically, and therapeutically. They can be used to form prostate specific expression monitoring tools.

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Excerpt(s): This application claims priority to Provisional Application Serial No. 60/312,745 filed Aug. 17, 2001, which is herein incorporated by reference in its entirety for all purposes. The invention relates to the field of cancer diagnostics and therapeutics. In particular it relates to prostate cancer. Prostate cancer, along with lung and colon cancer, are the three most common causes of death from cancer in men in the United States. Greenlee, R. T., Hill-Hannon, M. B., Murray, T., Thun, M., Cancer Statistics, 2001, CA Cancer J Clin, 15, 2001, which is herein incorporated by reference in its entirety. However, prostate cancer is by far the most prevalent of all human malignancies with the exception of skin cancer. Scott, R., Mutchnik, D. L., Laskowski, T. Z., Schmalhorst, W. R., Carcinoma of the prostate in elderly men: Incidence, growth characteristics and clinical significance, J Urol, 101: 602-607,1969 and Sakr, W. A., Haas, G. P., Cassin, B. F., Pontes, J. E., Crissman, J. D., The frequency of carcinoma and intraepithelial neoplasia of the prostate in young male patients, J Urol, 150: 379-385,1993, which are herein incorporated by reference in their entirety. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Identifying drugs for and diagnosis of benign prostatic hyperplasia using gene expression profiles Inventor(s): Getzenberg, Robert H.; (Pittsburgh, PA), Kulkarni, Prakash; (Gaithersburg, MD), Munger, William E.; (Gaithersburg, MD), Waga, Iwao; (Yokohama, JP), Yamamoto, Jun; (Yokohama, JP) Correspondence: Morgan Lewis & Bockius Llp; 1111 Pennsylvania Avenue NW; Washington; DC; 20004; US Patent Application Number: 20030134280 Date filed: September 24, 2001 Abstract: The present invention is based on the elucidation of the global changes in gene expression in prostate tissue isolated from patients exhibiting different clinical states of prostate hyperplasia as compared to normal prostate tissue as well as the identification of individual genes that are differentially expressed in diseased prostate tissue. Excerpt(s): This application claims priority of U.S. Provisional Application No. 60/223,323, filed Aug. 7, 2000, and U.S. application Ser. No. 09/873,319, filed Jun. 5, 2001, which are herein incorporated by reference in their entirety. Benign Prostatic Hyperplasia (BPH) is the most common benign tumor in men aged >60 years. It is estimated that one in four men living to the age of 80 will require treatment for this disease. BPH is usually noted clinically after the age of 50, the incidence increasing with age, but as many as two thirds of men between the ages of 40 and 49 demonstrate histological evidence of the disease. The anatomic location of the prostate at the bladder neck enveloping the urethra plays an important role in the pathology of BPH, including bladder outlet obstruction. Two prostate components are thought to play a role in bladder outlet obstruction. The first is the relative increased prostate tissue mass. The second component is the prostatic smooth muscle tone. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Immunological test and diagnostic kit for prostate adenocarcinoma Inventor(s): Charrier, Jean-Philippe; (Ecully, FR) Correspondence: James C Lydon; Suite 100; 100 Daingerfield Road; Alexandria; VA; 22314; US Patent Application Number: 20040038321 Date filed: December 12, 2002 Abstract: This invention concerns a test method for the purposes of diagnosis, prognosis or therapeutic monitoring in male patients with adenocarcinoma of the prostate or benign prostatic hyperplasia, which does not require a biopsy of prostate tissue, and which exploits the combination of at least one tissue-specific marker and at least one marker for inflammation in order to arrive at a diagnosis.The invention also concerns a process using such a method, an immunological test to implement such a process, and a diagnostic kit.The invention is applied to the diagnosis of adenocarcinoma of the prostate and benign prostatic hyperplasia. Excerpt(s): This invention concerns a screening or diagnostic method for the detection of prostate cancer (i.e. adenocarcinoma of the prostate, usually abbreviated to PCa) and benign prostatic hyperplasia (abbreviated to BPH) in patients, a method which does not involve the taking of a biopsy. More generally, the invention concerns a test method for the purposes of diagnosis, prognosis or therapeutic monitoring of cancer in human patients. By diagnosis, it is meant that the marker reveals whether or not the patient is suffering from a certain disease. By prognosis, it is meant that the marker reveals the seriousness of the disease. The prognosis can guide the therapeutic strategy. Finally, by therapeutic monitoring, it is meant that the marker can be used to follow the efficacy of treatment. If the chosen treatment strategy is failing (as revealed by the marker), the patient can be offered an alternative. Prostate-specific antigen (PSA) is synthesized by epithelial cells of the human prostate gland, probably in the form of an inactive zymogen (Lundwall et al. FEBS LeH 1987) and is secreted in the seminal fluid in an active form (Lilja, J. Clin Invest 1985). The biological activity of PSA in seminal fluid consists of controlled proteolysis of the most abundant proteins secreted by the seminal vesicles (Lilja, J. Clin Invest 1985; Lilja et al. J. Clin Invest 1987; Mc Gee et al. Biol. Reprod. 1988). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Insulin-like growth factor system and cancer Inventor(s): Diamandi, Anastasia; (Toronto, CA), Khosravi, M. Javad; (Toronto, CA), Mistry, Jehangir; (League City, TX) Correspondence: Haynes And Boone, Llp; 901 Main Street, Suite 3100; Dallas; TX; 75202; US Patent Application Number: 20030017513 Date filed: March 7, 2002 Abstract: Method of monitoring or diagnosing disease conditions, including disease of the prostrate, that involve measuring a combination of tumour markers and at least one component of the IGF axis. The invention is exemplified with prostate cancer and benign prostatic hyperplasia, the tumor marker prostate specific antigen, and the insulin-like growth factors and their binding proteins.

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Excerpt(s): This invention relates to the measurement of the IGF-axis component levels and tumor marker levels for use in assessing cancer risk and/or progression and/or distinguishing between cancer and other non-malignant disorders. The invention is exemplified with prostate cancer (CaP) and benign prostatic hyperplasia (BHP), the tumor marker prostate specific antigen (PSA), and the insulin-like growth factors (IGF) and their binding proteins (IGFBP). Specifically, IGF-I, intact IGFBP-3, fragment IGFBP3, total IGFBP-3, free PSA and total PSA were assayed and certain permutations of these measurements were found to present improved diagnostic indicators. The method is predicted to have general applicability to other IGF-system related cancers. The insulinlike growth factor (IGF) family of high affinity IGF binding proteins (IGFBP-1-6) (14) has recently evolved to a superfamily status in order to accommodate a related group of newly discovered low affinity IGFBPs called the IGFBP related proteins (5). The conventional view of IGFBPs as the sole regulators of IGF bioavailability and bioactivity has also evolved to include the IGF-independent properties of IGFBPs (6, 7). IGFBPs, particularly IGFBP-3, have been recently identified as potent apoptotic agents (8-12), presumably mediating the effects of cellular growth suppressing mechanisms (8, 11, 12). The emerging new concept appears to similarly broaden the pathophysiological roles of the IGF peptides to include their potential involvement in regulation of the IGFBPs' bioactivity (8). In this ever-expanding maze of reciprocal molecular interactions, posttranslational modification by selective proteolysis is rapidly gaining acceptance as the key modulator of the IGF/IGFBP system and a major determinant of their effects on cellular growth and metabolism (13, 14). Insulin-like growth factors (IGF-I and -II) are mitogenic and anti-apoptotic agents produced primarily by the liver and locally by a wide variety of tissues. IGFs circulate mostly complexed with IGFBP-3, which in association with the acid-labile subunit (ALS) forms an approximately 150 kD ternary protein complex (1-4). Under normal conditions, nearly all of the circulating IGFs remain ternary complexed (75-80%), and smaller proportions (20-25%) are associated with the low molecular weight IGFBPs (IGFBP-1, IGFBP-2, IGFBP-4, IGFBP-5, and IGFBP-6) or exist in the free form (1-4). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Methods and compositions for inhibiting the proliferation of prostate cancer cells Inventor(s): Xing, Niazeng; (US), Young, Charles; (Rochester, MN) Correspondence: Fish & Richardson P.C.; 3300 Dain Rascher Plaza; 60 South Sixth Street; Minneapolis; MN; 55402; US Patent Application Number: 20030054053 Date filed: September 20, 2001 Abstract: The invention provides for methods of monitoring the proliferation of cultured prostate cancer cells in the presence of silymarin, methods of treating an individual with prostate cancer or at risk of developing prostate cancer, and methods of reducing the risk of recurrence of prostate cancer in an individual who had previously been treated for prostate cancer. Methods of the invention further include treating an individual with benign prostatic hyperplasia (BPH) with silymarin as well as methods of screening for compounds that inhibit the proliferation of prostate cancer cells. The invention provides for compositions and articles of manufacture containing silymarin in particular formulations, and silymarin with a second compound that also exerts an effect on the androgen receptor.

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Excerpt(s): This invention relates to prostate cancer, and more particularly to methods and compositions for inhibiting the proliferation of prostate cancer cells. The prostate gland is located between the bladder and the rectum and wraps around the urethra. The prostate is composed of glandular tissue that produces a milky fluid and smooth muscles that contract during sex and squeeze this fluid into the urethra where it mixes with other fluid and sperm to form semen. The prostate gland converts testosterone to a more powerful male hormone, dihydrotestosterone, which affects the size of the gland and plays an important role in prostate cancer. Prostate cancer is a malignant tumor that arises in the prostate gland and can eventually spread through the blood and lymph fluid to other organs, bones, and tissues. Prostate cancer is the most commonly diagnosed cancer in the U.S., and it is the second leading cause of cancer death in American men after non-melanoma skin cancer. Although prostate cancer is just as common in Japan as in the United States, death rates from prostate cancer are significantly lower in Japan. It is unlikely that these differences are all genetic, because Japanese men who migrate to the United States die of prostate cancer with increasing frequency as a function of the number of years they reside in the United States. It is possible that this paradox could be explained, at least in part, by dietary factors. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Methods and compositions for the treatment of benign prostatic hypertrophy Inventor(s): Randhava, Sarabjit; (Evanston, IL), Randhava, Sikander; (Evanston, IL), Randhava, Surjit; (Evanston, IL) Correspondence: Katten Muchin Zavis Rosenman; Attention: Patent Administrator; Suite 1600; 525 West Monroe Street; Chicago; IL; 60661-3693; US Patent Application Number: 20030096009 Date filed: October 23, 2002 Abstract: This invention relates to a composition for use in treating benign prostatic hyperplasia including a saw palmetto extract provided in an oral controlled release formulation which allows release of active ingredients in the intestinal tract and which allows the maintenance of therapeutic levels of active agents in the bloodstream for prolonged periods of time. This invention also relates to a composition for improving the efficacy of a saw palmetto extract, a method of treating benign prostatic hypertrophy, and a method of improving the efficacy of a saw palmetto extract treatment. Excerpt(s): This invention relates to a composition for use in treating benign prostatic hyperplasia, which comprises saw palmetto extract contained in a controlled delivery system. The composition is preferably administered orally, uses a controlled delivery system to provide a targeted, extended release of the saw palmetto extract into the bloodstream. Many men over the age of fifty commonly experience a condition known as benign prostatic hyperplasia, or BPH. BPH affects as much as 40% of the male population over the age of seventy. The condition is commonly recognized as a swelling of the prostate gland. This problem gradually manifests itself in the form of a) frequent urination, b) small discharge volumes and "dribbling", and c) unsatisfying bladder evacuations. Waking up to urinate once or more each night is a typical sign of this problem. BPH is a chronic condition that tends to gradually worsen with age. The increased incidence of BPH in older men may be due to the fact that as men age, testosterone levels tend to decline and estrogen levels rise. In the process, testosterone metabolism takes a different pathway, and testosterone is converted to

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dihydrotestosterone (DHT), a potent male hormone that causes prostate enlargement. The actions of DHT can be limited by restricting the enzymatic production of DHT from testosterone and/or blocking the direct pharmacological action of DHT at the receptor level. Current therapies for BPH focus on limiting the actions of DHT, and include: pharmaceutical intervention with 5-.alpha.-reductase inhibitors such as finasteride (Proscar.RTM.); pharmacological intervention with.alpha.-adrenergic blockers, such as terazosin HCl (Hytrin.RTM.), and doxazosin mesylate (Cardura.RTM.); prostatectomy; and administration of saw palmetto extract. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Novel antibody, immunoassay and method for prostate cancer detection Inventor(s): Lilja, Hans; (Skanor, SE), Lovgren, Timo; (Turku, FI), Niemela, Pauliina; (Turku, FI), Pettersson, Kim; (Turku, FI) Correspondence: Rothwell, Figg, Ernst & Manbeck, P.C.; 1425 K Street, N.W.; Suite 800; Washington; DC; 20005; US Patent Application Number: 20040101914 Date filed: July 21, 2003 Abstract: This invention concerns an antibody wherein said antibody does bind with high affinity to human single-chain intact, i.e. not internally cleaved, mature and/or zymogen forms of prostate specific antigen (SCINT PSA). The antibody, obtainable through immunization with an uncleaved form of PSA and selected by its differential reactivity with the intact and internally cleaved forms, does not bind to a nicked PSA (PSA-N), wherein said PSA-N has been formed by internal peptide bond cleavage(s) of SCINT PSA resulting in two-chain or multi-chain PSA. This invention further concerns an immunoassay and a method for differentiating patients with cancer of the prostate (PCa) from patients with benign prostatic hyperplasia (BPH) and/or healthy male subjects without PCa, patients with aggressive PCa from patients with indolent PCa and/or patients with clinically localized and/or organ confined PCa from patients with extraprostatic extension of PCa and/or PCa with metastatic spread to lymph nodes or bone marrow using said antibody. Excerpt(s): This invention relates to high affinity immunoreagents which are specific for the single-chain, intact (i.e. not internally-cleaved) form(s) of prostate specific antigen (PSA or hK3). It also relates to the discrimination of prostate cancer from healthy asymptomatic men or benign prostatic conditions by an analytically sensitive immunoassay, employing the aforementioned immunoreagents, for the specific determination of the single-chain, intact (not internally cleaved) form(s) of free, noncomplexed PSA (free SCINT PSA), or by combining the result from this immunoassay with immunoassays measuring any other forms of the prostatic kallikreins, PSA or hK2, either by forming various ratios of these or by combining them with other means, e.g. using logistic regression and/or artificial neural networks. The invention may be used for detection of prostate cancer both in screening of asymptomatic individuals as well as in distinguishing cancer from benign conditions in men presenting with clinical symptoms (e.g. lower urinary tract symptoms, LUTS). Further, the invention may be used to improve the staging and grading of prostate cancer as well as to provide improved means to detect recurrency of cancer at early stage and provide improved means to monitor therapeutic response at various stages of disease. Suitable biological specimens for the immunoassay determinations are mainly serum, plasma or whole blood samples, but the invention may also be applied to other

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biological fluids such as urine and seminal fluid samples. The publications and other materials used herein to illuminate the background of the invention, and in particular, cases to provide additional details respecting the practice, are incorporated by reference. Prostate-specific antigen (PSA; also designated hK3) and human glandular kallikrein 2 (hK2) are two closely related serine proteases highly expressed, predominantly in prostatic tissue. [Wang et al. Invest Urol 1979; 17:159-163, Lilja J Clin Invest 1985; 76:1899-1903, Chapdelaine et al. FEBS Lett 1988; 236:205-208]. The PSA gene is located on the long arm of chromosome 19 and has >84% nucleotide sequence identity with hK2. The two proteins also show extensive similarity in amino-acid sequence (79%) but the expression rates are quite different (hK2 mRNA levels amount to.about.10-20% of PSA mRNA levels) [Schedlich et al. DNA 1987; 6:429-437]. PSA is synthesized as a 261 amino acid preproform from which the 17-21 amino acid signal peptide is cleaved and released in the secretion process. The remaining zymogen form of PSA is activated to an active serine protease by cleavage of 3-7 amino acid propeptide [Lovgren et al Biochem. Biophys. Res. Comm. 1997; 238; 549-555]. Recently, recombinant hK2 was shown to convert in vitro inactive recombinant proPSA into active mature PSA [Lovgren et al. Biochem Biophys Res Commun 1997; 238:549-555, Takayama et al. J Biol Chem 1997; 272:21582-21588, Kumar et al. Cancer Res 1997; 57:3111-3114]. Therefore, hK2 is likely a physiological activator of proPSA. Enzymatically active PSA is secreted into seminal fluid at high concentrations (0.2-5 mg/mL) [Christensson et al. Eur J Biochem 1990; 194:755-763, Ahlgren et al. 1995 J Androl 16:491-498]. In semen, PSA degrades the seminal vesicle derived gel-forming proteins semenogelin I and II, causing liquefaction of semen and release of progressively motile spermatozoa [Lilja J Clin Invest 1985; 76:1899-1903]. The action of PSA generates hydrolysis of peptide bonds, mainly Cterminal, of certain tyrosine- and glutamine residues in semenogelin I and II [Malm et al. The Prostate 2000; In press]. By contrast, hK2 generates distinctly different cleavage patterns in semenogelin I and II compared to those generated by the action of PSA, though it is presently unclear whether the hK2 action on the gel proteins has physiological significance [Lovgren et al. Eur. J. Biochem. 1999; 262; 781-789]. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Novel forms of prostate specific antigen (PSA) specific for benign prostatic hyperplasia (BPH) and methods of using such Inventor(s): Mikolajczyk, Stephen D.; (San Diego, CA), Rittenhouse, Harry G.; (Del Mar, CA), Slawin, Kevin; (Houston, TX), Wang, Tang Jang; (Poway, CA), Wolfert, Robert L.; (San Diego, CA) Correspondence: Hogan & Hartson L.L.P.; 500 S. Grand Avenue; Suite 1900; Los Angeles; CA; 90071-2611; US Patent Application Number: 20030119033 Date filed: September 24, 2002 Abstract: A substantially pure and isolated novel form of prostate specific antigen (PSA) is provided. The novel form of PSA of the present invention comprises at least one clip at Lys 182 of the amino acid sequence of a mature form of PSA. Preferably, the novel form of PSA additionally comprises one or more clips at a location selected from a group consisting of Ile 1, Lys 145, and Lys 146. More preferably, the form of PSA contains at least two clips at Lys 145 and Lys 182 of the amino acid sequence of a mature form of PSA. The novel forms of PSA exist at an elevated level in patients suspected of having benign prostatic hyperplasia (BPH) and therefore may be used as a serum mark or an immunohistological marker to help distinguish BPH from prostate cancer. Antibodies recognizing the novel forms of PSA and immunoassays that detect and

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determine the novel forms of PSA of the present invention in a sample are also provided. Further provided are a kit and a method for detecting the novel forms of PSA for aiding in the differentiation of prostate cancer from BPH. Excerpt(s): The invention relates generally to prostate specific antigen (PSA) and specifically to new forms of PSA that are specific for benign prostatic hyperplasia and methods of using the new forms of PSA. Throughout this application, various references are referred to within parentheses. Disclosures of these publications in their entireties are hereby incorporated by reference into this application to more fully describe the state of the art to which this invention pertains. Full bibliographic citation for these references may be found at the end of this application, preceding the claims. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Pharmaceutical combination for the treatment of benign prostatic hyperplasia or for the long-term prevention of acute urinary retention Inventor(s): Baiker, Wolfgang; (Volxheim, DE), Mehlburger, Ludwig; (Bingen/Rhein, DE) Correspondence: Boehringer Ingelheim Corporation; 900 Ridgebury Road; P. O. Box 368; Ridgefield; CT; 06877; US Patent Application Number: 20030225118 Date filed: April 24, 2003 Abstract: The present invention relates to a new pharmaceutical combination for treating benign prostatic hyperplasia (BPH) or for the long-term prevention of acute urinary retention (AUR). Excerpt(s): The present invention relates to a pharmaceutical combination suitable for the treatment of benign prostatic hyperplasia or for the long-term prevention of acute urinary retention. BPH, a benign, non-cancerous enlargement of the prostate, is a wellknown complaint in men, which generally comes to medical attention from the age of 50 onwards. About 50% of all men aged over 50 and 95% of all men aged over 70 are affected by it. BPH is a generally progressive condition which in serious cases may endanger kidney function and require surgical intervention. The number of untreated patients runs at over 37 million worldwide. The reduced flow rate and voiding (obstructive) symptoms of BPH are generally considered to be caused by two main factors, the enlarged prostatic gland (the static component), and the tone of the smooth muscle of the stroma and urethra (the dynamic component). Storage (irritative) symptoms have been associated with bladder dysfunction secondary to outflow obstruction. The growth and tone of the prostate compresses or lengthens the urethra, causing the symptoms of urethral blockage and possibly leading to urinary retention. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Protease and an aminopeptidase associated with development of benign prostatic hyperplasia (BPH) Inventor(s): Mikolajczyk, Stephen D.; (San Diego, CA), Rittenhouse, Harry G.; (Del Mar, CA) Correspondence: Wei- Ning Yang; Hogan & Hartson L.L.P.; 500 South Grand Avenue; Suite 1900; Los Angeles; CA; 90071; US Patent Application Number: 20030166036 Date filed: May 18, 2001 Abstract: Methods for identification and isolation of a benign prostate specific antigen (BPSA) protease and BPSA aminopeptidase are provided. The BPSA protease of the present invention preferentially cleaves prostate specific antigen (PSA) at residue Lys182 and does not react with the residue Arg85. The BPSA aminopeptidase cleaves BPSA between residues Ile1 and Val2 and between residues Lys146 and Leu147, but does not cleave BPSA at Ser183. Excerpt(s): The invention relates to proteases and aminopeptidases, and specifically to a protease and an aminopeptidase associated with the formation of hyperplastic prostate tissues, and the development of BPH nodules and methods of identification, isolation and use of the protease and the aminopeptidase. The invention is also related to inhibitors of the protease, and the aminopeptidase and the use of such inhibitors. Throughout this application, various references are referred to within parentheses. Disclosures of these publications in their entireties are hereby incorporated by reference into this application to more fully describe the state of the art to which this invention pertains. Full bibliographic citations for these references may be found at the end of this application, preceding the claims. Adenocarcinoma of the prostate accounts for a significant number of malignancies in men over 50. Currently used screening methods measure the serum level of prostate specific antigen (PSA) as a marker for the presence of prostate cancer (1-3). PSA is a 33 kD glycoprotein synthesized in the epithelial cells of the prostate gland. It is a secreted serine protease of the kallikrein family (extensively reviewed in (4)). The mature form of PSA has isoleucine as the N-terminal and 237 amino acid residues with a molecular mass of 28,400 D (5,6). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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PSP94 diagnostic reagents and assays Inventor(s): Panchal, Chandra J.; (London, CA), Reeves, Jonathan; (Hawkesbury, CA), Tanner, Jerome Edward; (Dollard-des-Ormeaux, CA) Correspondence: Ronald S. Kosie; Brouillette Kosie Prince; 25th Floor; 1100 ReneLevesque Boulevard West; Montreal; QC; H3b 5c9; CA Patent Application Number: 20040009164 Date filed: May 1, 2003 Abstract: In the serum, PSP94 occurs as a free form or is associated with a carrier protein. PSP94 in its bound form has been quantified in the blood of prostate cancer patients and these measurements have shown utility as evaluation of prognosis. The present invention identifies a carrier protein to which PSP94 is bound (named PSP94binding protein) its purification process, its nucleic acid and amino acid sequence and to the use of these sequences in the diagnosis and prognosis of PSP94 related disease. More

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particularly, the present invention discloses improved diagnostic and prognostic assays as well as reagents useful for the evaluation of conditions linked with abnormal or elevated levels of PSP94, such as prostate cancer and benign prostatic hyperplasia. Excerpt(s): This invention relates to new polypeptides able to bind PSP94 (PSP94binding protein), as well as nucleic acid and amino acid sequences, and the use of these sequences in the diagnosis and prognosis of diseases. This invention also relates to improved diagnostic assays, kit and reagents such as antibodies able to recognize PSP94 or a PSP94-binding protein. The prostate gland, which is found exclusively in male mammals, produces several components of semen and blood and several regulatory peptides. The prostate gland comprises stromal and epithelial cells, the latter group consisting of columnar secretory cells and basal nonsecretory cells. A proliferation of these basal cells as well as stromal cells gives rise to benign prostatic hyperplasia (BPH), which is one common prostate disease. Another common prostate disease is prostatic adenocarcinoma (CaP), which is the most common of the fatal pathophysiological prostate cancers, and involves a malignant transformation of epithelial cells in the peripheral region of the prostate gland. Prostatic adenocarcinoma and benign prostatic hyperplasia are two common prostate diseases, which have a high rate of incidence in the aging human male population. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Regimen for treating prostate tissue and surgical kit for use in the regimen Inventor(s): Escandon, M. Alejandro Sousa; (Lugo, ES), Neisz, Johann J.; (Minnetonka, MN) Correspondence: Faegre & Benson Llp; 2200 Wells Fargo Center; 90 South Seventh Street; Minneapolis; MN; 55402-3901; US Patent Application Number: 20030092689 Date filed: July 9, 2002 Abstract: The present invention provides treatment regimens for treating diseased prostate tissue, including the steps of chemically ablating prostate tissue and coadministering an antiandrogen. In some embodiments, prostate tissue is chemically ablated by injection of ethanol, or an injectable gel comprising ethanol, into prostate tissue. Steroidal and non-steroidal antiandrogens are suitable antiandrogens. One suitable non-steroidal antiandrogen is bicalutamide. The treatment regimen is suitable for treatment of prostate tissue diseases including benign prostatic hyperplasia and prostatic carcinoma. The invention further provides a treatment regimen for treating benign prostatic hyperplasia, including the steps of damaging prostate tissue and coadministering an antiandrogen. Also provided by the present invention is a kit for treating a human male, including a means for necrosing prostate tissue, an antiandrogen drug, and a means for administering the antiandrogen drug. A kit including a first surgical device for delivering a chemoablation fluid to prostate tissue transurethrally, an antiandrogen drug such as bicalutamide, and a second surgical device for administering the antiandrogen drug, is further provided. Excerpt(s): This application claims priority to U.S. Provisional Application No. 60/304,149 filed Jul. 10, 2001 and entitled "Method of Treating Prostate Tissue and Surgical Kit for Use in the Method," the entire disclosure of which is hereby incorporated by reference. This application also claims priority to U.S. Provisional Application No. 60/329,262 filed Oct. 12, 2001 and entitled "Surgical Instrument and

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Method," the entire disclosure of which is hereby incorporated by reference. The present invention relates to treatment regimens for treating diseased prostate tissue, and to surgical kits for use in a treatment regimen. Prostate disease is a significant health risk for males. Diseases of the prostate include prostatitis, benign prostatic hyperplasia (BPH, also known as benign prostatic hypertrophy), and prostatic carcinoma. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Regulation of human adenylate cyclase Inventor(s): Zhu, Zhimin; (Waban, MA) Correspondence: Banner & Witcoff; 1001 G Street N W; Suite 1100; Washington; DC; 20001; US Patent Application Number: 20040063174 Date filed: October 14, 2003 Abstract: Reagents which regulate human adenylate cyclase and reagents which bind to human adenylate cyclase gene products can play a role in preventing, ameliorating, or correcting dysfunctions or diseases including, but not limited to, peripheral and central nervous system disorders, disorders of the genito-urinary system including but not limited to benign prostatic hyperplasia and urinary incontinence, obesity, COPD and diabetes. Excerpt(s): This application incorporates by reference U.S. provisional applications Serial No. 60/247,005 filed Nov. 13, 2000 and U.S. 60/267,181 filed Feb. 8, 2001. The invention relates to a novel human adenylate cyclase and its regulation for therapeutic uses. Cyclases play important roles in the transduction of extracellular signals via their synthesis of "secondary messengers" such as adenosine 3',5'-cyclic phosphate (cyclic adenosine monophosphate, cAMP) and guanosine 3',5'-cyclic phosphate (cyclic guanosine monophosphate, cGMP). Cell surface receptors mediate the transduction of an extracellular signal, such as the binding of a ligand to a receptor, into a signal that is transmitted internally within the cell. The internal signal is carried by secondary messengers, which typically are produced in response to the binding of an external signal. The secondary messengers in turn activate particular proteins and other regulators within the cell which have the potential to regulate expression of specific genes or to alter a metabolic process. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Remedies for vesical stimulation association with prostatauxe Inventor(s): Atsuki, Kaoru; (Sunto-gun, JP), Karasawa, Akira; (Sunto-gun, JP), Ohno, Tetsuji; (Sunto-gun, JP), Sirakura, Shiro; (Mishima-shi, JP), Yamagata, Tsuyoshi; (Suntogun, JP) Correspondence: Fitzpatrick Cella Harper & Scinto; 30 Rockefeller Plaza; New York; NY; 10112; US Patent Application Number: 20040110784 Date filed: September 22, 2003 Abstract: The present invention provides a therapeutic agent for bladder irritative symptoms associated with benign prostatic hyperplasia comprising, as an active

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ingredient, a tricyclic compound represented by formula (I): 1[wherein R.sup.1 represents a hydrogen atom, substituted or unsubstituted lower alkyl, substituted or unsubstituted lower alkoxy or halogen;X.sup.1--X.sup.2--X.sup.3 represents CR.sup.5.dbd.CR.sup.6-CR.sup.7.dbd.CR-.sup.8, N(O).sub.m.dbd.CR.sup.6CR.sup.7.dbd.CR.sup.8, CR.sup.5.dbd.CR.sup.6--N(O).sub.m.dbd.CR.sup.8, CR.sup.5.dbd.CR.sup.6-CR.sup.7.dbd.N(O).sub.m, CR.sup.5.dbd.CR.sup.6--O, CR.sup.5.dbd.CR.sup.6--S, O--CR.sup.7.dbd.CR.sup.8, S--CR.sup.7.dbd.CR.sup.8 or O-CR.sup.7.dbd.N;Y represents 13 CH.sub.2S--, --CH.sub.2SO--, --CH.sub.2SO.sub.2--, -CH.sub.2O--, --CH.dbd.CH--, --(CH.sub.2).sub.p--, --SCH.sub.2--, --SOCH.sub.2--, -SO.sub.2CH.sub.2-- or --OCH.sub.2-; and R.sup.2 represents a hydrogen atom, substituted or unsubstituted lower alkyl, substituted or unsubstituted lower alkenyl, substituted or unsubstituted lower alkoxy, amino, mono(substituted or unsubstituted lower alkyl)-substituted amino, di(substituted or unsubstituted lower alkyl)-substituted amino, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted aralkylamino, substituted or unsubstituted arylamino or a substituted or unsubstituted heteroalicyclic group] or a pharmaceutically acceptable salt thereof. Excerpt(s): The present invention relates to a therapeutic agent for bladder irritative symptoms associated with benign prostatic hyperplasia. Benign prostatic hyperplasia is benign adenoma generated in a transitional zone of the prostate that wraps the urethra. Patients with benign prostatic hyperplasia complain of bladder outlet obstructive symptoms or bladder irritative symptoms. Examples of bladder outlet obstructive symptoms include a hesitation before urine flow starts, straining, a weak urinary stream, an intermittent urinary stream, dribbling at the end of urination, prolongation of urination and overflow incontinence. Examples of bladder irritative symptoms include urinary frequency at daytime, urinary frequency at night, urinary urgency, a feeling of incomplete emptying and a reduced voided volume per micturition. Functional obstruction and mechanical obstruction are involved in the development of these urinary disturbances due to benign prostatic hyperplasia. Further, these functional and mechanical obstructions cause secondary changes in detrusor muscle or nerves, which induce the complicated pathological phenomena such as bladder irritative symptoms and bladder outlet obstructive symptoms. At present, for examples,.alpha.sub.1-receptor blockers, anti-androgen agents, plant preparations, amino acid preparations, or the like are used as a therapeutic agent for benign prostatic hyperplasia. Among these, examples of the.alpha.sub.1-receptor blockers include tamsulosin hydrochloride, prazosin hydrochloride, terazosin hydrochloride and urapidil. Examples of the antiandrogen agents include chlormadinone acetate, allylestrenol, gestonorone caproate, oxendolone and finasteride. The.alpha.sub.1-receptor blockers inhibit the functional urethral obstruction, that is, contractions of prostatic smooth muscle induced by noradrenaline, secreted by stimulation of the sympathetic nerve, via the.alpha.sub.1receptor. The anti-androgen agents inhibit the mechanical obstruction, that is, a rise in urethral resistance resulting from the pressure caused by the enlarged prostate itself. However, although the.alpha.sub.1-receptor blockers and anti-androgen agents are recognized to be effective for bladder outlet obstructive symptoms of benign prostatic hyperplasia, their effects on improvement of bladder irritative symptoms are insufficient. The plant preparations and amino acid preparations, which have antiinflammatory activity, anti-edema activity, or the like, improve the bladder irritative symptoms by alleviating the outflow obstruction at the bladder neck; but their effects are weak and the dose required is large so that they are a burden to aged people. Under these circumstances, there exists a need for a therapeutic agent to alleviate bladder irritative symptoms.

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Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Use of alpha1-adrenoreceptor antagonists in the prevention and treatment of benign prostatic hyperplasia Inventor(s): Thompson, Timothy C.; (Houston, TX), Wyllie, Michael G.; (New York, NY), Yang, Guang; (Houston, TX) Correspondence: Pfizer Inc; 150 East 42nd Street; 5th Floor - Stop 49; New York; NY; 10017-5612; US Patent Application Number: 20030125335 Date filed: February 18, 2003 Abstract: A method for treating or preventing a BPH in a mammal which comprises administering to said mammal an amount of a drug, comprising an.alpha.sub.1adrenoreceptor antagonist or pharmaceutically acceptable acid addition salt thereof, effective for treating or preventing the BPH. Excerpt(s): This invention relates to the use of.alpha.sub.1-adrenoreceptor antagonists, or pharmaceutically acceptable acid addition salts, thereof for treating or preventing the formation of benign prostatic hyperplasia (BPH) in mammals. More particularly, it relates to a method for preventing the formation of, or reducing, BPH in mammals by administering to said mammals an.alpha.sub.1-adrenoreceptor antagonist or pharmaceutically acceptable acid addition salt thereof. Benign prostatic hyperplasia (BPH) is one of the most common, nonmalignant neoplastic processes to affect the aging man. Symptoms occur in about 50 and up to 80% of men 60 years old and older than 80 years, respectively. In the United States BPH is an important health problem resulting in an estimated 1.7 million visits to physicians offices each year. BPH results from a progressive enlargement of the prostate, leading to urethral constriction, a disturbance in normal urinary outfow, urinary retention and associated irritative symptoms. In symptomatic BPH there appear to be two components of the urethral obstruction: a static component related to prostatic mass and a dynamic component related to the noradrenergic tone in the prostatic and urethral smooth muscle. A number of functional studies have shown that the contractile response is primarily mediated by.alpha.sub.1adrenoreceptors. Autoradiographical data suggest that these are primarily located on stromal smooth muscle. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Use of inhibitors of the EGFR-mediated signal transduction for the treatment of benign prostatic hyperplasia (BPH)/prostatic hypertrophy Inventor(s): Colbatzky, Florian; (Stafflangen, DE), Platz, Stefan; (Ummendorf, DE), Singer, Thomas; (Inzlingen, DE) Correspondence: Boehringer Ingelheim Corporation; 900 Ridgebury Road; P. O. Box 368; Ridgefield; CT; 06877; US Patent Application Number: 20030225079 Date filed: May 8, 2003 Abstract: The present invention relates to the use of specific EGF-receptor antagonists for preparing a pharmaceutical composition for the prevention and/or treatment of

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benign prostatic hyperplasia and/or prostatic hypertrophy, a method for the treatment or prevention of benign prostatic hyperplasia/prostatic hypertrophy comprising administering an EGF-receptor antagonist of groups (A), (B) or (C), described herein optionally in combination with known compounds for the treatment of benign prostatic hyperplasia/prostatic hypertrophy, as well as associated pharmaceutical compositions. Excerpt(s): This application claims benefit to U.S. application Ser. No. 60/389,815 filed Jun. 18, 2003. and, in the case of the compounds of groups (A) and (B), optionally the tautomers, the stereoisomers or the salts thereof, particularly the physiologically acceptable salts thereof with inorganic or organic acids or bases, for preparing a pharmaceutical composition for the prevention and/or treatment of benign prostatic hyperplasia (BPH) and/or prostatic hypertrophy, a method for the treatment or prevention of benign prostatic hyperplasia/prostatic hypertrophy comprising administering an EGF-receptor antagonist of groups (A), (B) or (C), optionally in combination with known compounds for the treatment of benign prostatic hyperplasia/prostatic hypertrophy, as well as pharmaceutical compositions comprising an EGF-receptor antagonist of groups (A), (B) or (C) and a known compound for the treatment of benign prostatic hyperplasia/prostatic hypertrophy, selected from the group (D) consisting of osaterone,.alpha.1-adrenoreceptor-antagonists, non-selective and selective muscarine antagonists, LHRH-/GnRH-antagonists or testosterone5.alpha.-reductase inhibitors. The.alpha.1-adrenoreceptor-antagonists used in the combination of active substances according to the invention are preferably the active substances KMD-3231 (silodosin), AIO-8507L, UK-338003, RBX-2258 (parvosin), SNAP6383 (L 771688), GYKI-16084, UK-294315, (S)-doxazosin, tamsulosin, prazosin, naftopidil, terazosin, alfuzosin or indoramin. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Use of neurokinin receptor antagonists to treat androgen-dependent diseases Inventor(s): Berardi, Mark R.; (Sussex, NJ), Cartwright, Mark E.; (Sparta, NJ), Leach, Michael W.; (Shrewsbury, MA), Mirro, Elmer J.; (Wantage, NJ), Pachter, Jonathan A.; (Maplewood, NJ), Reichard, Gregory A.; (Morris Plains, NJ), Sinha, Dineshwar; (Newton, NJ) Correspondence: Schering-Plough Corporation; Patent Department (k-6-1, 1990); 2000 Galloping Hill Road; Kenilworth; NJ; 07033-0530; US Patent Application Number: 20030092602 Date filed: May 7, 2002 Abstract: Use of an antagonist selected from the group consisting of: (a) antagonists of neurokinin-1 (NK.sub.1), neurokinin-2 (NK.sub.2) and neurokinin-3 (NK.sub.3) receptors, (b) antagonists of NK.sub.1 and NK.sub.2 receptors, (c) antagonists of NK.sub.2 and NK.sub.3 receptors, (d) antagonists of NK.sub.1 and NK.sub.3 receptors, (e) antagonists of NK.sub.1 receptors, and (f) antagonists of NK.sub.2 to treat symptoms and disorders associated with a production and/or secretion of androgen. One aspect of the invention relates to the use of antagonists to suppress production/secretion of androgens in mammals suffering from an androgen-dependent disease, such as benign prostatic hyperplasia and prostatic carcinoma. Excerpt(s): The application claims priority to U.S. Provisional Application No. 60/289,491, filed May 8, 2001. The invention is directed to a method of treating an androgen-dependent disease in mammals, e.g., humans, with antagonists of neurokinin-

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1 (NK.sub.1), neurokinin-2 (NK.sub.2) and/or neurokinin-3 (NK.sub.3) receptors. The invention further relates to the use of these antagonists for purposes of prophylactic modulation. An androgen-dependent disease is one which is exacerbated by, or caused by, excessive, inappropriate or unregulated androgen production. Examples of such diseases in men include, but are not limited to, benign prostatic hyperplasia (BPH), metastatic prostatic carcinoma, testicular cancer, androgen dependent acne, male pattern baldness and precocious puberty in boys. Examples of such diseases in women include, but are not limited to, hyperandrogenism, hirsutism, virilization, polycystic ovary syndrome (PCOS), HAIR-AN syndrome (hyperandrogenism, insulin resistance and acanthosis nigricans), ovarian hyperthecosis (HAIR-AN with hyperplasia of luteinized theca cells in ovarian stroma), other manifestations of high intraovarian androgen concentrations (e.g., follicular maturation arrest, atresia, anovulation, dysmenorrhea, dysfunctional uterine bleeding, infertility) and androgen-producing tumors (virilizing ovarian or adrenal tumor). 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 benign prostatic hyperplasia, 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 “benign prostatic hyperplasia” (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 benign prostatic hyperplasia. You can also use this procedure to view pending patent applications concerning benign prostatic hyperplasia. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.

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CHAPTER 5. BOOKS ON BENIGN PROSTATIC HYPERPLASIA Overview This chapter provides bibliographic book references relating to benign prostatic hyperplasia. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on benign prostatic hyperplasia 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 “benign prostatic hyperplasia” (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 benign prostatic hyperplasia: •

Patient's Guide to Urology: Plumbing Problems in Layman's Terms Source: Toledo, OH: High Oaks Publishing Company. 1995. 258 p. Contact: Available from bookstores and libraries and, at the wholesale level, from Baker and Taylor, (908) 722-8000. Also available in orders of 10 or more copies from High Oaks Publishing Company, Center Urology of Toledo, Inc. 3425 Executive Parkway, Suite 214, Toledo, OH 43606. (419) 531-1700. PRICE: $21.95 (cloth); $12.95 (paperback). ISBN: 0964577305 (cloth); 0964577313 (paper). Summary: In this book, the author presents a clear and concise discussion of the functioning of the normal genital and urinary tracts, the common malfunctions resulting from disease, and the principles of treatment. Twenty-eight chapters cover topics including impotence; circumcision; hypospadias; Peyronie's disease; benign prostatic hyperplasia; prostatic cancer; the bladder and urinary incontinence; stress incontinence;

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urethral stenosis; interstitial cystitis; bedwetting; blood in the urine and bladder cancer; toilet training; kidney cysts and cancer; kidney stones; dialysis and kidney transplantation; scrotal problems; testicular cancer and the role of male selfexamination; vasectomy; male fertility problems; infections of the urinary tract; prostatitis; sexually transmitted diseases; and AIDS. A detailed glossary and brief subject index conclude the book. •

Urology for Primary Care Physicians Source: Philadelphia, PA: W.B. Saunders Company. 1999. 399 p. Contact: Available from W.B. Saunders Company. Order Fulfillment, 6277 Sea Harbor Drive, Orlando, FL 32887. (800) 545-2522. Fax (800) 874-6418 or (407) 352-3445. Website: www.wbsaunders.com. PRICE: $52.00 plus shipping and handling. ISBN: 0721671489. Summary: The intent of this book is to present from the urologist's perspective the most cost effective and appropriate approaches for the primary care physician to evaluate and treat or triage patients with urologic problems in the office or emergency department. The book offers a systematic, problem oriented approach and a capsular presentation of highlights and 'take home' messages. The text includes 31 chapters: the anatomic basis of common urologic diseases, a systematic approach to urologic evaluation, laboratory investigations in urology, principles of imaging studies of the genitourinary system, urologic emergencies, the evaluation and management of hematuria (blood in the urine), genitourinary tract trauma, urinary calculus disease, sexually transmitted diseases, upper urinary tract infections (UTIs), UTIs in children, lower UTIs in women, lower UTIs in men, uncommon infections of the genitourinary tract, voiding dysfunction and urinary incontinence in women, voiding dysfunction in men with lower urinary tract symptoms and benign prostatic hyperplasia (BPH), benign prostatic hypertrophy, urologic problems in pregnancy, renal (kidney) function in pregnancy, perinatal urologic consultation, congenital anomalies, pediatric enuresis (bedwetting) and voiding dysfunction, genitourinary malignancies (cancer) in children, prostate specific antigen (PSA), carcinoma of the genitourinary system, the role of primary health care providers in cancer prevention, acute renal failure (ARF), endocrine and metabolic disorders, management of male infertility, sexual dysfunction in the male, and superficial lesions of the male external genitalia. Each chapter includes black and white illustrations and a list of suggested readings. A subject index concludes the text.

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Atlas of Prostatic Diseases Source: New York, NY: Parthenon Publishing Group. 1997. 96 p. Contact: Available from Parthenon Publishing. One Blue Hill Plaza, P.O. Box 1564, Pearl River, NY 10963. (800) 735-4744 or (914) 735-9363. Fax (914) 725-1385. PRICE: $85.00. ISBN: 1850705852. Summary: This atlas brings together text and illustrations to tell the story of the prostate gland and the diseases to which it is prone. The author notes that treatment options at present are ever-changing and often ephemeral. As a consequence, this volume concentrates on the causes and pathology of prostatic disorders, together with the methods available for their diagnosis, rather than on their management and treatment. The first section of the book presents a literary review of the major diseases of the prostate, beginning with the anatomy and embryology of the prostate, and concluding with the diagnostic tests currently available for assessment of the prostate gland. The second section of the atlas contains 109 photomicrographs and diagrammatic illustrations that convey the important concepts related to prostatic diseases. The author

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reminds readers that two common disorders, benign prostatic hyperplasia (BPH) and prostatitis, frequently result in considerable impairment of the quality of life; a third, prostate cancer, is now second only to lung cancer as a cause of cancer death in men. The author hopes that this atlas will provide an accessible format to make more health care providers knowledgeable about the various prostatic diseases. A subject index concludes the volume. 48 references. (AA-M). •

Instructions for Patients. 5th ed Source: Philadelphia, PA: W.B. Saunders Company. 1994. 598 p. Contact: Available from W.B. Saunders Company. Book Order Fulfillment, 6277 Sea Harbor Drive, Orlando, FL 32887-4430. (800) 545-2522. Fax (800) 874-6418. PRICE: $49.95. ISBN: 0721649300 (English); 0721669972 (Spanish). Summary: This book is a compilation of instructions for patients, published in paperback format. Each fact sheet provides information in three sections: basic information, including a description of the condition, frequent signs and symptoms, causes, risk factors, preventive measures, expected outcome, and possible complications; treatment, including general measures, medication, activity guidelines, and diet; and when to contact one's health care provider. Fact sheets are available on kidney and urologic topics including: enuresis; cystitis in women; cystitis in men; bladder or urethra injury; bladder tumor; glomerulonephritis; male impotence; urinary incontinence; stress incontinence; urge incontinence; acute pyelonephritis; chronic kidney infection; polycystic kidney; kidney stones; the nephrotic syndrome; priapism; benign prostatic hyperplasia; prostatitis; acute renal failure; chronic kidney failure; testicular torsion; urethritis; and Kegel exercises. The fact sheets can be photocopied and distributed to patients as a reinforcement of oral instructions and as a teaching tool. The book is available in English or Spanish.

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Prostate: Questions You Have, Answers You Need. Revised ed Source: Allentown, PA: People's Medical Society. 1996. 192 p. Contact: Available from Independent Publishers Group. Order Department, 814 N. Franklin Street, Chicago, IL 60610. (800) 888-4741 or (312) 337-0747. Fax (312) 337-5985. E-mail: [email protected]. PRICE: $12.95. ISBN: 1882606639. Summary: This book provides readers with a consumer's guide to the prostate and to prostatic diseases. After an introductory chapter on the anatomy and physiology of the prostate, the author describes three types of prostatic disease: prostatitis, benign prostatic hyperplasia (BPH), and prostate cancer. The latter section covers stages of prostate cancer, diagnostic tests including rectal exams, the prostate-specific antigen (PSA) test, transrectal ultrasound, and biopsy and other staging tests, and prevention issues. The next chapter reviews the treatment options for BPH, including surgery, its mortality and complications, alternative procedures, medication, and self help. A final chapter describes treatment options for prostate cancer, including surgery, radiation therapy, hormonal therapy, drug therapy, other therapies, nontreatment, treatment according to stage, and followup and recurrence. The book concludes with a section on informational and mutual-aid groups, a glossary of related terms, a list of suggested readings, and a subject index. The book is written in a question and answer format, with nontechnical language used throughout. 7 references.

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Clinical Manual of Urology Source: New York, NY: McGraw-Hill, Inc. 2001. 924 p. Contact: Available from McGraw-Hill, Inc. 1221 Avenue of the Americas, New York, NY 10020. (612) 832-7869. Website: www.bookstore.mcgraw-hill.com. PRICE: $54.95;plus shipping and handling. ISBN: 0071362010. Summary: This handbook serves as a basic, portable reference tool for the busy medical student and house officer rotating on the urology service and enables program directors to use the information presented as a framework on which to present their particular management styles and strategies. In addition, the handbook can serve as a ready reference for the primary care physician, who is often the first person to see the patient with what ultimately proves to be a urologic problem. The handbook offers 31 chapters: anatomy of the urogenital tract; signs and symptoms (the initial examination); diagnostic uroradiology; interventional uroradiology; lower urinary tract infections (UTI) in women; prostatitis (inflamed prostate gland) and lower UTI in men; painful bladder syndromes; pyelonephritis (kidney infections); nephrolithiasis (kidney stones); emergency room urology; urologic trauma; urethral stricture disease; urinary fistulae; voiding function and dysfunction; benign prostatic hyperplasia (BPH, noncancerous overgrowth of the prostate); the physiology of acute and chronic renal (kidney) failure; adult genitourinary cancer; urinary diversion; radiation therapy; male sexual dysfunction; male fertility and infertility; sexually transmitted diseases (STDs); nonmalignant diseases of the retroperitoneum; disorders of the adrenal gland; renal transplantation; renovascular disease; disorders of sexual differentiation (ambiguous genitalia); pediatric oncology (cancer in children); enuresis (bedwetting) and voiding dysfunction in children; congenital anomalies (problems present at birth); and specific infections of the genitourinary tract. The information in each chapter is presented in outline format, for ease of reference. Line drawings and radiographs illustrate the chapters. A detailed subject index concludes the handbook.

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Manual of Urology: Diagnosis and Therapy. 2nd ed Source: Hagerstown, MD: Lippincott Williams and Wilkins. 1999. 362 p. Contact: Available from Lippincott Williams and Wilkins. P.O. Box 1600, Hagerstown, MD 21741. (800) 638-3030 or (301) 714-2300. Fax (301) 824-7390. Website: www.lww.com. PRICE: $37.95 plus shipping and handling. ISBN: 078171785X. Summary: This manual is designed to be used by the house officer and medical student responsible for urology patients. The related endoscopic, medical, and diagnostic procedures are well described. Twenty two chapters cover imaging of the genitourinary tract, radionuclide imaging, endoscopic instruments and surgery, nontraumatic genitourinary emergencies, fluid and electrolyte disorders, lower urinary tract symptoms, hematuria (blood in the urine) and other urine abnormalities, evaluation of renal mass lesions, surgical disorders of the adrenal gland, urinary calculi (stones) and endourology, the management of urinary incontinence, male erectile dysfunction (impotence), male reproductive dysfunction, neoplasms (cancerous and benign) of the genitourinary tract, the medical management of genitourinary malignancy (cancer), radiation therapy of genitourinary malignancy, genitourinary infection, management of genitourinary trauma, pediatric urology, neurourology and urodynamic testing, and renal (kidney) transplantation. Each chapter presents information in outline form, with numerous tables and diagrams, as necessary. Each chapter concludes with a list of suggested reading. The handbook concludes with two appendices, presenting the

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American Urological Association Symptom Score (for benign prostatic hyperplasia) and the staging of genitourinary tumors, as well as a subject index. •

20 Common Problems in Urology Source: New York, NY: McGraw-Hill, Inc. 2001. 335 p. Contact: Available from McGraw-Hill, Inc. 1221 Avenue of the Americas, New York, NY 10020. (612) 832-7869. Website: www.bookstore.mcgraw-hill.com. PRICE: $45.00;plus shipping and handling. ISBN: 0070634130. Summary: This text on common problems in urology is designed for the primary care provider. The text covers both pediatric and adult conditions and features quick reference algorithms, charts and tables that organize presenting signs and symptoms, diagnostic tests, and treatments. Twenty chapters cover fetal and postnatal hydronephrosis (fluid accumulation in the kidneys), urinary tract infections (UTIs) in children, cryptorchidism (undescended testicles), circumcision, nocturnal enuresis (bedwetting), UTIs in adults, urethritis, urinary incontinence, interstitial cystitis, geriatric urology, hematuria (blood in the urine), prostate cancer screening, benign prostatic hyperplasia (BPH), scrotal mass and pain, genital skin rash, urinary calculi (stones), erectile dysfunction (impotence), male infertility, vasectomy, male menopause, and imaging studies (diagnostic tests). Most chapters define the condition and then discuss the differential diagnosis, the physical examination, recommended diagnostic tests, special considerations, treatment options, and patient care strategies. The text also offers practice advice on when to refer to a specialist and what to expect post-referral. The text concludes with a subject index and is illustrated with black and white photographs and diagrams.

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Urologic Prostheses: The Complete Practical Guide to Devices, Their Implantation, and Patient Follow up Source: Totowa, NJ: The Humana Press, Inc. 2002. 328 p. Contact: Humana Press, Inc. 999 Riverview Dr., Suite 208 Totowa, NJ 07512. (973) 2561699. Fax (973) 256-8341. E-mail: [email protected] PRICE: $125.00, plus shipping and handling. ISBN: 0896038947. Summary: This text was compiled to provide a broad view of prosthetic devices used in urologic surgery. In keeping with recent advances in urologic prosthetic surgery, contributors of recognized authority have been assembled to write expert articles for the book. The book offers 18 chapters, on the history of urologic prostheses; tissue engineering for the replacement of urologic organs; injectable agents for urinary incontinence; injectable materials for use in urology; Teflon injection for incontinence after radical prostatectomy; urethral stents for neurogenic bladder dysfunction; Urolume stents in the management of benign prostatic hyperplasia (BPH); testicular prostheses; current status and future of penile prosthesis surgery; semirigid, malleable, and mechanical penile prostheses; inflatable penile prostheses; experience with the Mentor Alpha-1; Peyronie disease and penile implants; current approach to penile prosthesis infection; reoperation for penile prosthesis implantation; corporeal fibrosis, penile prosthesis implantation and corporeal reconstruction; artificial urinary sphincter for treatment of male urinary incontinence; and female incontinence and the artificial urinary sphincter. Each chapter includes black and white photographs and charts, and concludes with a list of references. The text concludes with a subject index.

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Comprehensive Urology Source: Orlando, FL: Mosby, Inc. 2001. 704 p. Contact: Available from Mosby, Inc. Order Fulfillment Department, 6277 Sea Harbor Drive, Orlando FL 32887. (800) 321-5068. Fax (800)874-6418. E-mail: [email protected] Website: www.elsevierhealth.com. PRICE: $249.00. ISBN: 723429499. Summary: This textbook offers a comprehensive overview of urology in one volume incorporating clinical information concerning all aspects of urology. The internationally renowned contributors present detailed clinical information in a format which is not encyclopedic but contains carefully selected and nonbiased practical information backed by specific, relevant references. The first section concisely reviews basic anatomy, physiology, and molecular biology, which have relevance for the entire text. The remaining 42 chapters are presented in seven sections: investigative urology, pediatric urology, benign conditions of the upper urinary tract, urologic oncology, benign conditions of the lower urinary tract, andrology, and miscellaneous. Specific topics include diagnostic tests, interventional uroradiology, congenital diseases, vesicoureteral reflux, renal (kidney) transplantation, urinary tract infections, urinary tract stones, bladder cancer, prostate cancer, benign prostatic hyperplasia, female urology and incontinence, interstitial cystitis, the neuropathic bladder, urinary diversion and augmentations, urethral stricture disease, male infertility, erectile dysfunction, benign and malignant disorders of the penis, extracorporeal shock wave lithotripsy (ESWL), genitourinary trauma, radiation therapy, and chemotherapy. Each chapter concludes with lengthy references, and a subject index concludes the volume. The text is illustrated with full-color photographs and drawings.

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Pathophysiologic Principles of Urology Source: Malden, MA: Blackwell Science. 1994. 528 p. Contact: Available from Blackwell Science, Inc. 350 Main Street, Commerce Place, Malden, MA 02148. (800) 215-1000 or (617) 388-8250. Fax (617) 388-8270. E-mail: [email protected]. PRICE: $55.00. ISBN: 0865422214. Summary: This urology textbook emphasizes pathophysiologic concepts, correlates diagnostic testing with pathophysiology, and documents the scientific basis for the treatment of the common diseases of the genitourinary tract. Eighteen chapters cover topics including embryology; renal physiology; ureteral pathophysiology; bladder function; benign prostatic hyperplasia; male infertility; penile function; basic immunology; renal transplantation; urinary tract infection; antimicrobials in urology; calculi; renal and adrenal causes of hypertension; principles of radiation therapy; chemotherapy; flow cytometry in urologic oncology; urinary diversion; and lymphadenectomy in genitourinary cancers. Each chapter, written by experts in the field, includes tables and figures, as well as an annotated suggested reading list. A subject index concludes the book.

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Urology Annual: Volume 7 Source: Scranton, PA: W.W. Norton and Company. 1993. 358 p. Contact: Available from W.W. Norton and Company. National Book Company, 800 Keystone Industrial Park, Scranton, PA 18512-4601. (212) 354-5500; (800) 233-4830. PRICE: $85. ISBN: 0393710122.

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Summary: This volume, the seventh in an annual series, offers comprehensive and timely presentations of various subjects that are of interest to practicing urologists. Fifteen articles cover topics including the management of carcinoma of the prostate; laparoscopic pelvic node dissection; DNA quantitation; supravesical urinary diversion and bladder diversion; bladder preservation in the management of invasive bladder cancer; systemic cytotoxic chemotherapy in the management of muscle-invasive bladder cancer; oncogenes and tumor suppressor genes in urologic oncology; hyperthermia in the treatment of benign prostatic hyperplasia; human papillomavirus infection and its relationship to carcinoma of the penis; complicated urinary tract infections and the status of the fluoroquinolones; the importance of bacterial biofilms in urology; managing incontinence in the elderly; the diagnosis and management of acute renal failure; cryptorchidism; and the current management of enuresis. A subject index is appended. •

Urology Annual: Volume 6 Source: Scranton, PA: W.W. Norton and Company. 1992. 377 p. Contact: Available from W.W. Norton and Company. National Book Company, 800 Keystone Industrial Park, Scranton, PA 18512-4601. (212) 354-5500; (800) 233-4830. PRICE: $85 (as of 1992). ISBN: 0393710122. Summary: This volume, the sixth in an annual series, offers comprehensive and timely presentations of various subjects that are of interest to practicing urologists. Sixteen articles cover topics including the pharmacologic management of benign prostatic hyperplasia (BPH); prostatic balloon dilatation and hyperthermia for BPH; the role of ultrasound in prostate cancer; prognostic factors in early prostate cancer; therapy for stage C cancer; the limits of resectability of prostate cancer; the management of metastatic prostate cancer; pitfalls in the management of testicular cancer patients and complications of therapy; biologic response modifiers in metastatic renal cell carcinoma; the indeterminate renal mass; new diagnostic modalities for impotence; male infertility; congenital genitourinary anomalies secondary to maternal drug use; renal changes in pregnancy; and the use of artificial intelligence in urologic decision making. A subject index is appended.

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 “benign prostatic hyperplasia” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “benign prostatic hyperplasia” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “benign prostatic hyperplasia” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •

Building and applying a guideline-based performance measurement system benign prostatic hyperplasia : a report resulting from CCQE-AHCPR Guideline Criteria Project, Develop, apply, and evaluate medical review criteria and educational outreach based upon practice guidelines (SuDoc HE 20.6508:B 43/V.1-2) by U.S. Dept

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of Health and Human Services; ISBN: B00010U47S; http://www.amazon.com/exec/obidos/ASIN/B00010U47S/icongroupinterna •

Finasteride, Msd: Innovation in the Management of Benign Prostatic Hyperplasia : Proceedings of a Symposium Held in Seville, Spain by J.E. Altwein, L.J. Denis; ISBN: 3805559143; http://www.amazon.com/exec/obidos/ASIN/3805559143/icongroupinterna

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Prostate enlargement : benign prostatic hyperplasia (SuDoc HE 20.3323/3:P 94) by U.S. Dept of Health and Human Services; ISBN: B00010Y54G; http://www.amazon.com/exec/obidos/ASIN/B00010Y54G/icongroupinterna

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The Prostrate: Benign Prostatic Hyperplasia and Carcinoma: Actual Positions and Future Perspectives by Helpap; ISBN: 313104781X; http://www.amazon.com/exec/obidos/ASIN/313104781X/icongroupinterna

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

Benign Prostatic Hyperplasia (BPH) Source: in Landau, L.; Kogan, B.A. 20 Common Problems in Urology. New York, NY: McGraw-Hill, Inc. 2001. p. 185-198. Contact: Available from McGraw-Hill, Inc. 1221 Avenue of the Americas, New York, NY 10020. (612) 832-7869. Website: www.bookstore.mcgraw-hill.com. PRICE: $45.00;plus shipping and handling. ISBN: 0070634130. Summary: Benign prostatic hyperplasia (BPH) is a condition encountered in most aging men. This benign (non-cancerous) overgrowth of the prostate can result in a multitude of lower urinary tract symptoms including dysuria (painful urination), frequency, urgency, and nocturia (getting up to urinate at night), as well as obstructive symptoms such as slow stream, hesitancy, intermittency, straining to void, sense of incomplete emptying, and terminal and postvoid dribbling. This chapter on BPH is from a text on common problems in urology (written for the primary care provider). The authors caution that these symptoms may occur from a multitude of lower urinary tract disorders in both men and women; not all are specific to BPH alone. The authors cover definitions of the condition, epidemiology (incidence and prevalence), etiology (causes), pathophysiology (what goes wrong), diagnosis and diagnostic tests, the differential diagnosis, and treatment options, including watchful waiting, medical management (drug therapy), and surgical treatment. A patient evaluation and care algorithm is provided. Current selection of treatment for a given individual depends on the severity of symptoms, presence or absence of complications, comorbidity, sexual function, physician experience and preferences, patient biases, and the availability and cost of less invasive devices. 3 figures. 6 tables. 3 references.

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Urolume Stents in the Management of Benign Prostatic Hyperplasia Source: in Carson, C.C., III. Urologic Prostheses: The Complete Practical Guide to Devices, Their Implantation, and Patient Follow up. Totowa, NJ: The Humana Press, Inc. 2002. p. 117-140. Contact: Humana Press, Inc. 999 Riverview Dr., Suite 208 Totowa, NJ 07512. (973) 2561699. Fax (973) 256-8341. E-mail: [email protected] PRICE: $125.00, plus shipping and handling. ISBN: 0896038947. Summary: Benign prostatic hyperplasia is enlargement of the prostate gland which results in symptoms affecting urination, in the absence of malignancy (cancer). This chapter on the use of Urolume stents in the management of benign prostatic hyperplasia (BPH) is from a text that was compiled to provide a broad view of prosthetic devices used in urologic surgery. Transurethral resection of the prostate (TURP) is still the traditional therapy of choice for symptomatic BPH. However, there are some alternative surgical options available for BPH, including the minimally invasive approach using a permanent endoprosthetic stent to tackle the problem of bladder outlet obstruction (secondary to BPH). An example of such a stent is the Urolume stent, which is a mesh of corrosion-resistant nickel superalloy wire woven into a flexible, expandable tube. The authors discuss the history of the Urolume stent, stent insertion, and results from a randomized, controlled trial using this stent. The authors conclude that a permanently implanted Urolume prostatic urethral stent, with its low morbidity (complications) via a reduced operating time and hospital stay, is a safe alternative to TURP. It appears to produce only slightly more postoperative discomfort and pain during intercourse than a TURP, and the majority of such symptoms resolve eventually. The authors note that TURP should still remain as the standard treatment for BPH in the fit, nongeriatric patient until such time when the problems of intrastent hyperplasia and epithelialization failure are resolved and probably when longer term results, with up to 5 years of followup, of the Urolume stents are available. 12 figures. 2 tables. 25 references.

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Interstitial Laser Therapy of Benign Prostatic Hyperplasia Source: in Graham, S.D., Jr., et al., eds. Glenn's Urologic Surgery. 5th ed. Philadelphia, PA: Lippincott Williams and Wilkins. 1998. p. 1111-1117. Contact: Available from Lippincott Williams and Wilkins. P.O. Box 1600, Hagerstown, MD 21741. (800) 638-3030 or (301) 714-2300. Fax (301) 824-7390. Website: lww.com. PRICE: $199.00 plus shipping and handling. ISBN: 0397587376. Summary: Interstitial laser coagulation (ILC) of benign prostatic hyperplasia (BPH) is used to decrease urethral obstruction and both obstructive and irritative symptoms. In this technique, coagulation necrosis (tissue death) is generated well inside the adenoma, rather than at its urethral surface. This chapter on ILC is from an exhaustive textbook on urologic surgery. Candidates for ILC are all patients with moderate and severe voiding symptoms due to mechanical obstruction of the bladder outlet due to BPH who are otherwise candidates for surgical intervention, either transurethral or open. Because ILC has essentially no major morbidity and can be performed with local anesthesia, even high risk patients who are not candidates for transurethral resection of the prostate (TURP) can be considered for ILC treatment. Recurrent or residual BPH after previous prostate surgery, laser treatment, or microwave treatment can also be treated by ILC. The author details the surgical techniques used and the anticipated outcomes. ILC uses Nd:YAG or diode lasers, as they offer relatively deep penetration in water, efficient volumetric heating (permitting necrotic temperatures deep into tissues) and the ability

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to be delivered with flexible optical fibers. ILC can be performed using the transurethral approach or the percutaneous (perineal) approach. Complications include retrograde ejaculation (0 to 12 percent incidence), the need for repeat BPH treatment, transient irritative symptoms, urethral strictures, and uncomplicated urinary tract infections; no study reported any occurrence of impotence (erectile dysfunction) or sustained urinary incontinence. 8 figures. 5 tables. 15 references. •

Tamsulosin: Role in the Management of Benign Prostatic Hyperplasia Source: in Narayan, P. Benign Prostatic Hyperplasia. London, England: Churchill Livingstone. 2000. p. 171-180. Contact: Available from Harcourt Publishers. Foots Cray High Street, Sidcup, Kent DA14 5HP UK. 02083085700. Fax 02083085702. E-mail: [email protected]. Website: www.harcourt-international.com. PRICE: $149.00 plus shipping and handling. ISBN: 0443056374. Summary: Symptomatic benign prostatic hyperplasia (BPH) is a common disease that affects all men with aging. BPH is currently considered a disease that affects the quality of life; therefore, treatments are currently designed to relieve symptoms and reduce side effects. This chapter on the use of the alpha blocker, tamsulosin, in the clinical management of BPH is from a textbook that compiles data and commentary from the world's leading experts in this field. Approximately 80 percent of the patients receiving drug therapy for BPH are prescribed alpha blockers by their primary care physician. The first two selective, long acting alpha 1 receptor antagonists to be approved for treatment of BPH in the United States were terazosin and doxazosin. Tamsulosin hydrochloride (brand name Flomax), a new class of sulfonyl derivative, a uroselective alpha adrenergic blocker, was FDA-approved in 1997. The authors cover the scientific rationale for this drug use, the structure and classification of alpha adrenergic receptors, the clinical pharmacology and pharmacokinetics of tamsulosin, drug interactions, carcinogenesis (development of cancer), adverse reactions to the drug, and clinical studies investigating its use and efficacy. The authors conclude that tamsulosin overall has several advantages over the alpha blockers currently in use. The long action of tamsulosin allows for once a day dosing. Its therapeutic effect, as indicated by improvements in symptoms score, is realized as early as one week after treatment. Additional advantages include the lack of side effects, even in patients at risk of postural hypotension (low blood pressure) such as the elderly and those on multiple cardiac medications, and patients who have comorbid conditions such as diabetes and cardiac disease. Finally, the lower side effect profile of tamsulosin may also allow its use in combination with other relaxants and newer agents in the treatment of lower urinary tract symptoms. 2 tables. 99 references.

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Radiofrequency Thermal Therapy for Benign Prostatic Hyperplasia by Transurethral Needle Ablation of the Prostate Source: in Narayan, P. Benign Prostatic Hyperplasia. London, England: Churchill Livingstone. 2000. p. 269-280. Contact: Available from Harcourt Publishers. Foots Cray High Street, Sidcup, Kent DA14 5HP UK. 02083085700. Fax 02083085702. E-mail: [email protected]. Website: www.harcourt-international.com. PRICE: $149.00 plus shipping and handling. ISBN: 0443056374. Summary: The increasing demand for less invasive and more economical surgical therapies to treat benign prostatic hyperplasia (BPH) has led to the technique of

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transurethral needle ablation (TUNA), which uses radio frequency energy to perform thermotherapy of the prostate. The TUNA system consists of an energy generator, and an endoscopic instrument for delivering energy into the prostate. The machine also has a urethral cooling system to prevent urethral heat injury. The mechanism of TUNA efficacy is believed to be tissue coagulative necrosis (death), which results in scarring, softening, and a decrease in volume of the prostate. This chapter on the use of TUNA in the clinical management of BPH is from a textbook that compiles data and commentary from the world's leading experts in this field. In this chapter, the authors discuss the physical properties and medical and surgical applications of radiofrequency, the use of radiofrequency in BPH, dosimetry research on this technique, the TUNA procedure itself (including anesthesia requirement during TUNA, clinical results, potential variability of results, and possible adverse events), the mechanism of action of TUNA, and cost considerations. The authors conclude that TUNA is an exciting new minimally invasive treatment for symptomatic BPH. The procedure is tolerated well by patients under regional prostatic block in a clinic setting without the need for hospitalization. The treatment has a particular role in elderly patients with high surgical risk. Furthermore, the lack of significant risks, specifically those of urinary incontinence and sexual dysfunction, makes this treatment more attractive than TURP for many patients. 9 figures. 2 tables. 31 references. •

Hormonal Therapy in Benign Prostatic Hyperplasia Source: in Narayan, P. Benign Prostatic Hyperplasia. London, England: Churchill Livingstone. 2000. p. 181-195. Contact: Available from Harcourt Publishers. Foots Cray High Street, Sidcup, Kent DA14 5HP UK. 02083085700. Fax 02083085702. E-mail: [email protected]. Website: www.harcourt-international.com. PRICE: $149.00 plus shipping and handling. ISBN: 0443056374. Summary: The prostate gland is dependent on androgenic (male hormones) stimulation. Depriving the prostate of its testosterone support is an established treatment for benign prostatic hyperplasia (BPH). This chapter on the hormonal therapy in the clinical management of BPH is from a textbook that compiles data and commentary from the world's leading experts in this field. The author describes the development of finasteride, a 5 alpha reductase inhibitor, the studies that investigated the safety and efficacy of finasteride, the use of finasteride to reduce acute urinary retention and the need for surgery, combination therapy, the composition of the prostate response to finasteride, the biological variability of serum prostate specific antigen (PSA) and finasteride, and other types of hormonal therapy used in men with BPH. Approximately one third to one half of patients with BPH who are treated with finasteride in clinical studies have clinically significant improvements, while modest benefits overall were seen in the study population. Uncontrolled studies suggest that the response to therapy may be sustained for up to 6 years, although it is yet to be determined whether the progression of BPH with time can be prevented. Given its minimal side effects, finasteride should be considered an acceptable treatment option for a select group of patients with BPH. There also appears to be a benefit to finasteride in reducing the incidence of acute urinary retention and BPH related surgical interventions by up to nearly 50 percent when used chronically for over 2 years. With regard to prostate cancer, patients should be informed of the effect that finasteride has in lowering serum PSA levels and the potential impact this may have on the detection of prostate cancer. 6 figures. 53 references.

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Health-Related Quality of Life in Men with Benign Prostatic Hyperplasia Source: in Narayan, P. Benign Prostatic Hyperplasia. London, England: Churchill Livingstone. 2000. p. 69-77. Contact: Available from Harcourt Publishers. Foots Cray High Street, Sidcup, Kent DA14 5HP UK. 02083085700. Fax 02083085702. E-mail: [email protected]. Website: www.harcourt-international.com. PRICE: $149.00 plus shipping and handling. ISBN: 0443056374. Summary: This chapter on health related quality of life in men with benign prostatic hyperplasia (BPH) is from a textbook that compiles data and commentary from the world's leading experts in this field. The authors note that, in some men, BPH can lead to lower urinary tract symptoms (LUTS) and other BPH complications (such as acute urinary retention or obstructive uropathy) that can affect the health of the men who have it, giving this condition its morbidity. Without these manifestations, BPH would be more of a histologic curiosity than a disease. The authors discuss the goals of treatment for BPH, how health related quality of life (HRQoL) is defined and measured, disease specific and generic measures of health status, specific measures of health status for BPH, the relationship between anatomic and physiologic measures of BPH severity with LUTS, and changes in LUTS and health status with treatment for BPH. The authors conclude that men with LUTS have decrements in both disease specific and generic measures of HRQoL. LUTS levels correlated better with these higher order health status measures than measures of the anatomic or physiologic severity of BPH. The findings document the morbidity (illness) of this common condition. Treatment can result in improvement in disease specific measures of health status, and treatment with prostatectomy results in improvements in generic measures of health status as well. 5 figures. 2 tables. 75 references.

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Socioeconomics and Trends in the Management of Benign Prostatic Hyperplasia: United States Perspective Source: in Narayan, P. Benign Prostatic Hyperplasia. London, England: Churchill Livingstone. 2000. p. 53-60. Contact: Available from Harcourt Publishers. Foots Cray High Street, Sidcup, Kent DA14 5HP UK. 02083085700. Fax 02083085702. E-mail: [email protected]. Website: www.harcourt-international.com. PRICE: $149.00 plus shipping and handling. ISBN: 0443056374. Summary: This chapter on socioeconomics and trends in the management of benign prostatic hyperplasia (BPH) is from a textbook that compiles data and commentary from the world's leading experts in this field. In addition to the patient and his physician, a third interested party is increasingly becoming a part of decision making in the management of BPH: the payer of the costs of health care. Economic issues surrounding the diagnosis and treatment of BPH are becoming a major area of concern for payers, in view of the prevalence of the disease, an aging population, and the attendant increasing numbers of men in the BPH age range. The issue is further complicated by the recent explosion in the numbers of new emerging strategies of BPH management. The author reviews the current costs of BPH management, changing treatment patterns and their impact on urologists, future costs of BPH, and means of cost containment. The author concludes that the most costly aspect of any strategy of BPH management is its failure rate and lack of durability. Ineffective treatments, even marginally effective treatments, although initially less costly than prostatectomy, become very expensive when the costs of definitive therapies such as surgery must be

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inevitably added to costs incurred during the course of the ineffective or unsuccessful treatment. Proven clinical effectiveness and cost effectiveness, documented in properly performed prospective randomized clinical trials, are essential. 2 figures. 12 tables. 28 references. •

Epidemiology, Natural History, and Pathogenesis of Benign Prostatic Hyperplasia Source: in Narayan, P. Benign Prostatic Hyperplasia. London, England: Churchill Livingstone. 2000. p. 43-52. Contact: Available from Harcourt Publishers. Foots Cray High Street, Sidcup, Kent DA14 5HP UK. 02083085700. Fax 02083085702. E-mail: [email protected]. Website: www.harcourt-international.com. PRICE: $149.00 plus shipping and handling. ISBN: 0443056374. Summary: This chapter on the epidemiology, natural history, and pathogenesis of benign prostatic hyperplasia (BPH) is from a textbook that compiles data and commentary from the world's leading experts in this field. BPH is one of the most common neoplasms affecting men over 50 years of age. If untreated, it can result in acute urinary retention, infection, stones, and upper urinary tract deterioration. Even though several associations and trends have been observed, the etiology, natural history, and pathophysiology of this disease are far from clear. The lack of correlation between histologic BPH, clinical symptoms, and physical obstruction has been a major cause of ambiguity in the understanding of this disease. The authors discuss factors affecting the incidence of BPH, including age, family history, geographic factors, income, testicular function, obesity, hypertension, diabetes mellitus, liver cirrhosis, vasectomy, sexual activity, smoking, alcohol, and diet. A final section of the chapter considers the risk for prostatectomy in men with BPH; an increasing burden of urinary symptoms as men age is an important source of morbidity in BPH as well as an important determinant of risk of prostatectomy. 68 references.

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Open Prostatectomy in Benign Prostatic Hypertrophy Source: in Narayan, P. Benign Prostatic Hyperplasia. London, England: Churchill Livingstone. 2000. p. 369-379. Contact: Available from Harcourt Publishers. Foots Cray High Street, Sidcup, Kent DA14 5HP UK. 02083085700. Fax 02083085702. E-mail: [email protected]. Website: www.harcourt-international.com. PRICE: $149.00 plus shipping and handling. ISBN: 0443056374. Summary: This chapter on the use of open prostatectomy (removal of the prostate) in the clinical management of benign prostatic hyperplasia (BPH) is from a textbook that compiles data and commentary from the world's leading experts in this field. Simple prostatectomy is an efficient, highly effective, and safe surgical treatment for benign obstructive prostatic disease. Successful surgical outcomes remain reliant on proper patient selection and adherence to proven surgical principles. The frequency of this procedure has decreased with the advent of improved endoscopic instruments, drug therapy, and minimally invasive procedures, together with early detection and treatment of incipient BPH. The authors discuss patient assessment and indications, the preoperative management of the patient, selection of open prostatectomy procedure, the transvesical (suprapubic) prostatectomy, transcapsular (retropubic) prostatectomy, and the complications of open prostatectomy. The authors estimate that open prostatectomy is a procedure which is required in approximately 3 to 5 percent of patients with obstructive BPH. The open prostatectomy techniques have surgical morbidity

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(complications) associated with an abdominal incision, requirement of anesthesia, possible blood transfusions, and wound related problems; other complications can include postoperative urinary incontinence and erectile dysfunction. Each step of the surgical procedures under discussion is illustrated with line drawings. 12 figures. 4 tables. 20 references. •

Transurethral Resection of the Prostate for Benign Prostatic Hyperplasia Source: in Narayan, P. Benign Prostatic Hyperplasia. London, England: Churchill Livingstone. 2000. p. 355-367. Contact: Available from Harcourt Publishers. Foots Cray High Street, Sidcup, Kent DA14 5HP UK. 02083085700. Fax 02083085702. E-mail: [email protected]. Website: www.harcourt-international.com. PRICE: $149.00 plus shipping and handling. ISBN: 0443056374. Summary: Transurethral resection of the prostate (TURP) is a procedure used to prevent unnecessary damage to the bladder and kidneys of men with benign prostatic hyperplasia (BPH). This chapter on TURP in the clinical management of BPH is from a textbook that compiles data and commentary from the world's leading experts in this field. The author considers the indications for TURP; the need for informed consent, particularly addressing the potential problems of retrograde ejaculation and erectile dysfunction (impotence); contraindications to transurethral resection; patient preparation, including position on the operating table; equipment, including irrigating fluid, diathermy, avoiding deep venous thrombosis, and anesthesia; the techniques used for TURP, including preliminary cystourethroscopy, internal urethrotomy, preliminary diathermy of the prostatic arteries, finding the landmarks, resecting the left lateral lobe, the capsule, hemostasis, the second lateral lobe, completing the procedure, and catheterization; complications that may be encountered during the procedure, including hemorrhage, perforation, and erection; postoperative complications, including reactionary hemorrhage, secondary hemorrhage, the transurethral resection syndrome, and incontinence; and dealing with the long term aftermath of cardiac disease. Each step of the surgical procedure is illustrated with line drawings. 24 figures. 41 references.

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Stents in Benign Prostatic Hyperplasia: The United States Experience Source: in Narayan, P. Benign Prostatic Hyperplasia. London, England: Churchill Livingstone. 2000. p. 317-322. Contact: Available from Harcourt Publishers. Foots Cray High Street, Sidcup, Kent DA14 5HP UK. 02083085700. Fax 02083085702. E-mail: [email protected]. Website: www.harcourt-international.com. PRICE: $149.00 plus shipping and handling. ISBN: 0443056374. Summary: While transurethral resection of the prostate (TURP) is the gold standard for the treatment of bladder outlet obstruction (BOO), it is associated with certain complications. Urinary stents, however, offer safe and effective alternatives in the poor surgical risk patient with BOO or in those patients with obstructive prostatic carcinoma (prostate cancer). This chapter on the use of stents for the clinical management of benign prostatic hyperplasia (BPH) is from a textbook that compiles data and commentary from the world's leading experts in this field. The authors discuss both temporary and permanent prostatic urethral stents, and the 5 year results of the North American Multicenter clinical trial using the UroLume permanent stent for patients with BOO. The ideal stent is easy to insert and remove, self-expanding, has a large internal diameter (large enough to be able to pass a cystoscope through it), and is constructed of

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material that is biocompatible and the least subject to corrosion. A major side effect of the original metallic stents was encrustation and obstruction. In subsequent models, this has been resolved by having the stent woven in mesh form, which allows tissue to grow through and epithelialize the internal surface. In the US, the only stent that has FDA approval is the UroLume wallstent, a stent made of a superalloy of steel in mesh form, which is inserted using a special cystoscopically guided device. The stent is available in three different lengths (2, 3, 4 cm) to accommodate varying lengths of urethral strictures. The downside appears to be the irritative symptoms that up to 30 percent of patients experience, and the operative procedure required to remove it when necessary. However, stents appear to be effective treatment in patients who are poor candidates for surgery. 5 figures. 1 table. 26 references.

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CHAPTER 6. MULTIMEDIA ON BENIGN PROSTATIC HYPERPLASIA Overview In this chapter, we show you how to keep current on multimedia sources of information on benign prostatic hyperplasia. We start with sources that have been summarized by federal agencies, and then show you how to find bibliographic information catalogued by the National Library of Medicine.

Video Recordings An excellent source of multimedia information on benign prostatic hyperplasia is the Combined Health Information Database. You will need to limit your search to “Videorecording” and “benign prostatic hyperplasia” using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find video productions, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Videorecording (videotape, videocassette, etc.).” Type “benign prostatic hyperplasia” (or synonyms) into the “For these words:” box. The following is a typical result when searching for video recordings on benign prostatic hyperplasia: •

BPH: Aging and the Enlarged Prostate Source: Princeton, NJ: Films for the Humanities and Sciences. 2000. (videorecording). Contact: Available from Films for the Humanities and Sciences. PO Box 2053, Princeton, NJ 08543-2053. (800) 257-5126. Fax: (609) 275-3767. Email: [email protected]. Website: www.films.com. PRICE: $89.95. Item number: BVL11203. Summary: As they get older, most men will experience benign prostatic hyperplasia, a non-malignant (non-cancerous) enlargement of the prostate gland. This videotape program offers timely facts about a condition frequently left undiscussed until severe urinary discomfort forces the patient to the doctor's office. The program covers the symptoms of BPH, current drug and surgical interventions, and future treatment options; the program emphasizes the importance of an annual prostate exam for men over the age of 50. Commentary is provided by Dr. Claus Roehrborn (University of

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Texas Southwestern Medical Center) and Dr. J. Curtis Nickel (Kingston General Hospital, Ontario). •

Benign Prostatic Hyperplasia: AHCPR Clinical Practice Guideline Source: Secaucus, NJ: Network for Continuing Medical Education (NCME). 1994. Contact: Available from NCME. One Harmon Plaza, Secaucus, NJ 07094. (800) 223-0272 or, in New Jersey, (800) 624-2102, or (201) 867-3550. PRICE: $50 for 2-week rental or $75 for purchase. Available only to NCME subscribers; subscriber fees as of 1995 are $1,920 for VHS subscription, $2,120 for U-matic subscription. Summary: In this continuing education videotape, Dr. John Wasson presents highlights of the 1994 Clinical Practice Guidelines and how to implement them. Topics include epidemiology, including incidence, the number of surgeries, and the use of drug therapies; the diagnostic process, including the initial evaluation, patient history, physical examination, use of the AUA Symptom Index, symptom assessment, urinalysis, serum creatinine test, and prostate-specific antigen (PSA) test; the symptoms of prostatism; optional tests used in diagnosis; patient education and the patient's role in decision-making; noninvasive therapeutic options, including watchful waiting, alpha blocker drugs, finasteride, and lifestyle changes; invasive therapeutic options, including balloon dilation and surgery; the success and failure rates for each therapeutic option, including the probability of retrograde ejaculation; investigational modalities, including hyperthermia, thermal therapy, laser prostatectomy, hormonal manipulation, and prostatic stents; and a review of treatment recommendations.

•

What You Really Need to Know About Enlarged Prostate Source: [Toronto, ON, Canada]: Videos for Patients. 1994. (videocassette). Contact: Available from Medical Audio Visual Communications, Inc. Suite 240, 2315 Whirlpool Street, Niagara Falls, NY 14305. Or P.O. Box 84548, 2336 Bloor Street West, Toronto, ON M6S 1TO, Canada. (800) 757-4868 or (905) 602-1160. Fax (905) 602-8720. PRICE: $99.00 (Canadian); contact producer for current price in American dollars. Order Number VFP023. Summary: This videotape provides viewers with information about prostate enlargement. The videotape is introduced with a brief sketch featuring comedian John Cleese and Dr. Robert Buckman illustrating the difficulties sometimes experienced by patients during the traditional doctor's explanation. Dr. Buckman presents the medical facts using visual aids. Topics include why the prostate becomes enlarged, problems caused by an enlarged prostate, treatment options, including the details of various surgical options and nonsurgical hormone treatments, and the side effects and aftereffects of the different types of treatment. (AA-M).

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CHAPTER 7. PERIODICALS AND NEWS ON BENIGN PROSTATIC HYPERPLASIA Overview In this chapter, we suggest a number of news sources and present various periodicals that cover benign prostatic hyperplasia.

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

Sanofi drug for benign prostatic hyperplasia gets U.S. approval Source: Reuters Medical News Date: June 16, 2003

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•

Dutasteride for benign prostatic hypertrophy successful in phase III trial Source: Reuters Medical News Date: February 25, 2002

•

Glaxo files dutasteride for enlarged prostate in Europe Source: Reuters Industry Breifing Date: October 04, 2001

•

Laserscope benign prostatic hyperplasia system cleared by FDA Source: Reuters Industry Breifing Date: May 10, 2001

•

Prostate Cancer: Benign prostatic hyperplasia not a premalignant lesion Source: Reuters Medical News Date: September 10, 1998

•

Long-Term Morbidity After Thermotherapy For Benign Prostatic Hyperplasia "Acceptably Low" Source: Reuters Medical News Date: November 21, 1996

•

Terazosin Better Than Finasteride In Subset Of Benign Prostatic Hyperplasia Patients Source: Reuters Medical News Date: August 22, 1996 The NIH

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

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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 “benign prostatic hyperplasia” (or synonyms). If you know the name of a company that is relevant to benign prostatic hyperplasia, you can go to any stock trading Web site (such as http://www.etrade.com/) and search for the company name there. News items across various news sources are reported on indicated hyperlinks. Google offers a similar service at http://news.google.com/. BBC Covering news from a more European perspective, the British Broadcasting Corporation (BBC) allows the public free access to their news archive located at http://www.bbc.co.uk/. Search by “benign prostatic hyperplasia” (or synonyms).

Newsletters on Benign Prostatic Hyperplasia Find newsletters on benign prostatic hyperplasia using the Combined Health Information Database (CHID). You will need to use the “Detailed Search” option. To access CHID, go to the following hyperlink: http://chid.nih.gov/detail/detail.html. Limit your search to “Newsletter” and “benign prostatic hyperplasia.” 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.” Type “benign prostatic hyperplasia” (or synonyms) into the “For these words:” box. The following list was generated using the options described above: •

Benign Prostatic Hyperplasia: A New Look at an Old Problem Source: Focus on Geriatric Care and Rehabilitation. 7(3): 1-8. July/August, 1993. Summary: Benign prostatic hyperplasia (BPH) is the noncancerous enlargement of the prostate. This newsletter focuses on BPH, discusses its etiology and pathophysiology; screening and prevention; the clinical manifestations of BPH; the secondary effects of BPH; the diagnosis of BPH, including laboratory tests, radiographic tests and miscellaneous tests; the treatment of BPH, including medical management, surgical management, preprostatectomy education, transurethral resection of the prostate, suprapubic resection, retropubic resection, and the perineal approach; and postprostatectomy care in the extended care facility. A pull-out sheet summarizes recommended postprostatectomy education topics and their rationale. 4 figures. 4 tables.

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

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prefer. For the format option, select “Newsletter Article.” Type “benign prostatic hyperplasia” (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 benign prostatic hyperplasia: •

Enlarged Prostate Gland: Many Treatment Options Source: Mayo Clinic Health Letter. 19(4): 1-3. April 2001. Contact: Available from Mayo Clinic Health Letter. Subscription Services, P.O. Box 53889, Boulder, CO 80322-3889. (800) 333-9037 or (303) 604-1465. Summary: This health newsletter article discusses enlarged prostate gland (benign prostatic hyperplasia), a common problem that affects half of men in their 60s and close to 80 percent of men in their 80s. The prostate gland is located just below the bladder and surrounds the urethra, the tube that drains the bladder. This gland often enlarges with age and constricts the urethra, making it more difficult for urine to pass through. Signs and symptoms of benign prostatic hyperplasia (BPH) may include excessive urination at night, a weak urine stream, stopping and starting while urinating, a frequent urge to urinate, and a feeling that the bladder has not been emptied completely. Diagnosis includes a symptom questionnaire, a urine test to rule out infection, a prostate specific antigen (PSA) test, and a digital rectal exam (DRE) to rule out prostate cancer, and sometimes more tests including cystoscopy and urine flow tests. Generally, no treatment is required for mild BPH symptoms. Monitoring the situation and simple lifestyle changes may be all that is necessary. For men with moderate to severe symptoms, treatment options include oral medications, surgery, and minimally invasive techniques. Drug options include alpha blockers, finasteride, and plant extracts (including saw palmetto). Surgical treatments include transurethral resection of the prostate (TURP), transurethral incision of the prostate (TUIP), open prostatectomy (removal of the prostate), microwave and radiofrequency, laser therapy, and stents. One sidebar summarizes lifestyle changes that may be recommended to help men deal with symptoms of BPH. 1 figure. 1 table.

Academic Periodicals covering Benign Prostatic Hyperplasia Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to benign prostatic hyperplasia. In addition to these sources, you can search for articles covering benign prostatic hyperplasia 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 8. 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 benign prostatic hyperplasia. 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 benign prostatic hyperplasia. 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,

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etc.). The following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to benign prostatic hyperplasia: Alfuzosin •

Systemic - U.S. Brands: Uroxatral; http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/500487.html

Doxazosin •

Systemic - U.S. Brands: Cardura http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202629.html

Dutasteride •

Systemic - U.S. Brands: Avodart http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/500429.html

Finasteride •

Systemic - U.S. Brands: Propecia; Proscar http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202649.html

Phenoxybenzamine •

Systemic - U.S. Brands: Dibenzyline http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202458.html

Prazosin •

Systemic - U.S. Brands: Minipress http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202475.html

Tamsulosin •

Systemic - U.S. Brands: Flomax http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203479.html

Terazosin •

Systemic - U.S. Brands: Hytrin http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202546.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/.

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PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html. Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee. 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 Institute10: •

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/

10

These publications are typically written by one or more of the various NIH Institutes.

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•

National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm

•

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

•

National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm

•

National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/

•

National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/

•

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm

•

National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html

•

National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm

•

National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm

•

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

•

National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html

•

National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm

•

Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp

•

National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/

•

National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp

•

Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html

•

Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm

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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.11 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:12 •

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

11

Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 12 See http://www.nlm.nih.gov/databases/databases.html.

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•

Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html

•

Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html

The NLM Gateway13 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.14 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “benign prostatic hyperplasia” (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 13094 203 836 36 21 14190

HSTAT15 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.16 These documents include clinical practice guidelines, quickreference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.17 Simply search by “benign prostatic hyperplasia” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

13

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

14

The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH). 15 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 16 17

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

Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations.

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Coffee Break: Tutorials for Biologists18 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.19 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.20 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.

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

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

•

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

18 Adapted 19

from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html.

The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 20 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process.

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APPENDIX B. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. Since new guidelines on benign prostatic hyperplasia 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 benign prostatic hyperplasia. 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 benign prostatic hyperplasia. 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 “benign prostatic hyperplasia”:

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Bladder Diseases http://www.nlm.nih.gov/medlineplus/bladderdiseases.html Breast Diseases http://www.nlm.nih.gov/medlineplus/breastdiseases.html Kidney Diseases http://www.nlm.nih.gov/medlineplus/kidneydiseases.html Prostate Cancer http://www.nlm.nih.gov/medlineplus/prostatecancer.html Prostate Diseases http://www.nlm.nih.gov/medlineplus/prostatediseases.html Urinary Tract Infections http://www.nlm.nih.gov/medlineplus/urinarytractinfections.html

Within the health topic page dedicated to benign prostatic hyperplasia, the following was listed: •

Diagnosis/Symptoms Genital Problems in Men Source: American Academy of Family Physicians http://familydoctor.org/539.xml Hematuria (Blood in the Urine) Source: National Kidney and Urologic Diseases Information Clearinghouse http://kidney.niddk.nih.gov/kudiseases/pubs/hematuria/index.htm Medical Tests for Prostate Problems Source: National Kidney and Urologic Diseases Information Clearinghouse http://kidney.niddk.nih.gov/kudiseases/pubs/prostatetests/index.htm Prostate Cancer Screening: Know Your Options Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=HQ01273 PSA Levels: Can They Rise after Prostate Removal? Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=HO00032 Questions and Answers about the Prostate-Specific Antigen (PSA) Test Source: National Cancer Institute http://cis.nci.nih.gov/fact/5_29.htm Ultrasound-Pelvis Source: American College of Radiology, Radiological Society of North America http://www.radiologyinfo.org/content/ultrasound-pelvis.htm

•

Treatment About Prostatectomy (For Benign Prostatic Hyperplasia) Source: American College of Surgeons http://www.medem.com/MedLB/article_detaillb.cfm?article_ID=ZZZBLD85IWC &sub_cat=302

Patient Resources

Enlarged Prostate: What Are Your Treatment Choices? Source: American Foundation for Urologic Disease http://www.afud.org/conditions/enlargedprostate1.asp Prostate Surgery - TURP http://www.nlm.nih.gov/medlineplus/tutorials/turploader.html •

Alternative Therapy Recall of PC SPES and SPES Dietary Supplements Source: National Center for Complementary and Alternative Medicine http://nccam.nih.gov/health/alerts/spes/index.htm Saw Palmetto Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=SA00058

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Specific Conditions/Aspects Ask the CPDR: Questions from Our Patients and Answers Source: Center for Prostate Disease Research http://www.cpdr.org/ask.shtml Gold, Clumpy Sperm: What Does It Mean? Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=AN00779 Prostatitis: Disorders of the Prostate Source: National Kidney and Urologic Diseases Information Clearinghouse http://kidney.niddk.nih.gov/kudiseases/pubs/prostatitis/index.htm What Is Prostatitis? Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=DS00341

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From the National Institutes of Health Prostate Problems Source: National Institute on Aging http://www.niapublications.org/engagepages/prostate.asp Understanding Prostate Changes: A Health Guide for All Men Source: National Cancer Institute http://www.cancer.gov/cancerinfo/understanding-prostate-changes/ What I Need to Know about Prostate Problems Source: National Kidney and Urologic Diseases Information Clearinghouse http://kidney.niddk.nih.gov/kudiseases/pubs/prostate_ez/index.htm

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Organizations American Foundation for Urologic Disease http://www.afud.org/ National Institute of Diabetes and Digestive and Kidney Diseases http://www.niddk.nih.gov/

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National Institute on Aging http://www.nia.nih.gov/ National Kidney and Urologic Diseases Information Clearinghouse Source: National Institute of Diabetes and Digestive and Kidney Diseases http://kidney.niddk.nih.gov/ •

Research Combined Drug Therapy Prevents Progression of Prostate Enlargement Helps Men at High Risk Avoid Surgery Source: National Institute of Diabetes and Digestive and Kidney Diseases http://www.nih.gov/news/pr/dec2003/niddk-17.htm Two-Drug Therapy is Best for Symptomatic Prostate Enlargement Source: National Institute of Diabetes and Digestive and Kidney Diseases http://www.nih.gov/news/pr/may2002/niddk-28.htm

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Statistics FASTATS: Prostate Disease Source: National Center for Health Statistics http://www.cdc.gov/nchs/fastats/prostate.htm Kidney and Urologic Disease Statistics for the United States Source: National Kidney and Urologic Diseases Information Clearinghouse http://kidney.niddk.nih.gov/kudiseases/pubs/kustats/index.htm

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Women For Women Who Care: Information on Prostate Disease to Share with the Men in Your Life Source: American Foundation for Urologic Disease http://www.afud.org/conditions/forwomen.asp

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 benign prostatic hyperplasia. 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:

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Benign Prostatic Hyperplasia: Diagnosis and Treatment Source: Silver Spring, MD: Agency for Health Care Policy and Research. 1994. 13 p. Contact: Available from Agency for Health Care Policy and Research Publications Clearinghouse. P.O. Box 8547, Silver Spring, MD 20907. (800)358-9295. PRICE: Single copy free. Summary: Benign prostatic hyperplasia (BPH) is the most common benign neoplasm in the aging human male. This quick reference guide, excerpted from the Clinical Practice Guideline, was developed to apply to the typical man over age 50 with symptoms of prostatism, but with no significant medical morbidities such as diabetes or other known causes of voiding dysfunction. The guide includes diagnostic issues; the Symptom Index of the American Urological Association; treatment modalities; a decision diagram; and a balance sheet of treatment outcomes. The guideline details the relative benefits and harms associated with all diagnostic and treatment approaches. Treatment options discussed include: watchful waiting, alpha blocker and finasteride medications, balloon dilatation, and the surgical options of transurethral incision, transurethral resection, and open prostatectomy. 3 figures. (AA-M).

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Answers to Your Questions About Having an Enlarged Prostate Source: Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc. 1998. [9 p.]. Contact: Available from Boehringer Ingelheim Pharmaceuticals, Inc. Ridgefield, CT 06877. Website: http://www.boehringer-ingelheim.com/. PRICE: Single copy free. Summary: This booklet helps readers understand benign prostatic hyperplasia (BPH) and the use of tamsulosin hydrochloride (Flomax) to treat BPH. The booklet describes BPH and dispels myths about the conditions then explains how BPH is diagnosed with symptoms and a digital rectal examination (DRE). The booklet outlines the common symptoms of BPH, which can include waking up several times during the night to urinate, having a greater urge to urinate or more difficulty postponing urination, a weak flow of urine, difficulty getting urination started, difficulty controlling the starts and stops of the urine stream, a sense of incomplete emptying of the bladder, and losing urine just after emptying the bladder. Treatment options are outlined and include transurethral needle ablation of the prostate (TUNA), transurethral vaporization of the prostate (TUVP), transurethral resection of the prostate (TURP), transurethral incision of the prostate (TUIP), and open prostatectomy (removal of the prostate). The remainder of the booklet describes the use of tamsulosin hydrochloride, which relieves the symptoms of an enlarged prostate by relaxing the muscle in the prostate and the neck of the bladder. A summary of the prescribing information for this drug is printed and enclosed with the booklet. 1 figure. 2 references.

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Treating Your Enlarged Prostate: Benign Prostatic Hyperplasia Patient Guide Source: Rockville, MD: Agency for Health Care Policy and Research. 1994. 21 p. Contact: Available from AHCPR Publications Clearinghouse. P.O. Box 8547, Silver Spring, MD 20907. (800) 358-9295. PRICE: Single copy free. Summary: This booklet is designed to help readers understand benign prostatic hyperplasia (BPH) and how it can be treated. The booklet describes the benefits and risks of the various treatments available for BPH. Specific topics include a description of the anatomy and physiology of the prostate; a definition of BPH; the symptoms and etiology of BPH; how to know when to consult a health care provider; diagnostic tests

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used to confirm BPH; and treatment choices, including watchful waiting, alpha blocker treatment, finasteride drug treatment, balloon dilation, and surgery. One chart summarizes the outcomes of these five BPH treatments. 8 figures. •

Treatment Choices for BPH: Enlarged Prostate Source: Baltimore, MD: Prostate Health Council. American Foundation for Urologic Disease. 1996. 10 p. Contact: Available from American Foundation for Urologic Disease. 1126 North Charles Street, Baltimore, MD 21201. (800) 242-2383 or (410) 468-1800. Fax (410) 468-1808. Website: www.afud.org. PRICE: Single copy free. Summary: This booklet was written to help patients make informed choices about treatment options for their benign prostatic hyperplasia (BPH). The brochure begins with a description of the prostate and its role. More than half of men over age 60 have BPH, an enlarged prostate that is not cancerous. BPH affects the inner part of the prostate first. As a result, the prostate may begin to squeeze the urethra. This sometimes causes problems in urinating. BPH generally does not interfere with sexual functioning. BPH should be treated only if the symptoms are severe enough to affect lifestyle or if the urinary tract is seriously affected. Currently, the main ways of dealing with BPH are watchful waiting, alpha-blocker drug treatment, finasteride drug treatment, and surgery. Surgery often does the best job of relieving symptoms, but it also has more risk than the other treatments. The brochure also describes laser surgery and other new treatments, including electrovaporization and thermal therapy. The brochure outlines the benefits and risks of each type of traditional therapy. The booklet concludes with a glossary of related terms; a pretest and answers are also included.

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Enlarged Prostate Gland: What You Should Know Source: Emeryville, CA: Parlay International. 199x. [1 p]. Contact: Available from Parlay International. P.O. Box 8817, Emeryville, CA 94662-0817. (800) 457-2752. Fax (510) 601-1008. E-mail: [email protected]. Website: www.parlay.com. PRICE: Single copy free. Summary: This brief fact sheet offers basic information about enlarged prostate glands (benign prostatic hyperplasia, or BPH). When the prostate gland becomes enlarged, it can partially or entirely block the urethra, making urination difficult or impossible. The prostate enlarges normally as part of the aging process, starting in a man's late 40s. The fact sheet reviews the symptoms of BPH, tests that will be performed to confirm a diagnosis of BPH, and treatment options. The most common form of treatment for an enlarged prostate is oral medication. Surgery is also a successful method of treatment (usually transurethral prostate resection), but can adversely affect sexual potency and control of urination. Readers are encouraged to have a yearly digital rectal examination to detect and monitor an enlarged prostate. 1 figure.

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Enlarged Prostate: BPH and Male Urinary Problems Source: Baltimore, MD: American Foundation for Urologic Disease. 1998. 12 p. Contact: Available from American Foundation for Urologic Disease (AFUD). 1128 North Charles Street, Baltimore, MD 21201. (800) 242-2383. Website: www.afud.org. PRICE: $13.00 for pack of 50; plus shipping and handling.

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Summary: This brochure describes a particular prostate disease: noncancerous enlargement of the prostate or benign prostatic hyperplasia (BPH). Topics include the anatomy and physiology of the prostate, a definition of BPH, the symptoms of BPH, how it is diagnosed, how it differs from prostate cancer, when to see a specialist, when BPH requires treatment, surgical treatment, nonsurgical treatments, and lifestyle issues. A brief quiz at the beginning of the brochure emphasizes the information that all men should know. The prostate is a gland of the male reproductive system; the gland is made up largely of muscular and glandular tissues and its main function is to produce fluid for semen, which transports sperm. The symptoms of BPH can include a weak urinary stream, difficulty starting urination, interruption of the stream (stopping and starting), pain or burning on urination, urgency (difficulty postponing urination), frequent urination, and awakening frequently at night to urinate. Diagnostic methods include a thorough medical history and the physical examination, including the digital rectal examination. For BPH, if men are not bothered by their symptoms, they may just be put on a program of watchful waiting, which entails regular followup but no actual treatment. Other treatments are drug therapy, thermal (heat based) therapy, surgery, and alternative treatments (such as herbal remedies). The brochure describes the four types of surgery that may be used for BPH: transurethral resection of the prostate (TURP), transurethral incision of the prostate (TUIP), open prostatectomy (removal of the prostate), and laser surgery. The brochure reiterates the differences between BPH and prostate cancer and cautions readers that they must stay vigilant for the signs of prostate cancer, which is best treated when detected early. The brochure concludes with a glossary of terms used in the text and the answers to the pretest. 5 figures. •

Enlarged Prostate: Medication or Surgery Source: Hanover, MD: American Prostate Society. 1994. 4 p. Contact: Available from American Prostate Society. 1340-F Charwood Road, Hanover, MD 21076-3169. (410) 859-3735. E-mail: [email protected]. Web site: http://www.ameripros.org. PRICE: Single copy free; bulk copies available. Summary: This brochure helps men with prostatic enlargement make the decision between medications or surgery for treatment. The brochure first describes the use of flutamide, finasteride (Proscar), and terazosin (Hytrin) and the drawbacks to each. The authors discuss two main objections to medication: cost factors and the lack of opportunity to detect prostatic cancer. The man's health, age, and degree of prostatic enlargement will affect the decision regarding treatment modality. Up to half of all men, properly evaluated for medication, could avoid surgery using Proscar or Hytrin under a physician's care. The remainder of the brochure outlines the steps taken prior to, during, and after surgery for prostatic enlargement. More than 400,000 men each year undergo surgery to correct prostate enlargement, at a cost of more than three billion dollars per year. The brochure lists the conditions that might require surgery (as opposed to watchful waiting): hesitating or difficult urination; incomplete voiding; recurring bladder infections; inability to control urination; and reduced kidney function. The brochure focuses on the transurethral resection of the prostate, or TURP, procedure. One series of diagrams illustrates how the enlarging prostate affects urination at different points in its enlargement. 5 references. (AA-M).

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When You Need An Operation: About Prostatectomy (for Benign Prostatic Hyperplasia) Source: Chicago, IL: American College of Surgeons. 1993. 4 p.

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Contact: Available from American College of Surgeons. 55 East Erie Street. Chicago, IL 60611. PRICE: $14 for 50 copies; $27 for 100 copies. Summary: This brochure provides detailed information for patients about to undergo prostatectomy for benign prostatic hyperplasia (BPH). Topics covered include the anatomy and physiology of the prostate gland; the problem of BPH and symptoms it can cause; the rationale for surgery; the risks and benefits of surgery; how to determine if prostatectomy is indicated; the types of prostate procedures, including transurethral resection of the prostate (TURP), transurethral incision of the prostate (TUIP), and laser treatment; short-term recovery after prostatectomy; and quality of life issues after prostatectomy, such as rehabilitation, sexual function, diet therapy, and continued monitoring of the prostate. The brochure also includes a brief description of the process through which surgeons are certified and reminds readers of the importance of choosing a board-certified surgeon. 1 figure. •

Man's Guide to Thermotherapy for Benign Prostatic Hyperplasia (BPH) Source: Cambridge, MA: EDAP Technomed, Inc. 199x. 2 p. Contact: Available from EDAP Technomed, Inc. 179 Sidney Street, Cambridge, MA 02139. (800) 933-TUMT. PRICE: Single copy free. Summary: This brochure provides readers with a guide to the use of thermotherapy for treating benign prostatic hyperplasia (BPH). Written in a question-and-answer format, the brochure covers the anatomy and physiology of the prostate gland, the incidence of BPH, treatment options (medication and surgery), a definition of thermotherapy, what to expect during the thermotherapy procedure (in terms of time of the procedure, heat, pain), safety concerns, side effects of thermotherapy, the impact of thermotherapy on sexual or urinary functioning, and how to make the decision about thermotherapy. 1 figure.

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Benign Prostatic Hypertrophy Source: in Sodeman, W.A., Jr. Instructions for Geriatric Patients. Philadelphia, PA: W.B. Saunders Company. 1995. p. 253-254. Contact: Available from W.B. Saunders Company. Order Fulfillment, 6277 Sea Harbor Drive, Orlando, FL 32887. (800) 545-2522. Fax (800) 874-6418 or (407) 352-3445. PRICE: $38.95. ISBN: 0721643353. Summary: This chapter, from a handbook of instructions for older people and their caregivers, provides an overview of benign prostatic hypertrophy. As men get older, the prostate gland gets larger, a condition known as benign prostatic hyperplasia (BPH). In some men, an enlarged prostate may cause problems because it can put pressure on the bladder, resulting in the frequent release of small quantities of urine. Sometimes the interference of the enlarged prostate with the bladder area causes minor incontinence, or dribbling. Other symptoms may be hesitancy, frequency of urination, nocturia (increased urination at night), and urgency. Surgical removal of part of the enlarged prostate is the usual treatment for BPH. An alternative, nonsurgical treatment with drugs alone can be used when surgery poses a risk to the patient. Drugs used include finasteride (Proscar), which acts by decreasing the level of a male hormone in the prostate gland, and terazosin (Hytrin), which relaxes the muscles where the bladder empties, reducing the obstruction caused by prostate gland enlargement. The section concludes with a description of the symptoms which should prompt a call to the health care provider's office. These include a change in the ability to urinate, blood in the urine,

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loss of sex drive, weakness or dizziness, and nasal stuffiness (terazosin-treated patients). The chapter appears in large print text to promote ease of reading. (AA-M). •

Benign Prostatic Hyperplasia (BPH): A Guide for Men Source: San Ramon, CA: HIN, Inc., The Health Information Network. 1996. 25 p. Contact: Available from HIN, Inc. 231 Market Place, Number 331, San Ramon, CA 94583. (800) HIN-1121. Fax (925) 358-4377. Website: www.hinbooks.com. PRICE: $36.25 plus shipping per set of 25 booklets; quantity discounts available. Order number 0302. ISBN: 1885274289. Summary: This educational booklet provides information about benign prostatic enlargement, a common enlargement of the prostate gland that affects two out of three men by the time they are 65 years old. Topics covered include the role of the prostate; growth of the prostate; seeing the doctor and what to expect from a prostate examination; deciding about treatment; treatment options; medication; minimally invasive treatments; surgery; and postoperative care. The booklet includes full-color illustrations and a brief glossary of related terms. 7 figures. 2 tables.

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Laser Prostatectomy: For an Enlarged Prostate Source: San Bruno, CA: Krames Communications. 1995. 2 p. Contact: Available from Krames Communications. Order Department, 1100 Grundy Lane, San Bruno, CA 94066. (800) 333-3032. Fax (415) 244-4512. PRICE: $0.40 each (as of 1996); bulk prices available. Summary: This educational brochure describes the use of laser prostatectomy for treating an enlarged prostate. Topics include the symptoms of an enlarged prostate, the risks and complications of laser prostatectomy, preoperative preparation, what to expect during the treatment, postoperative care, healing, when to contact a health care provider, and the anatomy of the prostate. Colorful illustrations depict some of the concepts.

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Benign Prostatic Hyperplasia: A Growing Problem Source: Cambridge, MA: EDAP Technologies, Inc. 199x. 2 p. Contact: Available from EDAP Technomed, Inc. 179 Sidney Street, Cambridge, MA 02139. (800) 933-8868 or (617) 441-9212. PRICE: Single copy free. Summary: This fact sheet briefly reviews the problem of benign prostatic hyperplasia (BPH), a non-cancerous enlargement of the prostate. BPH affects the innermost part of the prostate first, resulting in a gradual squeezing of the urethra. This may cause discomfort and problems in urination and affect quality of life. The fact sheet, written in question and answer format, addresses topics including the anatomy and physiology of the prostate, risk factors for BPH, the symptoms of BPH, diagnostic tests used to confirm BPH, and treatment options. Symptoms of BPH include a weak urinary stream, daytime frequency and urgency, difficulty with urination, and frequent awakening at night to urinate. The fact sheet concludes with a table summarizing the treatments for BPH, including thermotherapy, surgery, medications, and watchful waiting. For each treatment, the fact sheet describes the procedures used, the benefits, and the potential risks. The fact sheet is produced by the manufacturer of one type of equipment used for thermotherapy. (AA-M).

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Prostate Enlargement: Benign Prostatic Hyperplasia Source: Bethesda, MD: National Kidney and Urologic Diseases Information Clearinghouse (NKUDIC), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH). 1998. 12 p. Contact: Available from National Kidney and Urologic Diseases Information Clearinghouse (NKUDIC). 3 Information Way, Bethesda, MD 20892-3580. (800) 891-5390 or (301) 654-4415. Fax (301)634-0716. E-mail: [email protected]. Website: http://www.niddk.nih.gov/health/kidney/nkudic.htm. PRICE: Full-text available online at no charge; single copy free; bulk orders available. Order number: KU-22. Summary: This fact sheet describes benign prostatic hyperplasia (BPH), the enlargement of the prostate gland associated with aging. Though the prostate continues to grow during most of a man's life, the enlargement does not usually cause problems until late in life. As the prostate enlarges, the layer of tissue surrounding it stops it from expanding, causing the gland to press against the urethra, like a clamp on a garden hose. The narrowing of the urethra and partial emptying of the bladder cause many of the problems associated with BPH. The fact sheet describes the theories regarding the cause of BPH, the symptoms, diagnostic tests used to confirm the condition (including the digital rectal exam, the prostate specific antigen, or PSA, blood test, rectal ultrasound, urine flow study, intravenous pyelogram or IVP, and cystoscopy), and treatment options. Treatment options include watchful waiting, which entails monitoring the patient regularly but not undertaking any interventions; drug therapy, including the use of finasteride and the alpha blockers terazosin, doxazosin, and tamsulosin; transurethral microwave procedures (TUMT); transurethral needle ablation (TUNA); and surgical options, including transurethral (TURP), open, or laser surgery. The fact sheet then reviews the postoperative recovery time and what patients can expect during this process. Additional topics covered include postoperative problems with urinating, bleeding, and sexual function after surgery (including erections, ejaculation, and orgasm). The fact sheet encourages men to continue to have a rectal exam once a year, even after surgery. Although some signs of BPH and prostate cancer are the same, having BPH does not seem to increase the chances of getting prostate cancer. Nevertheless, a man who has BPH may have undetected prostate cancer at the same time or may develop prostate cancer in the future. The fact sheet concludes with a brief overview of the current research activities on BPH. Appended to the text are a reading list, a glossary of terms, and a brief description of the National Kidney and Urologic Diseases Information Clearinghouse (NKUDIC). 3 figures. 7 references.

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Prostate, Enlarged (Prostate Hypertrophy; Benign Prostatic Hyperplasia; BPH) Source: in Griffith, H.W. Instructions for Patients. 5th ed. Philadelphia, PA: W.B. Saunders Company. 1994. p. 375. Contact: Available from W.B. Saunders Company. Book Order Fulfillment, 6277 Sea Harbor Drive, Orlando, FL 32887-4430. (800) 545-2522. Fax (800) 874-6418. PRICE: $49.95. ISBN: 0721649300 (English); 0721669972 (Spanish). Summary: This fact sheet on benign prostatic hypertrophy (BPH) is from a compilation of instructions for patients, published in book format. The fact sheet covers a description of the condition, frequent signs and symptoms, causes, risk factors, preventive measures, expected outcome, and possible complications; treatment, including general measures, medication, activity guidelines, and diet; and when to contact one's health care provider. The fact sheet can be photocopied and distributed to patients as a

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reinforcement of oral instructions and as a teaching tool. The book in which the fact sheet appears is available in English or Spanish. •

Living with an Enlarged Prostate Source: Patient Care. 30(3): 36. February 29, 1996. Contact: Available from Medical Economics. 5 Paragon Drive, Montvale, NJ 07645. (800) 432-4570. Fax (201) 573-4956. Summary: This fact sheet provides suggestions for minimizing prostate symptoms in patients with enlarged prostates. Topics include the importance of working closely with a health care provider, drug therapy options, managing symptoms, and surgical treatment options. One sidebar lists recommendations for minimizing prostate symptoms with minor adjustments in lifestyle.

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BPH (Benign Prostatic Hyperplasia) Source: Riviera Beach, FL: AmeriPath, Inc. 2001. 2 p. Contact: Available from AmeriPath, Inc. 7289 Garden Road, Suite 200 Riviera Beach, FL 33404. (800) 330-6565. Email: [email protected]. Website: www.ameripath.com. PRICE: Single copy free; Full-text available online at no charge. Summary: This patient education fact sheet describes benign prostatic hyperplasia (BPH), a noncancerous condition of the prostate characterized by excessive growth (hyperplasia) of tissue. The fact sheet is designed to help patients understand the results that may be obtained from a prostate biopsy. The fact sheet offers background information about BPH, symptoms, risk factors, treatment strategies, and followup of treatment. Treatments reviewed include watchful waiting, surgery, and drug therapy. The fact sheet concludes with a list of recommended questions to ask one's health care provider and a list of web sites for additional information.

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Benign Prostatic Hyperplasia (BPH): A Patient's Guide Source: Baltimore, MD: American Urological Association. 2003. 16 p. Contact: Available from American Urological Association. 1120 North Charles Street, Baltimore, MD 21201. (410) 727-1100. Fax (410) 223-4370. E-mail: [email protected]. Website: www.auanet.org. PRICE: Single copy free; Full-text available online at no charge. Code: BBPHPG. Summary: This patient guide is intended to stimulate and facilitate discussion between the patient and doctor regarding the types of evaluation and treatment for benign prostatic hyperplasia (BPH). The booklet begins with a glossary of terms, then answers common questions about the prostate and BPH. Topics include the causes of the urinary tract symptoms of BPH, how to know when to consult a health care provider, diagnostic tests used to confirm the condition, the use of watchful waiting as a treatment option, how to assess treatment options, the American Urological Association symptom score, medical treatment (drug therapy), minimally invasive treatments, surgical options, the usual symptom relief that can be expected with each treatment option, phytotherapies (plant-based treatments), and how to make a decision about treatment. One chart summarizes each of the BPH treatments available and their risks. 2 figures. 2 tables.

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Prostate Disorders (Enlarged Prostate) at Time of Diagnosis Source: New York, NY: Patient Education Media, Inc. Time Life Medical. 1996. (videocassette). Contact: Available in pharmacies nationwide, or call (800) 588-9959 to find the nearest participating pharmacy. PRICE: $19.95 (suggested, as of 1996). Summary: This videocassette program provides information for patients newly diagnosed with benign prostatic hyperplasia (BPH). The half-hour, newsmagazine style educational program features four sections or 'reports'. The first report examines what is going on inside the body and how the diagnosis was made; computer animation is used to aid viewer understanding. The second report covers what happens after the diagnosis and introduces the viewer to practical issues, including the types of health professionals they may encounter and what lifestyle changes may need to occur. The third report explores options for treatment and management of the condition. The final report addresses issues and answers common questions through the use of an in-studio question-and-answer session. The videotape comes with a personal workbook that includes the program highlights, a glossary, a resource guide, and blank space for readers to record their personal medical journal. (AA-M). 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: •

Prostate Enlargement: Benign Prostatic Hyperplasia Summary: This document gives basic information about the prostate gland and the condition called prostate enlargement, or benign prostatic hyperplasia (BPH). Source: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=831 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 benign prostatic hyperplasia. 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

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

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

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

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

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

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

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

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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 “benign prostatic hyperplasia”. 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 “benign prostatic hyperplasia” (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 “benign prostatic hyperplasia” (or a synonym) into the search box, and click “Submit Query.”

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APPENDIX C. FINDING MEDICAL LIBRARIES Overview In this Appendix, we show you how to quickly find a medical library in your area.

Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.21

Finding a Local Medical Library The quickest method to locate medical libraries is to use the Internet-based directory published by the National Network of Libraries of Medicine (NN/LM). This network includes 4626 members and affiliates that provide many services to librarians, health professionals, and the public. To find a library in your area, simply visit http://nnlm.gov/members/adv.html or call 1-800-338-7657.

Medical Libraries in the U.S. and Canada In addition to the NN/LM, the National Library of Medicine (NLM) lists a number of libraries with reference facilities that are open to the public. The following is the NLM’s list and includes hyperlinks to each library’s Web site. These Web pages can provide information on hours of operation and other restrictions. The list below is a small sample of

21

Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.

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libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)22: •

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

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

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

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

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

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

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California: Gateway Health Library (Sutter Gould Medical Foundation)

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

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

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

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

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

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

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

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

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

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

•

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

22

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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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

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

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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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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•

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

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

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

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

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

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

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

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

•

Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html

•

On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/

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Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp

•

Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm

Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a). The NIH suggests the following Web sites in the ADAM Medical Encyclopedia when searching for information on benign prostatic hyperplasia: •

Basic Guidelines for Benign Prostatic Hyperplasia Benign prostatic hyperplasia Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000381.htm BPH Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000381.htm

•

Signs & Symptoms for Benign Prostatic Hyperplasia Blood in the urine Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003138.htm Bloody urine Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003138.htm Difficulty urinating Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003143.htm

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High blood pressure Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003082.htm Hyperthermia Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003090.htm Impotence Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003164.htm Incontinence Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003142.htm Increased urinary frequency Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003140.htm Nocturia Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003141.htm Pain with urination Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003145.htm Urinary hesitancy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003143.htm Urinary urgency Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003140.htm •

Diagnostics and Tests for Benign Prostatic Hyperplasia BP Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003398.htm Cystoscopy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003903.htm Digital rectal exam Web site: http://www.nlm.nih.gov/medlineplus/ency/article/007069.htm IVP Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003782.htm PSA Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003346.htm Urinalysis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003579.htm Urine culture Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003751.htm Voiding cystourethrogram Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003784.htm

Online Glossaries 241

X-ray Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003337.htm •

Surgery and Procedures for Benign Prostatic Hyperplasia Open prostatectomy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002996.htm Prostatectomy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002996.htm Transurethral resection of the prostate Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002996.htm TUIP Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002996.htm TURP Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002996.htm

•

Background Topics for Benign Prostatic Hyperplasia Acute Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002215.htm Antigen Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002224.htm Benign Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002236.htm Bleeding Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000045.htm Hormone levels Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003445.htm Incidence Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002387.htm Scrotum Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002296.htm Stents Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002303.htm Support group - BPH Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003977.htm Testicles Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002334.htm

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Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •

Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical

•

MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html

•

Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/

•

Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine

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BENIGN PROSTATIC HYPERPLASIA DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 5-alpha: Enzyme converting testosterone to dihydrotestosterone. [NIH] Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] Ablation: The removal of an organ by surgery. [NIH] Acanthosis Nigricans: A circumscribed melanosis consisting of a brown-pigmented, velvety verrucosity or fine papillomatosis appearing in the axillae and other body folds. It occurs in association with endocrine disorders, underlying malignancy, administration of certain drugs, or as in inherited disorder. [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] Acne: A disorder of the skin marked by inflammation of oil glands and hair glands. [NIH] Acne Vulgaris: A chronic disorder of the pilosebaceous apparatus associated with an increase in sebum secretion. It is characterized by open comedones (blackheads), closed comedones (whiteheads), and pustular nodules. The cause is unknown, but heredity and age are predisposing factors. [NIH] Acute renal: A condition in which the kidneys suddenly stop working. In most cases, kidneys can recover from almost complete loss of function. [NIH] Acyl: Chemical signal used by bacteria to communicate. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adaptation: 1. The adjustment of an organism to its environment, or the process by which it enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the intensity of light; the adjustment to such variations. 3. The decline in the frequency of firing of a neuron, particularly of a receptor, under conditions of constant stimulation. 4. In dentistry, (a) the proper fitting of a denture, (b) the degree of proximity and interlocking of restorative material to a tooth preparation, (c) the exact adjustment of bands to teeth. 5. In microbiology, the adjustment of bacterial physiology to a new environment. [EU] Adenine: A purine base and a fundamental unit of adenine nucleotides. [NIH] Adenocarcinoma: A malignant epithelial tumor with a glandular organization. [NIH]

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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] Adenosine Monophosphate: Adenylic acid. Adenine nucleotide containing one phosphate group esterified to the sugar moiety in the 2'-, 3'-, or 5'-position. [NIH] Adenosine Triphosphate: Adenosine 5'-(tetrahydrogen triphosphate). An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter. [NIH] Adenylate Cyclase: An enzyme of the lyase class that catalyzes the formation of cyclic AMP and pyrophosphate from ATP. EC 4.6.1.1. [NIH] Adipocytes: Fat-storing cells found mostly in the abdominal cavity and subcutaneous tissue. Fat is usually stored in the form of tryglycerides. [NIH] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH] Adrenal Medulla: The inner part of the adrenal gland; it synthesizes, stores and releases catecholamines. [NIH] Adrenaline: A hormone. Also called epinephrine. [NIH] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adrenergic Antagonists: Drugs that bind to but do not activate adrenergic receptors. Adrenergic antagonists block the actions of the endogenous adrenergic transmitters epinephrine and norepinephrine. [NIH] Adrenoreceptor: Receptors specifically sensitive to and operated by adrenaline and/or noradrenaline and related sympathomimetic drugs. Adrenoreceptor is an alternative name. [NIH]

Adverse Effect: An unwanted side effect of treatment. [NIH] 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] Age Groups: Persons classified by age from birth (infant, newborn) to octogenarians and older (aged, 80 and over). [NIH] Aged, 80 and Over: A person 80 years of age and older. [NIH]

Dictionary 245

Ageing: A physiological or morphological change in the life of an organism or its parts, generally irreversible and typically associated with a decline in growth and reproductive vigor. [NIH] Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] 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] Allergen: An antigenic substance capable of producing immediate-type hypersensitivity (allergy). [EU] Allylestrenol: A synthetic steroid with progestational activity. [NIH] Alopecia: Absence of hair from areas where it is normally present. [NIH] Alpha Particles: Positively charged particles composed of two protons and two neutrons, i.e., helium nuclei, emitted during disintegration of very heavy isotopes; a beam of alpha particles or an alpha ray has very strong ionizing power, but weak penetrability. [NIH] Alpha-1: A protein with the property of inactivating proteolytic enzymes such as leucocyte collagenase and elastase. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Ameliorating: A changeable condition which prevents the consequence of a failure or accident from becoming as bad as it otherwise would. [NIH] Amenorrhea: Absence of menstruation. [NIH] Amine: An organic compound containing nitrogen; any member of a group of chemical compounds formed from ammonia by replacement of one or more of the hydrogen atoms by organic (hydrocarbon) radicals. The amines are distinguished as primary, secondary, and tertiary, according to whether one, two, or three hydrogen atoms are replaced. The amines include allylamine, amylamine, ethylamine, methylamine, phenylamine, propylamine, and many other compounds. [EU] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino 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] Aminopeptidases: A subclass of exopeptidases that act on the free N terminus end of a polypeptide liberating a single amino acid residue. EC 3.4.11. [NIH]

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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] Ampulla: A sac-like enlargement of a canal or duct. [NIH] Amputation: Surgery to remove part or all of a limb or appendage. [NIH] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anaesthetic: 1. Pertaining to, characterized by, or producing anaesthesia. 2. A drug or agent that is used to abolish the sensation of pain. [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] 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] 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] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Anesthetics: Agents that are capable of inducing a total or partial loss of sensation, especially tactile sensation and pain. They may act to induce general anesthesia, in which an unconscious state is achieved, or may act locally to induce numbness or lack of sensation at a targeted site. [NIH] Angiotensinogen: An alpha-globulin of which a fragment of 14 amino acids is converted by renin to angiotensin I, the inactive precursor of angiotensin II. It is a member of the serpin superfamily. [NIH] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anionic: Pertaining to or containing an anion. [EU] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Anoikis: Apoptosis triggered by loss of contact with the extracellular matrix. [NIH] Anomalies: Birth defects; abnormalities. [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

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supplies) or to production of a specific antibiotic substance (e. g. penicillin). [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] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Antidiuretic: Suppressing the rate of urine formation. [EU] Antidote: A remedy for counteracting a poison. [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] Antihypertensive: An agent that reduces high blood pressure. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are highly reactive chemicals that often contain oxygen. They are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation. [NIH] 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] 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

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presented or with minor modifications. [NIH] Approximate: Approximal [EU] Aqueous: Having to do with water. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Argipressin: Cys-Tyr-Phe-Gln-Asn-Cys-Pro-Arg-Gly-NH2, cyclic 1-6 disulfide. The usual mammalian antidiuretic hormone, it is a cyclic nonapeptide with arginine in position 8 of the chain. Argipressin is used to treat diabetes insipidus and as hemostatic because of its vasoconstrictor action. [NIH] Aromatase: An enzyme which converts androgens to estrogens by desaturating ring A of the steroid. This enzyme complex is located in the endoplasmic reticulum of estrogenproducing cells including ovaries, placenta, testicular Sertoli and Leydig cells, adipose, and brain tissues. The enzyme complex has two components, one of which is the CYP19 gene product, the aromatase cytochrome P-450. The other component is NADPH-cytochrome P450 reductase which transfers reducing equivalents to P-450(arom). EC 1.14.13.-. [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] Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH] Artificial Intelligence: The study and implementation of techniques and methods for designing computer systems to perform functions normally associated with human intelligence, such as understanding language, learning, reasoning, problem solving, etc. [NIH]

Aseptic: Free from infection or septic material; sterile. [EU] 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] Astrocytes: The largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the blood brain barrier. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with microglia) respond to injury. Astrocytes have high- affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitter, but their role in signaling (as in many other functions) is not well understood. [NIH] Astrocytoma: A tumor that begins in the brain or spinal cord in small, star-shaped cells called astrocytes. [NIH] Asymptomatic: Having no signs or symptoms of disease. [NIH] Atresia: Lack of a normal opening from the esophagus, intestines, or anus. [NIH] Atrial: Pertaining to an atrium. [EU] Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] Atropine: A toxic alkaloid, originally from Atropa belladonna, but found in other plants,

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mainly Solanaceae. [NIH] Autonomic Nervous System: The enteric, parasympathetic, and sympathetic nervous systems taken together. Generally speaking, the autonomic nervous system regulates the internal environment during both peaceful activity and physical or emotional stress. Autonomic activity is controlled and integrated by the central nervous system, especially the hypothalamus and the solitary nucleus, which receive information relayed from visceral afferents; these and related central and sensory structures are sometimes (but not here) considered to be part of the autonomic nervous system itself. [NIH] Axons: Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bactericidal: Substance lethal to bacteria; substance capable of killing bacteria. [NIH] Bacteriuria: The presence of bacteria in the urine with or without consequent urinary tract infection. Since bacteriuria is a clinical entity, the term does not preclude the use of urine/microbiology for technical discussions on the isolation and segregation of bacteria in the urine. [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] Basal cells: Small, round cells found in the lower part (or base) of the epidermis, the outer layer of the skin. [NIH] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Basement Membrane: Ubiquitous supportive tissue adjacent to epithelium and around smooth and striated muscle cells. This tissue contains intrinsic macromolecular components such as collagen, laminin, and sulfated proteoglycans. As seen by light microscopy one of its subdivisions is the basal (basement) lamina. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]

Benign prostatic hyperplasia: A benign (noncancerous) condition in which an overgrowth of prostate tissue pushes against the urethra and the bladder, blocking the flow of urine. Also called benign prostatic hypertrophy or BPH. [NIH] Benign tumor: A noncancerous growth that does not invade nearby tissue or spread to other parts of the body. [NIH] Beta-Galactosidase: A group of enzymes that catalyzes the hydrolysis of terminal, nonreducing beta-D-galactose residues in beta-galactosides. Deficiency of beta-Galactosidase A1 may cause gangliodisosis GM1. EC 3.2.1.23. [NIH]

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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] Biliary Tract: The gallbladder and its ducts. [NIH] Binding Sites: The reactive parts of a macromolecule that directly participate in its specific combination with another molecule. [NIH] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biofilms: Films of bacteria or other microbial organisms, usually embedded in extracellular polymers such as implanted medical devices, which adhere to surfaces submerged in, or subjected to, aquatic environments (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed). Biofilms consist of multilayers of microbial cells glued together to form microbial communities which are highly resistant to both phagocytes and antibiotics. [NIH] Biological therapy: Treatment to stimulate or restore the ability of the immune system to fight infection and disease. Also used to lessen side effects that may be caused by some cancer treatments. Also known as immunotherapy, biotherapy, or biological response modifier (BRM) therapy. [NIH] 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] Biopsy specimen: Tissue removed from the body and examined under a microscope to determine whether disease is present. [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 clearance. [NIH] Bladder: The organ that stores urine. [NIH]

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Bladder Calculi: Calculi of the urinary bladder; also known as vesical calculi or bladder stones, and cystoliths. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood transfusion: The administration of blood or blood products into a blood vessel. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blot: To transfer DNA, RNA, or proteins to an immobilizing matrix such as nitrocellulose. [NIH]

Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blotting and transferred to strips of nitrocellulose paper. The blots are then detected by radiolabeled antibody probes. [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 Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone metastases: Cancer that has spread from the original (primary) tumor to the bone. [NIH]

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] Breast Self-Examination: The inspection of one's breasts, usually for signs of disease, especially neoplastic disease. [NIH] Bronchi: The larger air passages of the lungs arising from the terminal bifurcation of the trachea. [NIH] Bronchial: Pertaining to one or more bronchi. [EU] Bronchodilator: A drug that relaxes the smooth muscles in the constricted airway. [NIH] Bulbar: Pertaining to a bulb; pertaining to or involving the medulla oblongata, as bulbar paralysis. [EU] Bypass: A surgical procedure in which the doctor creates a new pathway for the flow of body fluids. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Calculi: An abnormal concretion occurring mostly in the urinary and biliary tracts, usually composed of mineral salts. Also called stones. [NIH]

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Callus: A callosity or hard, thick skin; the bone-like reparative substance that is formed round the edges and fragments of broken bone. [NIH] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Carbohydrates: The largest class of organic compounds, including starches, glycogens, cellulose, gums, and simple sugars. Carbohydrates are composed of carbon, hydrogen, and oxygen in a ratio of Cn(H2O)n. [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] 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 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] Case-Control Studies: Studies which start with the identification of persons with a disease of interest and a control (comparison, referent) group without the disease. The relationship of an attribute to the disease is examined by comparing diseased and non-diseased persons with regard to the frequency or levels of the attribute in each group. [NIH] Caspase: Enzyme released by the cell at a crucial stage in apoptosis in order to shred all cellular proteins. [NIH] Castration: Surgical removal or artificial destruction of gonads. [NIH] Cataract: An opacity, partial or complete, of one or both eyes, on or in the lens or capsule, especially an opacity impairing vision or causing blindness. The many kinds of cataract are classified by their morphology (size, shape, location) or etiology (cause and time of occurrence). [EU] 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 can also be man-made. [NIH] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [NIH] Catheter: A flexible tube used to deliver fluids into or withdraw fluids from the body. [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] Caudal: Denoting a position more toward the cauda, or tail, than some specified point of reference; same as inferior, in human anatomy. [EU]

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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 Adhesion: Adherence of cells to surfaces or to other cells. [NIH] Cell Cycle: The complex series of phenomena, occurring between the end of one cell division and the end of the next, by which cellular material is divided between daughter cells. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell Lineage: The developmental history of cells as traced from the first division of the original cell or cells in the embryo. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Size: The physical dimensions of a cell. It refers mainly to changes in dimensions correlated with physiological or pathological changes in cells. [NIH] Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Central Nervous System Infections: Pathogenic infections of the brain, spinal cord, and meninges. DNA virus infections; RNA virus infections; bacterial infections; mycoplasma infections; Spirochaetales infections; fungal infections; protozoan infections; helminthiasis; and prion diseases may involve the central nervous system as a primary or secondary process. [NIH] Ceramide: A type of fat produced in the body. It may cause some types of cells to die, and is being studied in cancer treatment. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral hemispheres: The two halves of the cerebrum, the part of the brain that controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. The right hemisphere controls muscle movement on the left side of the body, and the left hemisphere controls muscle movement on the right side of the body. [NIH] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cervix: The lower, narrow end of the uterus that forms a canal between the uterus and vagina. [NIH]

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Chemopreventive: Natural or synthetic compound used to intervene in the early precancerous stages of carcinogenesis. [NIH] Chemotherapeutic agent: A drug used to treat cancer. [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] Cholinergic: Resembling acetylcholine in pharmacological action; stimulated by or releasing acetylcholine or a related compound. [EU] Chondrocytes: Polymorphic cells that form cartilage. [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 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] Chymotrypsin: A serine endopeptidase secreted by the pancreas as its zymogen, chymotrypsinogen and carried in the pancreatic juice to the duodenum where it is activated by trypsin. It selectively cleaves aromatic amino acids on the carboxyl side. [NIH] Circumcision: Excision of the prepuce or part of it. [NIH] CIS: Cancer Information Service. The CIS is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER, or by using the Web site at http://cis.nci.nih.gov. [NIH] Clamp: A u-shaped steel rod used with a pin or wire for skeletal traction in the treatment of certain fractures. [NIH] 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] Cleave: A double-stranded cut in DNA with a restriction endonuclease. [NIH] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]

Clinical series: A case series in which the patients receive treatment in a clinic or other medical facility. [NIH] Clinical study: A research study in which patients receive treatment in a clinic or other medical facility. Reports of clinical studies can contain results for single patients (case reports) or many patients (case series or clinical trials). [NIH] Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA

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molecules. [NIH] Coagulation: 1. The process of clot formation. 2. In colloid chemistry, the solidification of a sol into a gelatinous mass; an alteration of a disperse phase or of a dissolved solid which causes the separation of the system into a liquid phase and an insoluble mass called the clot or curd. Coagulation is usually irreversible. 3. In surgery, the disruption of tissue by physical means to form an amorphous residuum, as in electrocoagulation and photocoagulation. [EU] Coculture: The culturing of normal cells or tissues with infected or latently infected cells or tissues of the same kind (From Dorland, 28th ed, entry for cocultivation). It also includes culturing of normal cells or tissues with other normal cells or tissues. [NIH] Coenzyme: An organic nonprotein molecule, frequently a phosphorylated derivative of a water-soluble vitamin, that binds with the protein molecule (apoenzyme) to form the active enzyme (holoenzyme). [EU] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Cohort Studies: Studies in which subsets of a defined population are identified. These groups may or may not be exposed to factors hypothesized to influence the probability of the occurrence of a particular disease or other outcome. Cohorts are defined populations which, as a whole, are followed in an attempt to determine distinguishing subgroup characteristics. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Colloidal: Of the nature of a colloid. [EU] Colon: The long, coiled, tubelike organ that removes water from digested food. The remaining material, solid waste called stool, moves through the colon to the rectum and leaves the body through the anus. [NIH] Colorectal: Having to do with the colon or the rectum. [NIH] Combination Therapy: Association of 3 drugs to treat AIDS (AZT + DDC or DDI + protease inhibitor). [NIH] Combinatorial: A cut-and-paste process that churns out thousands of potentially valuable compounds at once. [NIH] Comorbidity: The presence of co-existing or additional diseases with reference to an initial diagnosis or with reference to the index condition that is the subject of study. Comorbidity may affect the ability of affected individuals to function and also their survival; it may be used as a prognostic indicator for length of hospital stay, cost factors, and outcome or survival. [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols

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C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complete remission: The disappearance of all signs of cancer. Also called a complete response. [NIH] Compliance: Distensibility measure of a chamber such as the lungs (lung compliance) or bladder. Compliance is expressed as a change in volume per unit change in pressure. [NIH] Computational Biology: A field of biology concerned with the development of techniques 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] Computer Simulation: Computer-based representation of physical systems and phenomena such as chemical processes. [NIH] Computer Systems: Systems composed of a computer or computers, peripheral equipment, such as disks, printers, and terminals, and telecommunications capabilities. [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] Concretion: Minute, hard, yellow masses found in the palpebral conjunctivae of elderly people or following chronic conjunctivitis, composed of the products of cellular degeneration retained in the depressions and tubular recesses in the conjunctiva. [NIH] Conduction: The transfer of sound waves, heat, nervous impulses, or electricity. [EU] Confusion: A mental state characterized by bewilderment, emotional disturbance, lack of clear thinking, and perceptual disorientation. [NIH]

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Congestion: Excessive or abnormal accumulation of blood in a part. [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] Connective Tissue Cells: A group of cells that includes fibroblasts, cartilage cells, adipocytes, smooth muscle cells, and bone cells. [NIH] Constrict: Tighten; narrow. [NIH] Constriction: The act of constricting. [NIH] Consultation: A deliberation between two or more physicians concerning the diagnosis and the proper method of treatment in a case. [NIH] Contraceptive: An agent that diminishes the likelihood of or prevents conception. [EU] Contractility: Capacity for becoming short in response to a suitable stimulus. [EU] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Control group: In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works. [NIH] Controlled clinical trial: A clinical study that includes a comparison (control) group. The comparison group receives a placebo, another treatment, or no treatment at all. [NIH] Controlled study: An experiment or clinical trial that includes a comparison (control) group. [NIH]

Convulsions: A general term referring to sudden and often violent motor activity of cerebral or brainstem origin. Convulsions may also occur in the absence of an electrical cerebral discharge (e.g., in response to hypotension). [NIH] Cooperative group: A group of physicians, hospitals, or both formed to treat a large number of persons in the same way so that new treatment can be evaluated quickly. Clinical trials of new cancer treatments often require many more people than a single physician or hospital can care for. [NIH] Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary heart disease: A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Corpus: The body of the uterus. [NIH] Corpus Luteum: The yellow glandular mass formed in the ovary by an ovarian follicle that has ruptured and discharged its ovum. [NIH] Corrosion: Irreversible destruction of skin tissue. [NIH]

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Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Craniocerebral Trauma: Traumatic injuries involving the cranium and intracranial structures (i.e., brain; cranial nerves; meninges; and other structures). Injuries may be classified by whether or not the skull is penetrated (i.e., penetrating vs. nonpenetrating) or whether there is an associated hemorrhage. [NIH] Creatinine: A compound that is excreted from the body in urine. Creatinine levels are measured to monitor kidney function. [NIH] Crossing-over: The exchange of corresponding segments between chromatids of homologous chromosomes during meiosia, forming a chiasma. [NIH] Cross-Sectional Studies: Studies in which the presence or absence of disease or other health-related variables are determined in each member of the study population or in a representative sample at one particular time. This contrasts with longitudinal studies which are followed over a period of time. [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] 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] 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] Cyproterone Acetate: An agent with anti-androgen and progestational properties. It shows competitive binding with dihydrotestosterone at androgen receptor sites. [NIH] Cyst: A sac or capsule filled with fluid. [NIH] Cystectomy: Used for excision of the urinary bladder. [NIH] Cystine: A covalently linked dimeric nonessential amino acid formed by the oxidation of cysteine. Two molecules of cysteine are joined together by a disulfide bridge to form cystine. [NIH]

Cystitis: Inflammation of the urinary bladder. [EU] Cystoscope: A thin, lighted instrument used to look inside the bladder and remove tissue samples or small tumors. [NIH] Cystoscopy: Endoscopic examination, therapy or surgery of the urinary bladder. [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

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and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, . New cytochromes are named according to the wavelength in nanometres of the absorption maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. [NIH] Cytotoxic: Cell-killing. [NIH] Cytotoxic chemotherapy: Anticancer drugs that kill cells, especially cancer cells. [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] Decarboxylation: The removal of a carboxyl group, usually in the form of carbon dioxide, from a chemical compound. [NIH] Decompensation: Failure of compensation; cardiac decompensation is marked by dyspnea, venous engorgement, and edema. [EU] Decongestant: An agent that reduces congestion or swelling. [EU] Decubitus: An act of lying down; also the position assumed in lying down. [EU] Defense Mechanisms: Unconscious process used by an individual or a group of individuals in order to cope with impulses, feelings or ideas which are not acceptable at their conscious level; various types include reaction formation, projection and self reversal. [NIH] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Depolarization: The process or act of neutralizing polarity. In neurophysiology, the reversal of the resting potential in excitable cell membranes when stimulated, i.e., the tendency of the cell membrane potential to become positive with respect to the potential outside the cell. [EU] 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] Desmopressin: A synthetic analog of the natural hormone 8-arginine vasopressin (argipressin). Its action is mediated by the vasopressin receptor V2. It has prolonged antidiuretic activity, but little pressor effects. It also modulates levels of circulating factor VIII and von Willebrand factor. [NIH] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] Developmental Biology: The field of biology which deals with the process of the growth and differentiation of an organism. [NIH] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in

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common. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diastolic: Of or pertaining to the diastole. [EU] Diathermy: The induction of local hyperthermia by either short radio waves or highfrequency sound waves. [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] 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] 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] Dimerization: The process by which two molecules of the same chemical composition form a condensation product or polymer. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Discrete: Made up of separate parts or characterized by lesions which do not become blended; not running together; separate. [NIH] Discrimination: The act of qualitative and/or quantitative differentiation between two or more stimuli. [NIH] Disease Progression: The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis. [NIH] Disease Susceptibility: A constitution or condition of the body which makes the tissues react in special ways to certain extrinsic stimuli and thus tends to make the individual more than usually susceptible to certain diseases. [NIH] Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [EU] Dissection: Cutting up of an organism for study. [NIH] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Dizziness: An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. [NIH] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several

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systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] Dorsal: 1. Pertaining to the back or to any dorsum. 2. Denoting a position more toward the back surface than some other object of reference; same as posterior in human anatomy; superior in the anatomy of quadrupeds. [EU] Dorsum: A plate of bone which forms the posterior boundary of the sella turcica. [NIH] 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 delayed or long-acting drug effect. They include capsules, liniments, ointments, pharmaceutical solutions, powders, tablets, etc. [NIH] Dosimetry: All the methods either of measuring directly, or of measuring indirectly and computing, absorbed dose, absorbed dose rate, exposure, exposure rate, dose equivalent, and the science associated with these methods. [NIH] Double-blind: Pertaining to a clinical trial or other experiment in which neither the subject nor the person administering treatment knows which treatment any particular subject is receiving. [EU] Doxazosin: A selective alpha-1-adrenergic blocker that lowers serum cholesterol. It is also effective in the treatment of hypertension. [NIH] Drive: A state of internal activity of an organism that is a necessary condition before a given stimulus will elicit a class of responses; e.g., a certain level of hunger (drive) must be present before food will elicit an eating response. [NIH] Drug 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] Dysmenorrhea: Painful menstruation. [NIH] Dyspnea: Difficult or labored breathing. [NIH] Dysuria: Painful or difficult urination. [EU] Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [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] Ejaculation: The release of semen through the penis during orgasm. [NIH] Elastin: The protein that gives flexibility to tissues. [NIH]

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Electrocoagulation: Electrosurgical procedures used to treat hemorrhage (e.g., bleeding ulcers) and to ablate tumors, mucosal lesions, and refractory arrhythmias. [NIH] Electrode: Component of the pacing system which is at the distal end of the lead. It is the interface with living cardiac tissue across which the stimulus is transmitted. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] Electrophoresis: An electrochemical process in which macromolecules or colloidal particles with a net electric charge migrate in a solution under the influence of an electric current. [NIH]

Electroplating: Coating with a metal or alloy by electrolysis. [NIH] Electroporation: A technique in which electric pulses of intensity in kilovolts per centimeter and of microsecond-to-millisecond duration cause a temporary loss of the semipermeability of cell membranes, thus leading to ion leakage, escape of metabolites, and increased uptake by cells of drugs, molecular probes, and DNA. Some applications of electroporation include introduction of plasmids or foreign DNA into living cells for transfection, fusion of cells to prepare hybridomas, and insertion of proteins into cell membranes. [NIH] Emboli: Bit of foreign matter which enters the blood stream at one point and is carried until it is lodged or impacted in an artery and obstructs it. It may be a blood clot, an air bubble, fat or other tissue, or clumps of bacteria. [NIH] Embolization: The blocking of an artery by a clot or foreign material. Embolization can be done as treatment to block the flow of blood to a tumor. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Embryology: The study of the development of an organism during the embryonic and fetal stages of life. [NIH] Endocrine System: The system of glands that release their secretions (hormones) directly into the circulatory system. In addition to the endocrine glands, included are the chromaffin system and the neurosecretory systems. [NIH] Endocrinology: A subspecialty of internal medicine concerned with the metabolism, physiology, and disorders of the endocrine system. [NIH] Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [NIH] 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] Endorphins: One of the three major groups of endogenous opioid peptides. They are large peptides derived from the pro-opiomelanocortin precursor. The known members of this group are alpha-, beta-, and gamma-endorphin. The term endorphin is also sometimes used to refer to all opioid peptides, but the narrower sense is used here; opioid peptides is used

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for the broader group. [NIH] Endoscope: A thin, lighted tube used to look at tissues inside the body. [NIH] Endoscopic: A technique where a lateral-view endoscope is passed orally to the duodenum for visualization of the ampulla of Vater. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endotoxin: Toxin from cell walls of bacteria. [NIH] End-stage renal: Total chronic kidney failure. When the kidneys fail, the body retains fluid and harmful wastes build up. A person with ESRD needs treatment to replace the work of the failed kidneys. [NIH] Energy balance: Energy is the capacity of a body or a physical system for doing work. Energy balance is the state in which the total energy intake equals total energy needs. [NIH] Enkephalins: One of the three major families of endogenous opioid peptides. The enkephalins are pentapeptides that are widespread in the central and peripheral nervous systems and in the adrenal medulla. [NIH] Enucleation: Removal of the nucleus from an eucaryiotic cell. [NIH] Enuresis: Involuntary discharge of urine after the age at which urinary control should have been achieved; often used alone with specific reference to involuntary discharge of urine occurring during sleep at night (bed-wetting, nocturnal enuresis). [EU] 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] Epidemiologic Studies: Studies designed to examine associations, commonly, hypothesized causal relations. They are usually concerned with identifying or measuring the effects of risk factors or exposures. The common types of analytic study are case-control studies, cohort studies, and cross-sectional studies. [NIH] Epidermal: Pertaining to or resembling epidermis. Called also epidermic or epidermoid. [EU] Epidermal Growth Factor: A 6 kD polypeptide growth factor initially discovered in mouse submaxillary glands. Human epidermal growth factor was originally isolated from urine based on its ability to inhibit gastric secretion and called urogastrone. epidermal growth factor exerts a wide variety of biological effects including the promotion of proliferation and differentiation of mesenchymal and epithelial cells. [NIH] Epidermal growth factor receptor: EGFR. The protein found on the surface of some cells and to which epidermal growth factor binds, causing the cells to divide. It is found at abnormally high levels on the surface of many types of cancer cells, so these cells may divide excessively in the presence of epidermal growth factor. Also known as ErbB1 or HER1. [NIH] Epidermis: Nonvascular layer of the skin. It is made up, from within outward, of five layers: 1) basal layer (stratum basale epidermidis); 2) spinous layer (stratum spinosum epidermidis); 3) granular layer (stratum granulosum epidermidis); 4) clear layer (stratum lucidum epidermidis); and 5) horny layer (stratum corneum epidermidis). [NIH] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local

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anesthetics. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Equipment and Supplies: Expendable and nonexpendable equipment, supplies, apparatus, and instruments that are used in diagnostic, surgical, therapeutic, scientific, and experimental procedures. [NIH] Erectile: The inability to get or maintain an erection for satisfactory sexual intercourse. Also called impotence. [NIH] Erection: The condition of being made rigid and elevated; as erectile tissue when filled with blood. [EU] 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] Estrogen: One of the two female sex hormones. [NIH] Estrogen receptor: ER. Protein found on some cancer cells to which estrogen will attach. [NIH]

Ethanol: A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. [NIH] Ethnic Groups: A group of people with a common cultural heritage that sets them apart from others in a variety of social relationships. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Evoke: The electric response recorded from the cerebral cortex after stimulation of a peripheral sense organ. [NIH] Excitability: Property of a cardiac cell whereby, when the cell is depolarized to a critical level (called threshold), the membrane becomes permeable and a regenerative inward current causes an action potential. [NIH] Excitation: An act of irritation or stimulation or of responding to a stimulus; the addition of energy, as the excitation of a molecule by absorption of photons. [EU] Excrete: To get rid of waste from the body. [NIH] Exhaustion: The feeling of weariness of mind and body. [NIH] Exocrine: Secreting outwardly, via a duct. [EU] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Exopeptidases: A sub-subclass of peptide hydrolases that act only near the ends of polypeptide chains. Exopeptidases are further divided into aminopeptidases, EC 3.4.11; dipeptidases, EC 3.4.13; dipeptidyl peptidases & tripeptidyl peptidases, EC 3.4.14; peptidyldipeptidases, EC 3.4.15; carboxypeptidases, EC 3.4.16 - EC 3.4.18, and omega peptidases, EC 3.4.19. EC 3.4.-. [NIH]

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Expiration: The act of breathing out, or expelling air from the lungs. [EU] External-beam radiation: Radiation therapy that uses a machine to aim high-energy rays at the cancer. Also called external radiation. [NIH] Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] Extracorporeal: Situated or occurring outside the body. [EU] Facial: Of or pertaining to the face. [EU] Fallopian tube: The oviduct, a muscular tube about 10 cm long, lying in the upper border of the broad ligament. [NIH] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]

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] Fibroblast Growth Factor: Peptide isolated from the pituitary gland and from the brain. It is a potent mitogen which stimulates growth of a variety of mesodermal cells including chondrocytes, granulosa, and endothelial cells. The peptide may be active in wound healing and animal limb regeneration. [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Finasteride: An orally active testosterone 5-alpha-reductase inhibitor. It is used as a surgical alternative for treatment of benign prostatic hyperplasia. [NIH] Fine-needle aspiration: The removal of tissue or fluid with a needle for examination under a microscope. Also called needle biopsy. [NIH] Fistula: Abnormal communication most commonly seen between two internal organs, or between an internal organ and the surface of the body. [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

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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] Flatus: Gas passed through the rectum. [NIH] Flow Cytometry: Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake. [NIH] Fluorescence: The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis. [NIH] Fluorescent Dyes: Dyes that emit light when exposed to light. The wave length of the emitted light is usually longer than that of the incident light. Fluorochromes are substances that cause fluorescence in other substances, i.e., dyes used to mark or label other compounds with fluorescent tags. They are used as markers in biochemistry and immunology. [NIH] Flutamide: An antiandrogen with about the same potency as cyproterone in rodent and canine species. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Fractionation: Dividing the total dose of radiation therapy into several smaller, equal doses delivered over a period of several days. [NIH] Free Radicals: Highly reactive molecules with an unsatisfied electron valence pair. Free radicals are produced in both normal and pathological processes. They are proven or suspected agents of tissue damage in a wide variety of circumstances including radiation, damage from environment chemicals, and aging. Natural and pharmacological prevention of free radical damage is being actively investigated. [NIH] Fungus: A general term used to denote a group of eukaryotic protists, including mushrooms, yeasts, rusts, moulds, smuts, etc., which are characterized by the absence of chlorophyll and by the presence of a rigid cell wall composed of chitin, mannans, and sometimes cellulose. They are usually of simple morphological form or show some reversible cellular specialization, such as the formation of pseudoparenchymatous tissue in the fruiting body of a mushroom. The dimorphic fungi grow, according to environmental conditions, as moulds or yeasts. [EU] Galactosides: Glycosides formed by the reaction of the hydroxyl group on the anomeric carbon atom of galactose with an alcohol to form an acetal. They include both alpha- and beta-galactosides. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH]

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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] Ganglioside: Protein kinase C's inhibitor which reduces ischemia-related brain damage. [NIH]

Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gastric: Having to do with the stomach. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]

Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]

Gene Deletion: A genetic rearrangement through loss of segments of DNA or RNA, bringing sequences which are normally separated into close proximity. This deletion may be detected using cytogenetic techniques and can also be inferred from the phenotype, indicating a deletion at one specific locus. [NIH] Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Gene Expression Profiling: The determination of the pattern of genes expressed i.e., transcribed, under specific circumstances or in a specific cell. [NIH] Gene Therapy: The introduction of new genes into cells for the purpose of treating disease by restoring or adding gene expression. Techniques include insertion of retroviral vectors, transfection, homologous recombination, and injection of new genes into the nuclei of single cell embryos. The entire gene therapy process may consist of multiple steps. The new genes may be introduced into proliferating cells in vivo (e.g., bone marrow) or in vitro (e.g., fibroblast cultures) and the modified cells transferred to the site where the gene expression is required. Gene therapy may be particularly useful for treating enzyme deficiency diseases, hemoglobinopathies, and leukemias and may also prove useful in restoring drug sensitivity, particularly for leukemia. [NIH] 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] Generator: Any system incorporating a fixed parent radionuclide from which is produced a daughter radionuclide which is to be removed by elution or by any other method and used in a radiopharmaceutical. [NIH] Genetic Code: The specifications for how information, stored in nucleic acid sequence (base sequence), is translated into protein sequence (amino acid sequence). The start, stop, and order of amino acids of a protein is specified by consecutive triplets of nucleotides called codons (codon). [NIH] Genetic Engineering: Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc. [NIH] Genetic Markers: A phenotypically recognizable genetic trait which can be used to identify

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a genetic locus, a linkage group, or a recombination event. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genital: Pertaining to the genitalia. [EU] Genitourinary: Pertaining to the genital and urinary organs; urogenital; urinosexual. [EU] Genitourinary system: The parts of the body that play a role in reproduction, getting rid of waste products in the form of urine, or both. [NIH] Genomics: The systematic study of the complete DNA sequences (genome) of organisms. [NIH]

Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Geriatric: Pertaining to the treatment of the aged. [EU] Germ Cells: The reproductive cells in multicellular organisms. [NIH] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] 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] Glioblastoma: A malignant form of astrocytoma histologically characterized by pleomorphism of cells, nuclear atypia, microhemorrhage, and necrosis. They may arise in any region of the central nervous system, with a predilection for the cerebral hemispheres, basal ganglia, and commissural pathways. Clinical presentation most frequently occurs in the fifth or sixth decade of life with focal neurologic signs or seizures. [NIH] Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus. [EU]

Glomeruli: Plural of glomerulus. [NIH] Glomerulonephritis: Glomerular disease characterized by an inflammatory reaction, with leukocyte infiltration and cellular proliferation of the glomeruli, or that appears to be the result of immune glomerular injury. [NIH] Glucocorticoids: A group of corticosteroids that affect carbohydrate metabolism (gluconeogenesis, liver glycogen deposition, elevation of blood sugar), inhibit corticotropin secretion, and possess pronounced anti-inflammatory activity. They also play a role in fat and protein metabolism, maintenance of arterial blood pressure, alteration of the connective tissue response to injury, reduction in the number of circulating lymphocytes, and functioning of the central nervous system. [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] Glucuronic Acid: Derivatives of uronic acid found throughout the plant and animal kingdoms. They detoxify drugs and toxins by conjugating with them to form glucuronides in the liver which are more water-soluble metabolites that can be easily eliminated from the body. [NIH] Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid

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(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] Glycerol: A trihydroxy sugar alcohol that is an intermediate in carbohydrate and lipid metabolism. It is used as a solvent, emollient, pharmaceutical agent, and sweetening agent. [NIH]

Glycerophospholipids: Derivatives of phosphatidic acid in which the hydrophobic regions are composed of two fatty acids and a polar alcohol is joined to the C-3 position of glycerol through a phosphodiester bond. They are named according to their polar head groups, such as phosphatidylcholine and phosphatidylethanolamine. [NIH] Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Glycosidic: Formed by elimination of water between the anomeric hydroxyl of one sugar and a hydroxyl of another sugar molecule. [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] Gonads: The gamete-producing glands, ovary or testis. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Gp120: 120-kD HIV envelope glycoprotein which is involved in the binding of the virus to its membrane receptor, the CD4 molecule, found on the surface of certain cells in the body. [NIH]

Grade: The grade of a tumor depends on how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread. Grading systems are different for each type of cancer. [NIH] Grading: A system for classifying cancer cells in terms of how abnormal they appear when examined under a microscope. The objective of a grading system is to provide information about the probable growth rate of the tumor and its tendency to spread. The systems used to grade tumors vary with each type of cancer. Grading plays a role in treatment decisions. [NIH]

Grafting: The operation of transfer of tissue from one site to another. [NIH] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [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] 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

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therapy. [NIH] Habitat: An area considered in terms of its environment, particularly as this determines the type and quality of the vegetation the area can carry. [NIH] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH] Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Headache Disorders: Common conditions characterized by persistent or recurrent headaches. Headache syndrome classification systems may be based on etiology (e.g., vascular headache, post-traumatic headaches, etc.), temporal pattern (e.g., cluster headache, paroxysmal hemicrania, etc.), and precipitating factors (e.g., cough headache). [NIH] Health Status: The level of health of the individual, group, or population as subjectively assessed by the individual or by more objective measures. [NIH] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] 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] Hematuria: Presence of blood in the urine. [NIH] Hemodialysis: The use of a machine to clean wastes from the blood after the kidneys have failed. The blood travels through tubes to a dialyzer, which removes wastes and extra fluid. The cleaned blood then flows through another set of tubes back into the body. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] Hemoglobinopathies: A group of inherited disorders characterized by structural alterations within the hemoglobin molecule. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemostasis: The process which spontaneously arrests the flow of blood from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation. [NIH]

Heparan Sulfate Proteoglycan: A substance released by astrocytes, which is critical in stopping nervous fibers in their tracks. [NIH] Heparin: Heparinic acid. A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver,

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lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts. [NIH] Heparin-binding: Protein that stimulates the proliferation of endothelial cells. [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] Heterodimers: Zippered pair of nonidentical proteins. [NIH] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]

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]

Histamine: 1H-Imidazole-4-ethanamine. A depressor amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. [NIH] Histidine: An essential amino acid important in a number of metabolic processes. It is required for the production of histamine. [NIH] Histology: The study of tissues and cells under a microscope. [NIH] Histones: Small chromosomal proteins (approx 12-20 kD) possessing an open, unfolded structure and attached to the DNA in cell nuclei by ionic linkages. Classification into the various types (designated histone I, histone II, etc.) is based on the relative amounts of arginine and lysine in each. [NIH] Holmium: An element of the rare earth family of metals. It has the atomic symbol Ho, atomic number 67, and atomic weight 164.93. [NIH] Homeobox: Distinctive sequence of DNA bases. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] 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 therapy: Treatment of cancer by removing, blocking, or adding hormones. Also called endocrine therapy. [NIH] Human papillomavirus: HPV. A virus that causes abnormal tissue growth (warts) and is often associated with some types of cancer. [NIH] Humoral: Of, relating to, proceeding from, or involving a bodily humour - now often used of endocrine factors as opposed to neural or somatic. [EU] Humour: 1. A normal functioning fluid or semifluid of the body (as the blood, lymph or

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bile) especially of vertebrates. 2. A secretion that is itself an excitant of activity (as certain hormones). [EU] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hybridization: The genetic process of crossbreeding to produce a hybrid. Hybrid nucleic acids can be formed by nucleic acid hybridization of DNA and RNA molecules. Protein hybridization allows for hybrid proteins to be formed from polypeptide chains. [NIH] Hybridomas: Cells artificially created by fusion of activated lymphocytes with neoplastic cells. The resulting hybrid cells are cloned and produce pure or "monoclonal" antibodies or T-cell products, identical to those produced by the immunologically competent parent, and continually grow and divide as the neoplastic parent. [NIH] 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] Hydronephrosis: Abnormal enlargement of a kidney, which may be caused by blockage of the ureter (such as by a kidney stone) or chronic kidney disease that prevents urine from draining into the bladder. [NIH] 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] Hydroxysteroid Dehydrogenases: Enzymes of the oxidoreductase class that catalyze the dehydrogenation of hydroxysteroids. (From Enzyme Nomenclature, 1992) EC 1.1.-. [NIH] Hydroxysteroids: Steroids in which one or more hydroxy groups have been substituted for hydrogen atoms either within the ring skeleton or on any of the side chains. [NIH] 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] Hyperlipidaemia: A general term for elevated concentrations of any or all of the lipids in the plasma, including hyperlipoproteinaemia, hypercholesterolaemia, etc. [EU] Hyperplasia: An increase in the number of cells in a tissue or organ, not due to tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. [NIH] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hyperstimulation: Excessive stimulation. [EU] 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] Hypertrichosis: Localized or generalized excess hair. The concept does not include hirsutism, which is excess hair in females and children with an adult male pattern of distribution. [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] Hypogonadism: Condition resulting from or characterized by abnormally decreased functional activity of the gonads, with retardation of growth and sexual development. [NIH] Hypospadias: A developmental anomaly in the male in which the urethra opens on the underside of the penis or on the perineum. [NIH] Hypotension: Abnormally low blood pressure. [NIH] Hypotensive: Characterized by or causing diminished tension or pressure, as abnormally low blood pressure. [EU] Hypothalamus: Ventral part of the diencephalon extending from the region of the optic chiasm to the caudal border of the mammillary bodies and forming the inferior and lateral walls of the third ventricle. [NIH] Hypothermia: Lower than normal body temperature, especially in warm-blooded animals; in man usually accidental or unintentional. [NIH] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU] Hypoxic: Having too little oxygen. [NIH] Imaging procedures: Methods of producing pictures of areas inside the body. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]

Immune Sera: Serum that contains antibodies. It is obtained from an animal that has been immunized either by antigen injection or infection with microorganisms containing the antigen. [NIH] Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunity: Nonsusceptibility to the invasive or pathogenic microorganisms or to the toxic effect of antigenic substances. [NIH]

effects

of

foreign

Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunoassay: Immunochemical assay or detection of a substance by serologic or immunologic methods. Usually the substance being studied serves as antigen both in antibody production and in measurement of antibody by the test substance. [NIH] Immunoblotting: Immunologic methods for isolating and quantitatively measuring immunoreactive substances. When used with immune reagents such as monoclonal antibodies, the process is known generically as western blot analysis (blotting, western). [NIH]

Immunogenic: Producing immunity; evoking an immune response. [EU] Immunohistochemistry: Histochemical localization of immunoreactive substances using

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labeled antibodies as reagents. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunology: The study of the body's immune system. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Implant radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called [NIH] Implantation: The insertion or grafting into the body of biological, living, inert, or radioactive material. [EU] Impotence: The inability to perform sexual intercourse. [NIH] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes. [NIH] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incidental: 1. Small and relatively unimportant, minor; 2. Accompanying, but not a major part of something; 3. (To something) Liable to occur because of something or in connection with something (said of risks, responsibilities, .) [EU] 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] Indolent: A type of cancer that grows slowly. [NIH] Indoramin: A hypotensive agent with some anti-arrhythmic effects. [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] Induration: 1. The quality of being hard; the process of hardening. 2. An abnormally hard spot or place. [EU] Infant, Newborn: An infant during the first month after birth. [NIH] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]

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Infertility: The diminished or absent ability to conceive or produce an offspring while sterility is the complete inability to conceive or produce an offspring. [NIH] Infiltration: The diffusion or accumulation in a tissue or cells of substances not normal to it or in amounts of the normal. Also, the material so accumulated. [EU] Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Informed Consent: Voluntary authorization, given to the physician by the patient, with full comprehension of the risks involved, for diagnostic or investigative procedures and medical and surgical treatment. [NIH] Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Innervation: 1. The distribution or supply of nerves to a part. 2. The supply of nervous energy or of nerve stimulus sent to a part. [EU] Inorganic: Pertaining to substances not of organic origin. [EU] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune, genetic, and environmental factors are involved in the development of type I diabetes. [NIH] Insulin-like: Muscular growth factor. [NIH] Insulin-Like Growth Factor Binding Protein 3: One of the six homologous soluble proteins that bind insulin-like growth factors (somatomedins) and modulate their mitogenic and metabolic actions at the cellular level. [NIH] Integrins: A family of transmembrane glycoproteins consisting of noncovalent heterodimers. They interact with a wide variety of ligands including extracellular matrix glycoproteins, complement, and other cells, while their intracellular domains interact with the cytoskeleton. The integrins consist of at least three identified families: the cytoadhesin receptors, the leukocyte adhesion receptors, and the very-late-antigen receptors. Each family contains a common beta-subunit combined with one or more distinct alpha-subunits. These receptors participate in cell-matrix and cell-cell adhesion in many physiologically important processes, including embryological development, hemostasis, thrombosis, wound healing, immune and nonimmune defense mechanisms, and oncogenic transformation. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Internal Medicine: A medical specialty concerned with the diagnosis and treatment of diseases of the internal organ systems of adults. [NIH] Internal radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called brachytherapy, implant radiation, or interstitial radiation therapy. [NIH] Interneurons: Most generally any neurons which are not motor or sensory. Interneurons

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may also refer to neurons whose axons remain within a particular brain region as contrasted with projection neurons which have axons projecting to other brain regions. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intestinal: Having to do with the intestines. [NIH] Intestines: The section of the alimentary canal from the stomach to the anus. It includes the large intestine and small intestine. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intracellular Membranes: Membranes of subcellular structures. [NIH] Intraepithelial: Within the layer of cells that form the surface or lining of an organ. [NIH] Intraocular: Within the eye. [EU] Intraocular pressure: Pressure of the fluid inside the eye; normal IOP varies among individuals. [NIH] Intrathecal: Describes the fluid-filled space between the thin layers of tissue that cover the brain and spinal cord. Drugs can be injected into the fluid or a sample of the fluid can be removed for testing. [NIH] Intravenous: IV. Into a vein. [NIH] Intravenous pyelogram: IVP. A series of x-rays of the kidneys, ureters, and bladder. The xrays are taken after a dye is injected into a blood vessel. The dye is concentrated in the urine, which outlines the kidneys, ureters, and bladder on the x-rays. [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] Involution: 1. A rolling or turning inward. 2. One of the movements involved in the gastrulation of many animals. 3. A retrograde change of the entire body or in a particular organ, as the retrograde changes in the female genital organs that result in normal size after delivery. 4. The progressive degeneration occurring naturally with advancing age, resulting in shrivelling of organs or tissues. [EU] Ionization: 1. Any process by which a neutral atom gains or loses electrons, thus acquiring a net charge, as the dissociation of a substance in solution into ions or ion production by the passage of radioactive particles. 2. Iontophoresis. [EU] 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] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Isoflavones: 3-Phenylchromones. Isomeric form of flavones in which the benzene group is attached to the 3 position of the benzopyran ring instead of the 2 position. [NIH] Isoleucine: An essential branched-chain amino acid found in many proteins. It is an isomer of LEUCINE. It is important in hemoglobin synthesis and regulation of blood sugar and

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energy levels. [NIH] Isoproterenol: Isopropyl analog of epinephrine; beta-sympathomimetic that acts on the heart, bronchi, skeletal muscle, alimentary tract, etc. It is used mainly as bronchodilator and heart stimulant. [NIH] Kallikreins: Proteolytic enzymes from the serine endopeptidase family found in normal blood and urine. Specifically, Kallikreins are potent vasodilators and hypotensives and increases vascular permeability and affects smooth muscle. They act as infertility agents in men. Three forms are recognized, plasma kallikrein (EC 3.4.21.34), tissue kallikrein (EC 3.4.21.35), and prostate-specific antigen (EC 3.4.21.77). [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] Keratinocyte growth factor: A substance that stimulates the growth of epithelial cells that line the surface of the mouth and intestinal tract. [NIH] Kidney Disease: Any one of several chronic conditions that are caused by damage to the cells of the kidney. People who have had diabetes for a long time may have kidney damage. Also called nephropathy. [NIH] Kidney Failure: The inability of a kidney to excrete metabolites at normal plasma levels under conditions of normal loading, or the inability to retain electrolytes under conditions of normal intake. In the acute form (kidney failure, acute), it is marked by uremia and usually by oliguria or anuria, with hyperkalemia and pulmonary edema. The chronic form (kidney failure, chronic) is irreversible and requires hemodialysis. [NIH] Kidney Failure, Acute: A clinical syndrome characterized by a sudden decrease in glomerular filtration rate, often to values of less than 1 to 2 ml per minute. It is usually associated with oliguria (urine volumes of less than 400 ml per day) and is always associated with biochemical consequences of the reduction in glomerular filtration rate such as a rise in blood urea nitrogen (BUN) and serum creatinine concentrations. [NIH] Kidney Failure, Chronic: An irreversible and usually progressive reduction in renal function in which both kidneys have been damaged by a variety of diseases to the extent that they are unable to adequately remove the metabolic products from the blood and regulate the body's electrolyte composition and acid-base balance. Chronic kidney failure requires hemodialysis or surgery, usually kidney transplantation. [NIH] Kidney stone: A stone that develops from crystals that form in urine and build up on the inner surfaces of the kidney, in the renal pelvis, or in the ureters. [NIH] Kidney Transplantation: The transference of a kidney from one human or animal to another. [NIH] Kilobase: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [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] Lactosylceramides: Glycosphingolipids which contain as their polar head group a lactose moiety bound in glycosidic linkage to the hydroxyl group of ceramide. Their accumulation in tissue, due to a defect in lactosylceramide beta-galactosidase, is the cause of lactosylceramidosis. [NIH] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large

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intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Laser Coagulation: The coagulation of tissues using lasers. These lasers produce light in the visible green wavelength that is selectively absorbed by hemoglobin, and thus it is possible to seal bleeding blood vessels. [NIH] Laser Surgery: The use of a laser either to vaporize surface lesions or to make bloodless cuts in tissue. It does not include the coagulation of tissue by laser. [NIH] Laser therapy: The use of an intensely powerful beam of light to kill cancer cells. [NIH] Lectin: A complex molecule that has both protein and sugars. Lectins are able to bind to the outside of a cell and cause biochemical changes in it. Lectins are made by both animals and plants. [NIH] Lens: The transparent, double convex (outward curve on both sides) structure suspended between the aqueous and vitreous; helps to focus light on the retina. [NIH] 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] Leucocyte: All the white cells of the blood and their precursors (myeloid cell series, lymphoid cell series) but commonly used to indicate granulocytes exclusive of lymphocytes. [NIH]

Leukemia: Cancer of blood-forming tissue. [NIH] 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] Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] Ligands: A RNA simulation method developed by the MIT. [NIH] Ligation: Application of a ligature to tie a vessel or strangulate a part. [NIH] Linkage: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Lipid: Fat. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] Lithotripsy: The destruction of a calculus of the kidney, ureter, bladder, or gallbladder by physical forces, including crushing with a lithotriptor through a catheter. Focused percutaneous ultrasound and focused hydraulic shock waves may be used without surgery. Lithotripsy does not include the dissolving of stones by acids or litholysis. Lithotripsy by laser is laser lithotripsy. [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 Cirrhosis: Liver disease in which the normal microcirculation, the gross vascular anatomy, and the hepatic architecture have been variably destroyed and altered with fibrous septa surrounding regenerated or regenerating parenchymal nodules. [NIH] 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] 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] Lutein Cells: The cells of the corpus luteum which are derived from the granulosa cells and the theca cells of the Graafian follicle. [NIH] Luteinizing hormone-releasing hormone agonist: LH-RH agonist. A drug that inhibits the secretion of sex hormones. In men, LH-RH agonist causes testosterone levels to fall. In women, LH-RH agonist causes the levels of estrogen and other sex hormones to fall. [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]

Lymphadenectomy: A surgical procedure in which the lymph nodes are removed and examined to see whether they contain cancer. Also called lymph node dissection. [NIH] Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] Lymphocytes: White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each); those with characteristics of neither major class are called null cells. [NIH] 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] Lysine: An essential amino acid. It is often added to animal feed. [NIH] Maintenance therapy: Treatment that is given to help a primary (original) treatment keep working. Maintenance therapy is often given to help keep cancer in remission. [NIH] Malignancy: A cancerous tumor that can invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant tumor: A tumor capable of metastasizing. [NIH]

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Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]

Mammary: Pertaining to the mamma, or breast. [EU] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] 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] 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 castration: Refers to the use of drugs to suppress the function of the ovaries or testicles. [NIH] Medical Records: Recording of pertinent information concerning patient's illness or illnesses. [NIH] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Meiosis: A special method of cell division, occurring in maturation of the germ cells, by means of which each daughter nucleus receives half the number of chromosomes characteristic of the somatic cells of the species. [NIH] Melanin: The substance that gives the skin its color. [NIH] Melanocytes: Epidermal dendritic pigment cells which control long-term morphological color changes by alteration in their number or in the amount of pigment they produce and store in the pigment containing organelles called melanosomes. Melanophores are larger cells which do not exist in mammals. [NIH] Melanoma: A form of skin cancer that arises in melanocytes, the cells that produce pigment. Melanoma usually begins in a mole. [NIH] Melanosis: Disorders of increased melanin pigmentation that develop without preceding inflammatory disease. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Lipids: Lipids, predominantly phospholipids, cholesterol and small amounts of glycolipids found in membranes including cellular and intracellular membranes. These lipids may be arranged in bilayers in the membranes with integral proteins between the layers and peripheral proteins attached to the outside. Membrane lipids are required for active transport, several enzymatic activities and membrane formation. [NIH] Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Menopause: Permanent cessation of menstruation. [NIH] Menstrual Cycle: The period of the regularly recurring physiologic changes in the endometrium occurring during the reproductive period in human females and some

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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: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH] Mercury: A silver metallic element that exists as a liquid at room temperature. It has the atomic symbol Hg (from hydrargyrum, liquid silver), atomic number 80, and atomic weight 200.59. Mercury is used in many industrial applications and its salts have been employed therapeutically as purgatives, antisyphilitics, disinfectants, and astringents. It can be absorbed through the skin and mucous membranes which leads to mercury poisoning. Because of its toxicity, the clinical use of mercury and mercurials is diminishing. [NIH] Mesenchymal: Refers to cells that develop into connective tissue, blood vessels, and lymphatic tissue. [NIH] Meta-Analysis: A quantitative method of combining the results of independent studies (usually drawn from the published literature) and synthesizing summaries and conclusions which may be used to evaluate therapeutic effectiveness, plan new studies, etc., with application chiefly in the areas of research and medicine. [NIH] Metabolic disorder: A condition in which normal metabolic processes are disrupted, usually because of a missing enzyme. [NIH] Metaphase: The second phase of cell division, in which the chromosomes line up across the equatorial plane of the spindle prior to separation. [NIH] Metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors" and contain cells that are like those in the original (primary) tumor. The plural is metastases. [NIH] Metastatic: Having to do with metastasis, which is the spread of cancer from one part of the body to another. [NIH] Microcirculation: The vascular network lying between the arterioles and venules; includes capillaries, metarterioles and arteriovenous anastomoses. Also, the flow of blood through this network. [NIH] 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] Microwaves: That portion of the electromagnetic spectrum lying between UHF (ultrahigh frequency) radio waves and heat (infrared) waves. Microwaves are used to generate heat, especially in some types of diathermy. They may cause heat damage to tissues. [NIH] Micturition: The passage of urine; urination. [EU] Milk Thistle: The plant Silybum marianum in the family Asteraceae containing the bioflavonoid complex silymarin. For centuries this has been used traditionally to treat liver disease. [NIH] Mineralocorticoids: A group of corticosteroids primarily associated with the regulation of water and electrolyte balance. This is accomplished through the effect on ion transport in renal tubules, resulting in retention of sodium and loss of potassium. Mineralocorticoid secretion is itself regulated by plasma volume, serum potassium, and angiotensin II. [NIH]

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Mitochondrial Swelling: Increase in volume of mitochondria due to an influx of fluid; it occurs in hypotonic solutions due to osmotic pressure and in isotonic solutions as a result of altered permeability of the membranes of respiring mitochondria. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] 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] Molecular mass: The sum of the atomic masses of all atoms in a molecule, based on a scale in which the atomic masses of hydrogen, carbon, nitrogen, and oxygen are 1, 12, 14, and 16, respectively. For example, the molecular mass of water, which has two atoms of hydrogen and one atom of oxygen, is 18 (i.e., 2 + 16). [NIH] Molecular Probes: A group of atoms or molecules attached to other molecules or cellular structures and used in studying the properties of these molecules and structures. Radioactive DNA or RNA sequences are used in molecular genetics to detect the presence of a complementary sequence by molecular hybridization. [NIH] Molecular Structure: The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds. [NIH] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] 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] Mononuclear: A cell with one nucleus. [NIH] Monophosphate: So called second messenger for neurotransmitters and hormones. [NIH] Monotherapy: A therapy which uses only one drug. [EU] Morphogenesis: The development of the form of an organ, part of the body, or organism. [NIH]

Morphological: Relating to the configuration or the structure of live organs. [NIH] Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Mucosa: A mucous membrane, or tunica mucosa. [EU]

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Multicenter Studies: Controlled studies which are planned and carried out by several cooperating institutions to assess certain variables and outcomes in specific patient populations, for example, a multicenter study of congenital anomalies in children. [NIH] Multicenter study: A clinical trial that is carried out at more than one medical institution. [NIH]

Muscarine: A toxic alkaloid found in Amanita muscaria (fly fungus) and other fungi of the Inocybe species. It is the first parasympathomimetic substance ever studied and causes profound parasympathetic activation that may end in convulsions and death. The specific antidote is atropine. [NIH] Muscle Contraction: A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments. [NIH] Muscle Fibers: Large single cells, either cylindrical or prismatic in shape, that form the basic unit of muscle tissue. They consist of a soft contractile substance enclosed in a tubular sheath. [NIH] Muscular Atrophy: Derangement in size and number of muscle fibers occurring with aging, reduction in blood supply, or following immobilization, prolonged weightlessness, malnutrition, and particularly in denervation. [NIH] Mutagenesis: Process of generating genetic mutations. It may occur spontaneously or be induced by mutagens. [NIH] Mutagenic: Inducing genetic mutation. [EU] Mutagens: Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. [NIH] Myocardial infarction: Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Naphazoline: An adrenergic vasoconstrictor agent used as a decongestant. [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] Needle biopsy: The removal of tissue or fluid with a needle for examination under a microscope. Also called fine-needle aspiration. [NIH] Needs Assessment: Systematic identification of a population's needs or the assessment of individuals to determine the proper level of services needed. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU]

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Neoplasia: Abnormal and uncontrolled cell growth. [NIH] Neoplasm: A new growth of benign or malignant tissue. [NIH] Neoplastic Processes: The pathological mechanisms and forms taken by tissue during degeneration into a neoplasm and its subsequent activity. [NIH] Nephrolithiasis: Kidney stones. [NIH] Nephrology: A subspecialty of internal medicine concerned with the anatomy, physiology, and pathology of the kidney. [NIH] Nephropathy: Disease of the kidneys. [EU] Nephrosis: Descriptive histopathologic term for renal disease without an inflammatory component. [NIH] Nephrotic: Pertaining to, resembling, or caused by nephrosis. [EU] Nephrotic Syndrome: Clinical association of heavy proteinuria, hypoalbuminemia, and generalized edema. [NIH] Nerve Endings: Specialized terminations of peripheral neurons. Nerve endings include neuroeffector junction(s) by which neurons activate target organs and sensory receptors which transduce information from the various sensory modalities and send it centrally in the nervous system. Presynaptic nerve endings are presynaptic terminals. [NIH] Nerve Growth Factor: Nerve growth factor is the first of a series of neurotrophic factors that were found to influence the growth and differentiation of sympathetic and sensory neurons. It is comprised of alpha, beta, and gamma subunits. The beta subunit is responsible for its growth stimulating activity. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Networks: Pertaining to a nerve or to the nerves, a meshlike structure of interlocking fibers or strands. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neuroeffector Junction: The synapse between a neuron (presynaptic) and an effector cell other than another neuron (postsynaptic). Neuroeffector junctions include synapses onto muscles and onto secretory cells. [NIH] Neuroendocrine: Having to do with the interactions between the nervous system and the endocrine system. Describes certain cells that release hormones into the blood in response to stimulation of the nervous system. [NIH] Neurogenic: Loss of bladder control caused by damage to the nerves controlling the bladder. [NIH] Neurologic: Having to do with nerves or the nervous system. [NIH] Neuromuscular: Pertaining to muscles and nerves. [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] Neurotransmitter: Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel across the synaptic cleft to either excite or inhibit the target cell. Among the many substances that have the properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic acid, substance P, enkephalins,

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endorphins, and serotonin. [EU] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] Niche: The ultimate unit of the habitat, i. e. the specific spot occupied by an individual organism; by extension, the more or less specialized relationships existing between an organism, individual or synusia(e), and its environment. [NIH] Nickel: A trace element with the atomic symbol Ni, atomic number 28, and atomic weight 58.69. It is a cofactor of the enzyme urease. [NIH] Nitrates: Inorganic or organic salts and esters of nitric acid. These compounds contain the NO3- radical. [NIH] Nitric acid: A toxic, corrosive, colorless liquid used to make fertilizers, dyes, explosives, and other chemicals. [NIH] 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] Nonmalignant: Not cancerous. [NIH] Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] Normotensive: 1. Characterized by normal tone, tension, or pressure, as by normal blood pressure. 2. A person with normal blood pressure. [EU] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleic Acid Hybridization: The process whereby two single-stranded polynucleotides form a double-stranded molecule, with hydrogen bonding between the complementary bases in the two strains. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Observational study: An epidemiologic study that does not involve any intervention, experimental or otherwise. Such a study may be one in which nature is allowed to take its course, with changes in one characteristic being studied in relation to changes in other 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]

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Odds Ratio: The ratio of two odds. The exposure-odds ratio for case control data is the ratio of the odds in favor of exposure among cases to the odds in favor of exposure among noncases. The disease-odds ratio for a cohort or cross section is the ratio of the odds in favor of disease among the exposed to the odds in favor of disease among the unexposed. The prevalence-odds ratio refers to an odds ratio derived cross-sectionally from studies of prevalent cases. [NIH] Office Visits: Visits made by patients to health service providers' offices for diagnosis, treatment, and follow-up. [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] Oncogenes: Genes which can potentially induce neoplastic transformation. They include genes for growth factors, growth factor receptors, protein kinases, signal transducers, nuclear phosphoproteins, and transcription factors. When these genes are constitutively expressed after structural and/or regulatory changes, uncontrolled cell proliferation may result. Viral oncogenes have prefix "v-" before the gene symbol; cellular oncogenes (protooncogenes) have the prefix "c-" before the gene symbol. [NIH] Oncogenic: Chemical, viral, radioactive or other agent that causes cancer; carcinogenic. [NIH] Oncology: The study of cancer. [NIH] Oophorectomy: Surgery to remove one or both ovaries. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Ophthalmic: Pertaining to the eye. [EU] Orchiectomy: The surgical removal of one or both testicles. [NIH] Organ Culture: The growth in aseptic culture of plant organs such as roots or shoots, beginning with organ primordia or segments and maintaining the characteristics of the organ. [NIH] Organogenesis: Clonal propagation which involves culturing explants from roots, leaves, or stems to form undifferentiated callus tissue; after the cells form shoots, they are separated and rooted. Alternatively, if the callus is put in liquid culture, somatic embryos form. [NIH] Orgasm: The crisis of sexual excitement in either humans or animals. [NIH] Orthostatic: Pertaining to or caused by standing erect. [EU] Osmotic: Pertaining to or of the nature of osmosis (= the passage of pure solvent from a solution of lesser to one of greater solute concentration when the two solutions are separated by a membrane which selectively prevents the passage of solute molecules, but is permeable to the solvent). [EU] Osteoporosis: Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal osteoporosis and age-related (or senile) osteoporosis. [NIH] Outpatient: A patient who is not an inmate of a hospital but receives diagnosis or treatment in a clinic or dispensary connected with the hospital. [NIH] Ovarian Follicle: Spheroidal cell aggregation in the ovary containing an ovum. It consists of an external fibro-vascular coat, an internal coat of nucleated cells, and a transparent, albuminous fluid in which the ovum is suspended. [NIH]

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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] Overactive bladder: A condition in which the patient experiences two or all three of the following conditions: [NIH] Ovulation: The discharge of a secondary oocyte from a ruptured graafian follicle. [NIH] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Oxalate: A chemical that combines with calcium in urine to form the most common type of kidney stone (calcium oxalate stone). [NIH] Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]

Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). [NIH] Oxides: Binary compounds of oxygen containing the anion O(2-). The anion combines with metals to form alkaline oxides and non-metals to form acidic oxides. [NIH] Painful bladder syndrome: Another name for interstitial cystitis. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Pancreatic Juice: The fluid containing digestive enzymes secreted by the pancreas in response to food in the duodenum. [NIH] Papillomavirus: A genus of Papovaviridae causing proliferation of the epithelium, which may lead to malignancy. A wide range of animals are infected including humans, chimpanzees, cattle, rabbits, dogs, and horses. [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] Paralysis: Loss of ability to move all or part of the body. [NIH] Parasympathomimetic: 1. Producing effects resembling those of stimulation of the parasympathetic nerve supply to a part. 2. An agent that produces effects similar to those produced by stimulation of the parasympathetic nerves. Called also cholinergic. [EU] Paresthesia: Subjective cutaneous sensations (e.g., cold, warmth, tingling, pressure, etc.) that are experienced spontaneously in the absence of stimulation. [NIH] Partial remission: The shrinking, but not complete disappearance, of a tumor in response to therapy. Also called partial response. [NIH]

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Particle: A tiny mass of material. [EU] Parturition: The act or process of given birth to a child. [EU] Patch: A piece of material used to cover or protect a wound, an injured part, etc.: a patch over the eye. [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]

Patient Selection: Criteria and standards used for the determination of the appropriateness of the inclusion of patients with specific conditions in proposed treatment plans and the criteria used for the inclusion of subjects in various clinical trials and other research protocols. [NIH] Pelvic: Pertaining to the pelvis. [EU] Pelvis: The lower part of the abdomen, located between the hip bones. [NIH] Penicillin: An antibiotic drug used to treat infection. [NIH] Penile Prosthesis: Rigid, semi-rigid, or inflatable cylindric hydraulic devices, with either combined or separate reservoir and pumping systems, implanted for the surgical treatment of organic impotence. [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] 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] Perforation: 1. The act of boring or piercing through a part. 2. A hole made through a part or substance. [EU] Perfusion: Bathing an organ or tissue with a fluid. In regional perfusion, a specific area of the body (usually an arm or a leg) receives high doses of anticancer drugs through a blood vessel. Such a procedure is performed to treat cancer that has not spread. [NIH] 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]

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Perineal: Pertaining to the perineum. [EU] Perineum: The area between the anus and the sex organs. [NIH] Perioperative: Around the time of surgery; usually lasts from the time of going into the hospital or doctor's office for surgery until the time the patient goes home. [NIH] Perioperative Care: Interventions to provide care prior to, during, and immediately after surgery. [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] Petroleum: Naturally occurring complex liquid hydrocarbons which, after distillation, yield combustible fuels, petrochemicals, and lubricants. [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] Pharmacotherapy: A regimen of using appetite suppressant medications to manage obesity by decreasing appetite or increasing the feeling of satiety. These medications decrease appetite by increasing serotonin or catecholamine—two brain chemicals that affect mood and appetite. [NIH] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phenoxybenzamine: An alpha-adrenergic anatagonist with long duration of action. It has been used to treat hypertension and as a peripheral vasodilator. [NIH] Phenyl: Ingredient used in cold and flu remedies. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Phosphorylated: Attached to a phosphate group. [NIH] Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. [NIH]

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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] Pigment: A substance that gives color to tissue. Pigments are responsible for the color of skin, eyes, and hair. [NIH] Pilot study: The initial study examining a new method or treatment. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [NIH] Placenta: A highly vascular fetal organ through which the fetus absorbs oxygen and other nutrients and excretes carbon dioxide and other wastes. It begins to form about the eighth day of gestation when the blastocyst adheres to the decidua. [NIH] Plant Oils: Oils derived from plants or plant products. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasma Kallikrein: A peptidohydrolytic enzyme that is formed from prekallikrein by factor XIIA. It activates factor XII, factor VII, and plasminogen. It is selective for both arginine and to a lesser extent lysinebonds. EC 3.4.21.34. [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] Plasmids: Any extrachromosomal hereditary determinant. Plasmids are self-replicating circular molecules of DNA that are found in a variety of bacterial, archaeal, fungal, algal, and plant species. [NIH] Plasticity: In an individual or a population, the capacity for adaptation: a) through gene changes (genetic plasticity) or b) through internal physiological modifications in response to changes of environment (physiological plasticity). [NIH] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Pneumonia: Inflammation of the lungs. [NIH]

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Pollen: The male fertilizing element of flowering plants analogous to sperm in animals. It is released from the anthers as yellow dust, to be carried by insect or other vectors, including wind, to the ovary (stigma) of other flowers to produce the embryo enclosed by the seed. The pollens of many plants are allergenic. [NIH] Polycystic: An inherited disorder characterized by many grape-like clusters of fluid-filled cysts that make both kidneys larger over time. These cysts take over and destroy working kidney tissue. PKD may cause chronic renal failure and end-stage renal disease. [NIH] Polycystic Ovary Syndrome: Clinical symptom complex characterized by oligomenorrhea or amenorrhea, anovulation, and regularly associated with bilateral polycystic ovaries. [NIH] 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] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Polyvinyl Alcohol: A polymer prepared from polyvinyl acetates by replacement of the acetate groups with hydroxyl groups. It is used as a pharmaceutic aid and ophthalmic lubricant as well as in the manufacture of surface coatings artificial sponges, cosmetics, and other products. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postmenopausal: Refers to the time after menopause. Menopause is the time in a woman's life when menstrual periods stop permanently; also called "change of life." [NIH] Postnatal: Occurring after birth, with reference to the newborn. [EU] Postoperative: After surgery. [NIH] Postoperative Complications: Pathologic processes that affect patients after a surgical procedure. They may or may not be related to the disease for which the surgery was done, and they may or may not be direct results of the surgery. [NIH] Postoperative Period: The period following a surgical operation. [NIH] 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] Postural: Pertaining to posture or position. [EU] Potentiates: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] Practicability: A non-standard characteristic of an analytical procedure. It is dependent on the scope of the method and is determined by requirements such as sample throughout and costs. [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,

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therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Prazosin: A selective adrenergic alpha-1 antagonist used in the treatment of heart failure, hypertension, pheochromocytoma, Raynaud's syndrome, prostatic hypertrophy, and urinary retention. [NIH] 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] 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] Premalignant: A term used to describe a condition that may (or is likely to) become cancer. Also called precancerous. [NIH] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Preoperative: Preceding an operation. [EU] Prepuce: A covering fold of skin; often used alone to designate the preputium penis. [EU] Presynaptic: Situated proximal to a synapse, or occurring before the synapse is crossed. [EU] Presynaptic Terminals: The distal terminations of axons which are specialized for the release of neurotransmitters. Also included are varicosities along the course of axons which have similar specializations and also release transmitters. Presynaptic terminals in both the central and peripheral nervous systems are included. [NIH] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Priapism: Persistent abnormal erection of the penis, usually without sexual desire, and accompanied by pain and tenderness. It is seen in diseases and injuries of the spinal cord, and may be caused by vesical calculus and certain injuries to the penis. [EU] 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] Primum: The first atrial septum to appear in the embryonic heart. [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] Problem Solving: A learning situation involving more than one alternative from which a selection is made in order to attain a specific goal. [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

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the uterus for the reception and development of the fertilized ovum. It acts as an antiovulatory agent when administered on days 5-25 of the menstrual cycle. [NIH] Prognostic factor: A situation or condition, or a characteristic of a patient, that can be used to estimate the chance of recovery from a disease, or the chance of the disease recurring (coming back). [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Progressive disease: Cancer that is increasing in scope or severity. [NIH] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH] 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] Prone: Having the front portion of the body downwards. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Prospective Studies: Observation of a population for a sufficient number of persons over a sufficient number of years to generate incidence or mortality rates subsequent to the selection of the study group. [NIH] Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] 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] Prostate-Specific Antigen: Kallikrein-like serine proteinase produced by epithelial cells of both benign and malignant prostate tissue. It is an important marker for the diagnosis of prostate cancer. EC 3.4.21.77. [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

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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] Prostatism: A symptom complex resulting from compression or obstruction of the urethra, due most commonly to hyperplasia of the prostate; symptoms include diminution in the calibre and force of the urinary stream, hesitancy in initiating voiding, inability to terminate micturition abruptly (with postvoiding dribbling), a sensation of incomplete bladder emptying, and, occasionally, urinary retention. [EU] Prostatitis: Inflammation of the prostate. [EU] Prosthesis: An artificial replacement of a part of the body. [NIH] Prosthesis Implantation: Surgical insertion of a prosthesis. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protease Inhibitors: Compounds which inhibit or antagonize biosynthesis or actions of proteases (endopeptidases). [NIH] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. Quaternary protein structure describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). [NIH] Protein Kinases: A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein. EC 2.7.1.37. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Proteinuria: The presence of protein in the urine, indicating that the kidneys are not working properly. [NIH] Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Psychoactive: Those drugs which alter sensation, mood, consciousness or other psychological or behavioral functions. [NIH] Psychogenic: Produced or caused by psychic or mental factors rather than organic factors. [EU]

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Puberty: The period during which the secondary sex characteristics begin to develop and the capability of sexual reproduction is attained. [EU] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]

Pulmonary: Relating to the lungs. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] Pulmonary Edema: An accumulation of an excessive amount of watery fluid in the lungs, may be caused by acute exposure to dangerous concentrations of irritant gasses. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]

Purines: A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include adenine and guanine, constituents of nucleic acids, as well as many alkaloids such as caffeine and theophylline. Uric acid is the metabolic end product of purine metabolism. [NIH] Pustular: Pertaining to or of the nature of a pustule; consisting of pustules (= a visible collection of pus within or beneath the epidermis). [EU] Pyelonephritis: Inflammation of the kidney and its pelvis, beginning in the interstitium and rapidly extending to involve the tubules, glomeruli, and blood vessels; due to bacterial infection. [EU] Pyrimidines: A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (cytosine, thymine, and uracil) and form the basic structure of the barbiturates. [NIH] Quality of Health Care: The levels of excellence which characterize the health service or health care provided based on accepted standards of quality. [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] Quaternary: 1. Fourth in order. 2. Containing four elements or groups. [EU] Quiescent: Marked by a state of inactivity or repose. [EU] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from

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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] Radio Waves: That portion of the electromagnetic spectrum beyond the microwaves, with wavelengths as high as 30 KM. They are used in communications, including television. Short Wave or HF (high frequency), UHF (ultrahigh frequency) and VHF (very high frequency) waves are used in citizen's band communication. [NIH] Radioactive: Giving off radiation. [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] Radionuclide Imaging: Process whereby a radionuclide is injected or measured (through tissue) from an external source, and a display is obtained from any one of several rectilinear scanner or gamma camera systems. The image obtained from a moving detector is called a scan, while the image obtained from a stationary camera device is called a scintiphotograph. [NIH]

Radiopharmaceutical: Any medicinal product which, when ready for use, contains one or more radionuclides (radioactive isotopes) included for a medicinal purpose. [NIH] Radiotherapy: The use of ionizing radiation to treat malignant neoplasms and other benign conditions. The most common forms of ionizing radiation used as therapy are x-rays, gamma rays, and electrons. A special form of radiotherapy, targeted radiotherapy, links a cytotoxic radionuclide to a molecule that targets the tumor. When this molecule is an antibody or other immunologic molecule, the technique is called radioimmunotherapy. [NIH] Random Allocation: A process involving chance used in therapeutic trials or other research endeavor for allocating experimental subjects, human or animal, between treatment and control groups, or among treatment groups. It may also apply to experiments on inanimate objects. [NIH] Randomization: Also called random allocation. Is allocation of individuals to groups, e.g., for experimental and control regimens, by chance. Within the limits of chance variation, random allocation should make the control and experimental groups similar at the start of an investigation and ensure that personal judgment and prejudices of the investigator do not influence allocation. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Randomized clinical trial: A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be in a randomized trial. [NIH] Randomized Controlled Trials: Clinical trials that involve at least one test treatment and one control treatment, concurrent enrollment and follow-up of the test- and control-treated

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groups, and in which the treatments to be administered are selected by a random process, such as the use of a random-numbers table. Treatment allocations using coin flips, odd-even numbers, patient social security numbers, days of the week, medical record numbers, or other such pseudo- or quasi-random processes, are not truly randomized and trials employing any of these techniques for patient assignment are designated simply controlled clinical trials. [NIH] Reactivation: The restoration of activity to something that has been inactivated. [EU] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] 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] Reflex: An involuntary movement or exercise of function in a part, excited in response to a stimulus applied to the periphery and transmitted to the brain or spinal cord. [NIH] Reflux: The term used when liquid backs up into the esophagus from the stomach. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] 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] Relative risk: The ratio of the incidence rate of a disease among individuals exposed to a specific risk factor to the incidence rate among unexposed individuals; synonymous with risk ratio. Alternatively, the ratio of the cumulative incidence rate in the exposed to the cumulative incidence rate in the unexposed (cumulative incidence ratio). The term relative risk has also been used synonymously with odds ratio. This is because the odds ratio and relative risk approach each other if the disease is rare ( 5 percent of population) and the number of subjects is large. [NIH] Reliability: Used technically, in a statistical sense, of consistency of a test with itself, i. e. the extent to which we can assume that it will yield the same result if repeated a second time. [NIH]

Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Renal cell carcinoma: A type of kidney cancer. [NIH] Renal failure: Progressive renal insufficiency and uremia, due to irreversible and progressive renal glomerular tubular or interstitial disease. [NIH]

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Renal pelvis: The area at the center of the kidney. Urine collects here and is funneled into the ureter, the tube that connects the kidney to the bladder. [NIH] Renin: An enzyme which is secreted by the kidney and is formed from prorenin in plasma and kidney. The enzyme cleaves the Leu-Leu bond in angiotensinogen to generate angiotensin I. EC 3.4.23.15. (Formerly EC 3.4.99.19). [NIH] Renin-Angiotensin System: A system consisting of renin, angiotensin-converting enzyme, and angiotensin II. Renin, an enzyme produced in the kidney, acts on angiotensinogen, an alpha-2 globulin produced by the liver, forming angiotensin I. The converting enzyme contained in the lung acts on angiotensin I in the plasma converting it to angiotensin II, the most powerful directly pressor substance known. It causes contraction of the arteriolar smooth muscle and has other indirect actions mediated through the adrenal cortex. [NIH] Renovascular: Of or pertaining to the blood vessels of the kidneys. [EU] Reoperation: A repeat operation for the same condition in the same patient. It includes reoperation for reexamination, reoperation for disease progression or recurrence, or reoperation following operative failure. [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] 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] Resection: Removal of tissue or part or all of an organ by surgery. [NIH] Residual Volume: The volume of air remaining in the lungs at the end of a maximal expiration. Common abbreviation is RV. [NIH] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Response rate: The percentage of patients whose cancer shrinks or disappears after treatment. [NIH] Retinas: A membrane at the back of the eye which is sensitive to light stimuli and composed of the photoreceptors proper, i. e. the cones and rods, and the nerve cells which transmit to the optic nerve the stimulation of the receptor elements. [NIH] Retreatment: The therapy of the same disease in a patient, with the same agent or procedure repeated after initial treatment, or with an additional or alternate measure or follow-up. It does not include therapy which requires more than one administration of a therapeutic agent or regimen. Retreatment is often used with reference to a different modality when the original one was inadequate, harmful, or unsuccessful. [NIH]

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Retrograde: 1. Moving backward or against the usual direction of flow. 2. Degenerating, deteriorating, or catabolic. [EU] Retropubic: A potential space between the urinary bladder and the symphisis and body of the pubis. [NIH] 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] Retroviral vector: RNA from a virus that is used to insert genetic material into cells. [NIH] Ribonuclease: RNA-digesting enzyme. [NIH] Ribose: A pentose active in biological systems usually in its D-form. [NIH] Ribosome: A granule of protein and RNA, synthesized in the nucleolus and found in the cytoplasm of cells. Ribosomes are the main sites of protein synthesis. Messenger RNA attaches to them and there receives molecules of transfer RNA bearing amino acids. [NIH] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Risk patient: Patient who is at risk, because of his/her behaviour or because of the type of person he/she is. [EU] Rod: A reception for vision, located in the retina. [NIH] 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] Sarcoma: A connective tissue neoplasm formed by proliferation of mesodermal cells; it is usually highly malignant. [NIH] Sarcoplasmic Reticulum: A network of tubules and sacs in the cytoplasm of skeletal muscles that assist with muscle contraction and relaxation by releasing and storing calcium ions. [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] Screening: Checking for disease when there are no symptoms. [NIH] Scrotum: In males, the external sac that contains the testicles. [NIH]

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Sebaceous: Gland that secretes sebum. [NIH] Sebaceous gland: Gland that secretes sebum. [NIH] Seborrhea: Hypersecretion of sebum with excessive oily secretion from the sweat glands. [NIH]

Sebum: The oily substance secreted by sebaceous glands. It is composed of keratin, fat, and cellular debris. [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] Sediment: A precipitate, especially one that is formed spontaneously. [EU] Segregation: The separation in meiotic cell division of homologous chromosome pairs and 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] Self-Examination: The inspection of one's own body, usually for signs of disease (e.g., breast self-examination, testicular self-examination). [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] Seminal fluid: Fluid from the prostate and other sex glands that helps transport sperm out of the man's body during orgasm. Seminal fluid contains sugar as an energy source for sperm. [NIH] Seminal vesicles: Glands that help produce semen. [NIH] Seminiferous Epithelium: Specialized epithelium lining the seminiferous tubules containing developing and mature spermatozoa and Sertoli cells. [NIH] Seminiferous tubule: Tube used to transport sperm made in the testes. [NIH] Senescence: The bodily and mental state associated with advancing age. [NIH] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [NIH] Sensitization: 1. Administration of antigen to induce a primary immune response; priming; immunization. 2. Exposure to allergen that results in the development of hypersensitivity. 3. The coating of erythrocytes with antibody so that they are subject to lysis by complement in the presence of homologous antigen, the first stage of a complement fixation test. [EU] Sensor: A device designed to respond to physical stimuli such as temperature, light, magnetism or movement and transmit resulting impulses for interpretation, recording, movement, or operating control. [NIH] Septum: A dividing wall or partition; a general term for such a structure. The term is often used alone to refer to the septal area or to the septum pellucidum. [EU] 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

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synthesized from glycine or threonine. It is involved in the biosynthesis of purines, pyrimidines, and other amino acids. [NIH] Serologic: Analysis of a person's serum, especially specific immune or lytic serums. [NIH] Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (receptors, serotonin) explain the broad physiological actions and distribution of this biochemical mediator. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Serum Albumin: A major plasma protein that serves in maintaining the plasma colloidal osmotic pressure and transporting large organic anions. [NIH] Sex Characteristics: Those characteristics that distinguish one sex from the other. The primary sex characteristics are the ovaries and testes and their related hormones. Secondary sex characteristics are those which are masculine or feminine but not directly related to reproduction. [NIH] 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]

Sialic Acids: A group of naturally occurring N-and O-acyl derivatives of the deoxyamino sugar neuraminic acid. They are ubiquitously distributed in many tissues. [NIH] Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Silymarin: A mixture of flavonoids extracted from seeds of the milk thistle, Silybum marianum. It consists primarily of three isomers: silicristin, silidianin, and silybin, its major component. Silymarin displays antioxidant and membrane stabilizing activity. It protects various tissues and organs against chemical injury, and shows potential as an antihepatoxic agent. [NIH] Sitosterols: A family of sterols commonly found in plants and plant oils. Alpha-, beta-, and

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gamma-isomers have been characterized. [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]

Sneezing: Sudden, forceful, involuntary expulsion of air from the nose and mouth caused by irritation to the mucous membranes of the upper respiratory tract. [NIH] Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Social Security: Government sponsored social insurance programs. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Sodium Dodecyl Sulfate: An anionic surfactant, usually a mixture of sodium alkyl sulfates, mainly the lauryl; lowers surface tension of aqueous solutions; used as fat emulsifier, wetting agent, detergent in cosmetics, pharmaceuticals and toothpastes; also as research tool in protein biochemistry. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solitary Nucleus: Gray matter located in the dorsomedial part of the medulla oblongata associated with the solitary tract. The solitary nucleus receives inputs from most organ systems including the terminations of the facial, glossopharyngeal, and vagus nerves. It is a major coordinator of autonomic nervous system regulation of cardiovascular, respiratory, gustatory, gastrointestinal, and chemoreceptive aspects of homeostasis. The solitary nucleus is also notable for the large number of neurotransmitters which are found therein. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Somatic cells: All the body cells except the reproductive (germ) cells. [NIH] Somatomedins: Insulin-like polypeptides made by the liver and some fibroblasts and released into the blood when stimulated by somatotropin. They cause sulfate incorporation into collagen, RNA, and DNA synthesis, which are prerequisites to cell division and growth of the organism. [NIH] Sonogram: A computer picture of areas inside the body created by bouncing sound waves off organs and other tissues. Also called ultrasonogram or ultrasound. [NIH] Sound wave: An alteration of properties of an elastic medium, such as pressure, particle displacement, or density, that propagates through the medium, or a superposition of such alterations. [NIH] Spatial disorientation: Loss of orientation in space where person does not know which way

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is up. [NIH] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Sperm: The fecundating fluid of the male. [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] Sphincter: A ringlike band of muscle fibres that constricts a passage or closes a natural orifice; called also musculus sphincter. [EU] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spinal Nerves: The 31 paired peripheral nerves formed by the union of the dorsal and ventral spinal roots from each spinal cord segment. The spinal nerve plexuses and the spinal roots are also included. [NIH] Squamous: Scaly, or platelike. [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]

Standard therapy: A currently accepted and widely used treatment for a certain type of cancer, based on the results of past research. [NIH] Statistically significant: Describes a mathematical measure of difference between groups. The difference is said to be statistically significant if it is greater than what might be expected to happen by chance alone. [NIH] Steady state: Dynamic equilibrium. [EU] Steel: A tough, malleable, iron-based alloy containing up to, but no more than, two percent carbon and often other metals. It is used in medicine and dentistry in implants and instrumentation. [NIH]

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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] Stenosis: Narrowing or stricture of a duct or canal. [EU] Stent: A device placed in a body structure (such as a blood vessel or the gastrointestinal tract) to provide support and keep the structure open. [NIH] Sterile: Unable to produce children. [NIH] Sterility: 1. The inability to produce offspring, i.e., the inability to conceive (female s.) or to induce conception (male s.). 2. The state of being aseptic, or free from microorganisms. [EU] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] 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] Stress incontinence: An involuntary loss of urine that occurs at the same time that internal abdominal pressure is increased, such as with laughing, sneezing, coughing, or physical activity. [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] Stroma: The middle, thickest layer of tissue in the cornea. [NIH] Stromal: Large, veil-like cell in the bone marrow. [NIH] Stromal Cells: Connective tissue cells of an organ found in the loose connective tissue. These are most often associated with the uterine mucosa and the ovary as well as the hematopoietic system and elsewhere. [NIH] Struvite: A type of kidney stone caused by infection. [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] Submaxillary: Four to six lymph glands, located between the lower jaw and the submandibular salivary gland. [NIH]

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Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]

Sulfamoyl: AMPA/Kainate antagonist. [NIH] Sulfates: Inorganic salts of sulfuric acid. [NIH] Sulfuric acid: A strong acid that, when concentrated is extemely corrosive to the skin and mucous membranes. It is used in making fertilizers, dyes, electroplating, and industrial explosives. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Suppressive: Tending to suppress : effecting suppression; specifically : serving to suppress activity, function, symptoms. [EU] 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]

Surgical castration: Surgical removal of the testicles (orchiectomy) or ovaries (oophorectomy) to stop the production of sex hormones. Decreasing the levels of hormones may stop the growth of certain cancers. [NIH] Sweat: The fluid excreted by the sweat glands. It consists of water containing sodium chloride, phosphate, urea, ammonia, and other waste products. [NIH] Sweat Glands: Sweat-producing structures that are embedded in the dermis. Each gland consists of a single tube, a coiled body, and a superficial duct. [NIH] Sympathetic Nervous System: The thoracolumbar division of the autonomic nervous system. Sympathetic preganglionic fibers originate in neurons of the intermediolateral column of the spinal cord and project to the paravertebral and prevertebral ganglia, which in turn project to target organs. The sympathetic nervous system mediates the body's response to stressful situations, i.e., the fight or flight reactions. It often acts reciprocally to the parasympathetic system. [NIH] Sympathomimetic: 1. Mimicking the effects of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. 2. An agent that produces effects similar to those of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. Called also adrenergic. [EU] Symphysis: A secondary cartilaginous joint. [NIH] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Synapse: The region where the processes of two neurons come into close contiguity, and the nervous impulse passes from one to the other; the fibers of the two are intermeshed, but, according to the general view, there is no direct contiguity. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Synergistic: Acting together; enhancing the effect of another force or agent. [EU]

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Systemic: Affecting the entire body. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] 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] Testicles: The two egg-shaped glands found inside the scrotum. They produce sperm and male hormones. Also called testes. [NIH] Testicular: Pertaining to a testis. [EU] Testicular Hormones: Hormones produced in the testis. [NIH] Testis: Either of the paired male reproductive glands that produce the male germ cells and the male hormones. [NIH] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] Tetrodotoxin: Octahydro-12-(hydroxymethyl)-2-imino-5,9:7,10a-dimethano10aH(1,3)dioxocino(6,5-a)pyrimidine-4,7,10,11,12-pentol. An aminoperhydroquinazoline poison found mainly in the liver and ovaries of fishes in the order Tetradontiformes (pufferfish, globefish, toadfish), which are eaten. The toxin causes paresthesia and paralysis through interference with neuromuscular conduction. [NIH] Theca Cells: The connective tissue cells of the ovarian follicle. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thermal: Pertaining to or characterized by heat. [EU] Thermal ablation: A procedure using heat to remove tissue or a part of the body, or destroy its function. For example, to remove the lining of the uterus, a catheter is inserted through the cervix into the uterus, a balloon at the end of the catheter is inflated, and fluid inside the balloon is heated to destroy the lining of the uterus. [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] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]

Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] 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]

Dictionary 307

Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tissue Culture: Maintaining or growing of tissue, organ primordia, or the whole or part of an organ in vitro so as to preserve its architecture and/or function (Dorland, 28th ed). Tissue culture includes both organ culture and cell culture. [NIH] Tissue Expansion: Process whereby tissue adjacent to a soft tissue defect is expanded by means of a subcutaneously implanted reservoir. The procedure is used in reconstructive surgery for injuries caused by trauma, burns, or ablative surgery. [NIH] Tissue Harvesting: The removal of organs or tissue for reuse, for example, for transplantation. [NIH] Toilet Training: Conditioning to defecate and urinate in culturally acceptable places. [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] Tone: 1. The normal degree of vigour and tension; in muscle, the resistance to passive elongation or stretch; tonus. 2. A particular quality of sound or of voice. 3. To make permanent, or to change, the colour of silver stain by chemical treatment, usually with a heavy metal. [EU] Tonus: A state of slight tension usually present in muscles even when they are not undergoing active contraction. [NIH] Topical: On the surface of the body. [NIH] Torsion: A twisting or rotation of a bodily part or member on its axis. [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] Toxin: A poison; frequently used to refer specifically to a protein produced by some higher plants, certain animals, and pathogenic bacteria, which is highly toxic for other living organisms. Such substances are differentiated from the simple chemical poisons and the vegetable alkaloids by their high molecular weight and antigenicity. [EU] Trace element: Substance or element essential to plant or animal life, but present in extremely small amounts. [NIH] Tracer: A substance (such as a radioisotope) used in imaging procedures. [NIH] Traction: The act of pulling. [NIH] Transcriptase: An enzyme which catalyses the synthesis of a complementary mRNA molecule from a DNA template in the presence of a mixture of the four ribonucleotides (ATP, UTP, GTP and CTP). [NIH] Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. [NIH] Transduction: The transfer of genes from one cell to another by means of a viral (in the case

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of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transfer Factor: Factor derived from leukocyte lysates of immune donors which can transfer both local and systemic cellular immunity to nonimmune recipients. [NIH] Transferases: Transferases are enzymes transferring a group, for example, the methyl group or a glycosyl group, from one compound (generally regarded as donor) to another compound (generally regarded as acceptor). The classification is based on the scheme "donor:acceptor group transferase". (Enzyme Nomenclature, 1992) EC 2. [NIH] Transfusion: The infusion of components of blood or whole blood into the bloodstream. The blood may be donated from another person, or it may have been taken from the person earlier and stored until needed. [NIH] Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Translocation: The movement of material in solution inside the body of the plant. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Transrectal ultrasound: A procedure used to examine the prostate. An instrument is inserted into the rectum, and sound waves bounce off the prostate. These sound waves create echoes, which a computer uses to create a picture called a sonogram. [NIH] Transurethral: Performed through the urethra. [EU] Transurethral resection: Surgery performed with a special instrument inserted through the urethra. Also called TUR. [NIH] Transurethral Resection of Prostate: Resection of the prostate using a cystoscope passed through the urethra. [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] Treatment Outcome: Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, practicability, etc., of these interventions in individual cases or series. [NIH]

Triage: The sorting out and classification of patients or casualties to determine priority of need and proper place of treatment. [NIH] Tricyclic: Containing three fused rings or closed chains in the molecular structure. [EU] Trypsin: A serine endopeptidase that is formed from trypsinogen in the pancreas. It is converted into its active form by enteropeptidase in the small intestine. It catalyzes hydrolysis of the carboxyl group of either arginine or lysine. EC 3.4.21.4. [NIH]

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Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Tumor marker: A substance sometimes found in an increased amount in the blood, other body fluids, or tissues and which may mean that a certain type of cancer is in the body. Examples of tumor markers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and gastrointestinal tract cancers), and PSA (prostate cancer). Also called biomarker. [NIH] 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 suppressor gene: Genes in the body that can suppress or block the development of cancer. [NIH] Tumorigenic: Chemical, viral, radioactive or other agent that causes cancer; carcinogenic. [NIH]

Tumour: 1. Swelling, one of the cardinal signs of inflammations; morbid enlargement. 2. A new growth of tissue in which the multiplication of cells is uncontrolled and progressive; called also neoplasm. [EU] 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] 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] Urease: An enzyme that catalyzes the conversion of urea and water to carbon dioxide and ammonia. EC 3.5.1.5. [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] Ureteroscopy: Endoscopic examination, therapy or surgery of the ureter. [NIH] Ureters: Tubes that carry urine from the kidneys to the bladder. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]

Urethral Obstruction: Obstruction anywhere along the urethra. [NIH] Urethritis: Inflammation of the urethra. [EU] Urethrotomy: The operation of making an incision in the urethra. [NIH] Urinalysis: Examination of urine by chemical, physical, or microscopic means. Routine urinalysis usually includes performing chemical screening tests, determining specific gravity, observing any unusual color or odor, screening for bacteriuria, and examining the sediment microscopically. [NIH] Urinary: Having to do with urine or the organs of the body that produce and get rid of

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urine. [NIH] Urinary Calculi: Calculi in any part of the urinary tract. According to their composition or pattern of chemical composition distribution, urinary calculi types may include alternating or combination, cystine, decubitus, encysted, fibrin, hemp seed, matrix, mulberry, oxalate, struvite, urostealith, and xanthic calculi. [NIH] Urinary Fistula: An abnormal passage in any organ of the urinary tract or between urinary organs and other organs. [NIH] Urinary Retention: Inability to urinate. The etiology of this disorder includes obstructive, neurogenic, pharmacologic, and psychogenic causes. [NIH] Urinary tract: The organs of the body that produce and discharge urine. These include the kidneys, ureters, bladder, and urethra. [NIH] Urinary tract infection: An illness caused by harmful bacteria growing in the urinary tract. [NIH]

Urinary urgency: Inability to delay urination. [NIH] Urinate: To release urine from the bladder to the outside. [NIH] Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] Urodynamic: Measures of the bladder's ability to hold and release urine. [NIH] Urogenital: Pertaining to the urinary and genital apparatus; genitourinary. [EU] Urogenital Diseases: Diseases of the urogenital tract. [NIH] Urogenital System: All the organs involved in reproduction and the formation and release of urine. It includes the kidneys, ureters, bladder, urethra, and the organs of reproduction ovaries, uterus, fallopian tubes, vagina, and clitoris in women and the testes, seminal vesicles, prostate, seminal ducts, and penis in men. [NIH] Urologic Diseases: Diseases of the urinary tract in both male and female. It does not include the male genitalia for which urogenital diseases is used for general discussions of diseases of both the urinary tract and the genitalia. [NIH] Urologist: A doctor who specializes in diseases of the urinary organs in females and the urinary and sex organs in males. [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] 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 endothelial growth factor: VEGF. A substance made by cells that stimulates new blood vessel formation. [NIH] Vasectomy: An operation to cut or tie off the two tubes that carry sperm out of the testicles. [NIH]

Vasoconstriction: Narrowing of the blood vessels without anatomic change, for which constriction, pathologic is used. [NIH]

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Vasodilator: An agent that widens blood vessels. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venous: Of or pertaining to the veins. [EU] Venous Thrombosis: The formation or presence of a thrombus within a vein. [NIH] Venter: Belly. [NIH] Ventral: 1. Pertaining to the belly or to any venter. 2. Denoting a position more toward the belly surface than some other object of reference; same as anterior in human anatomy. [EU] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [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] Vesicoureteral: An abnormal condition in which urine backs up into the ureters, and occasionally into the kidneys, raising the risk of infection. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Virilism: Development of masculine traits in the female. [NIH] Virilization: The induction or development of male secondary sec characters, especially the induction of such changes in the female, including enlargement of the clitoris, growth of facial and body hair, development of a hairline typical of the male forehead, stimulation of secretion and proliferation of the sebaceous glands (often with acne), and deepening of the voice. Called also masculinization) [EU] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] Visceral Afferents: The sensory fibers innervating the viscera. [NIH] 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] Void: To urinate, empty the bladder. [NIH] Warts: Benign epidermal proliferations or tumors; some are viral in origin. [NIH] Watchful waiting: Closely monitoring a patient's condition but withholding treatment until symptoms appear or change. Also called observation. [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]

Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as

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may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) A substance-specific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU] Womb: A hollow, thick-walled, muscular organ in which the impregnated ovum is developed into a child. [NIH] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] 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] Zinc Fingers: Motifs in DNA- and RNA-binding proteins whose amino acids are folded into a single structural unit around a zinc atom. In the classic zinc finger, one zinc atom is bound to two cysteines and two histidines. In between the cysteines and histidines are 12 residues which form a DNA binding fingertip. By variations in the composition of the sequences in the fingertip and the number and spacing of tandem repeats of the motif, zinc fingers can form a large number of different sequence specific binding sites. [NIH] Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]

313

INDEX 5 5-alpha, 24, 66, 89, 91, 152, 153, 243, 265 A Abdomen, 243, 258, 278, 288, 304 Abdominal, 198, 243, 244, 287, 299, 304 Aberrant, 30, 71, 243 Ablation, 6, 23, 24, 33, 71, 103, 104, 112, 118, 119, 143, 194, 195, 223, 228, 243, 246 Acanthosis Nigricans, 184, 243 Acceptor, 243, 278, 287, 308 Acetylcholine, 243, 254, 284 Acne, 161, 184, 243, 258, 311 Acne Vulgaris, 161, 243 Acute renal, 186, 187, 191, 243 Acyl, 243, 301 Adaptability, 243, 253 Adaptation, 243, 290 Adenine, 243, 244, 295 Adenocarcinoma, 34, 44, 46, 78, 164, 172, 178, 179, 243, 294 Adenoma, 87, 155, 163, 168, 181, 193, 244 Adenosine, 90, 180, 244, 289 Adenosine Monophosphate, 180, 244 Adenosine Triphosphate, 90, 244, 289 Adenylate Cyclase, 180, 244 Adipocytes, 244, 257, 278 Adjuvant, 9, 52, 70, 108, 244 Adrenal Cortex, 170, 244, 264, 272, 292, 298 Adrenal Medulla, 152, 244, 252, 263, 285 Adrenaline, 244 Adrenergic Antagonists, 23, 244 Adrenoreceptor, 182, 183, 244 Adverse Effect, 4, 7, 12, 14, 19, 23, 24, 30, 244, 301 Afferent, 35, 56, 244, 278 Affinity, 36, 152, 163, 167, 173, 175, 244, 245, 248, 302 Age Groups, 21, 244 Aged, 80 and Over, 244 Ageing, 58, 131, 245 Agonist, 153, 154, 245, 261, 279 Algorithms, 63, 189, 245, 250 Alimentary, 245, 276, 277 Alkaline, 245, 246, 251, 287 Alkaloid, 245, 248, 283 Allergen, 245, 300 Allylestrenol, 181, 245

Alopecia, 161, 245 Alpha Particles, 245, 295 Alpha-1, 22, 81, 96, 100, 154, 167, 189, 245, 261, 292 Alternative medicine, 204, 245 Ameliorating, 180, 245 Amenorrhea, 245, 291 Amine, 245, 271 Amino Acid Sequence, 158, 176, 178, 179, 245, 247, 267 Amino Acids, 147, 245, 246, 254, 267, 288, 291, 294, 299, 301, 308, 309, 312 Aminopeptidases, 178, 245, 264 Ammonia, 245, 246, 269, 305, 309 Ampulla, 246, 263 Amputation, 25, 246 Anaesthesia, 246, 274 Anaesthetic, 87, 246 Anal, 246, 263, 265 Analog, 246, 259, 277, 278 Analogous, 246, 291, 308 Anaplasia, 246, 294 Anatomical, 10, 40, 69, 95, 246, 274 Androgen suppression, 12, 246 Androgenic, 161, 195, 246 Androgens, 28, 40, 44, 48, 49, 55, 58, 64, 71, 124, 134, 154, 160, 161, 183, 244, 246, 248, 272 Anesthesia, 8, 10, 11, 12, 17, 22, 53, 70, 157, 160, 193, 195, 198, 246 Anesthetics, 56, 246, 264 Angiotensinogen, 246, 298 Animal model, 34, 39, 70, 71, 246 Anionic, 246, 302 Anions, 246, 276, 301 Anoikis, 33, 246 Anomalies, 38, 186, 188, 191, 246, 283 Anovulation, 184, 246, 291 Antagonism, 155, 246 Antiandrogens, 161, 179, 247, 250 Antibacterial, 247, 303 Antibiotic, 247, 288, 303 Antibodies, 33, 43, 62, 158, 176, 179, 247, 270, 272, 273, 274, 282, 290 Anticoagulant, 247, 294 Antidiuretic, 247, 248, 259 Antidote, 247, 283 Antihypertensive, 156, 164, 168, 247

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Anti-inflammatory, 41, 181, 247, 268, 287 Antioxidant, 50, 247, 287, 301 Antiproliferative, 36, 247 Antiseptic, 247, 252 Antiviral, 247, 288 Anuria, 247, 277 Anus, 246, 247, 248, 255, 276, 289, 297 Apoptosis, 32, 33, 40, 41, 46, 63, 70, 71, 100, 113, 120, 246, 247, 252 Applicability, 173, 247 Approximate, 37, 248 Aqueous, 248, 249, 259, 278, 302 Arginine, 248, 259, 271, 290, 308 Argipressin, 248, 259 Aromatase, 153, 248 Arterial, 248, 268, 272, 294, 306 Arteries, 198, 248, 251, 257, 270, 283 Arteriolar, 248, 298 Arterioles, 248, 251, 281 Artery, 113, 248, 257, 262, 295, 298 Artificial Intelligence, 191, 248 Aseptic, 248, 286, 304 Assay, 33, 41, 49, 159, 248, 273 Astringent, 248, 252 Astrocytes, 248, 270 Astrocytoma, 248, 268 Asymptomatic, 56, 106, 175, 248 Atresia, 184, 248 Atrial, 248, 292 Atrophy, 28, 41, 248 Atropine, 248, 283 Autonomic Nervous System, 71, 249, 289, 302, 305 Axons, 249, 276, 292 B Bacteria, 243, 247, 249, 250, 262, 263, 281, 303, 307, 308, 310 Bactericidal, 249, 264 Bacteriuria, 249, 309 Balloon Dilatation, 3, 162, 191, 223, 249 Balloon dilation, 6, 17, 24, 26, 162, 202, 224, 249 Basal cells, 179, 249 Basal Ganglia, 249, 268 Base, 44, 65, 243, 249, 267, 277, 306 Basement Membrane, 249, 265 Benign tumor, 43, 76, 171, 249 Beta-Galactosidase, 92, 249, 277 Bicalutamide, 179, 250 Bilateral, 250, 291 Bile, 250, 266, 272, 278, 304 Biliary, 249, 250, 251

Biliary Tract, 250, 251 Binding Sites, 250, 312 Bioavailability, 173, 250 Biochemical, 11, 27, 40, 50, 54, 58, 76, 155, 163, 168, 250, 266, 277, 278, 301 Biofilms, 191, 250 Biological therapy, 250, 270 Biomarkers, 55, 56, 61, 62, 250 Biopsy, 10, 41, 48, 56, 61, 62, 73, 172, 187, 229, 250, 288 Biopsy specimen, 41, 250 Biosynthesis, 45, 250, 294, 301 Biotechnology, 78, 204, 215, 250 Biotransformation, 250 Bladder Calculi, 5, 108, 251 Blood pressure, 13, 20, 162, 163, 194, 240, 247, 251, 252, 268, 272, 273, 282, 285, 302 Blood transfusion, 198, 251 Blot, 251, 273 Blotting, Western, 251, 273 Body Fluids, 250, 251, 261, 302, 309 Body Mass Index, 90, 251 Bone Marrow, 175, 251, 267, 273, 279, 304 Bone metastases, 70, 251 Brachytherapy, 251, 275, 296 Breast Self-Examination, 251, 300 Bronchi, 251, 263, 277 Bronchial, 249, 251, 271 Bronchodilator, 251, 277 Bulbar, 27, 251 Bypass, 34, 251 C Calcium, 251, 256, 287, 299, 301 Calculi, 190, 249, 251, 310 Callus, 252, 286 Capsules, 29, 252, 261 Carbohydrates, 252, 253 Carcinogenesis, 101, 194, 252, 254 Carcinogenic, 252, 275, 286, 293, 304, 309 Cardiac, 160, 162, 169, 194, 198, 252, 259, 262, 263, 264, 283, 304 Cardiovascular, 16, 21, 85, 252, 301, 302 Cardiovascular disease, 85, 252 Cardiovascular System, 16, 252 Case series, 252, 254 Case-Control Studies, 37, 252, 263 Caspase, 33, 252 Castration, 8, 72, 154, 252 Cataract, 162, 252 Catechol, 45, 252 Catecholamine, 71, 252, 260, 289

315

Catheter, 12, 17, 21, 101, 156, 157, 159, 160, 249, 252, 276, 278, 306 Catheterization, 198, 249, 252, 276 Caudal, 252, 273, 291 Causal, 29, 253, 263, 299 Cause of Death, 165, 166, 253 Cell Adhesion, 253, 275 Cell Cycle, 36, 41, 76, 253, 258 Cell Death, 69, 74, 247, 253, 283 Cell Differentiation, 38, 74, 253, 301 Cell Division, 249, 253, 269, 280, 281, 282, 290, 300, 302 Cell Lineage, 69, 253 Cell membrane, 165, 166, 253, 259, 262, 289 Cell proliferation, 29, 34, 35, 41, 49, 58, 63, 64, 71, 74, 253, 286, 301 Cell Size, 165, 253, 266 Cell Survival, 41, 46, 253, 269 Central Nervous System, 7, 156, 163, 168, 180, 243, 249, 253, 267, 268, 269, 270, 301 Central Nervous System Infections, 253, 270 Ceramide, 33, 253, 277 Cerebral, 249, 253, 257, 263, 264, 268 Cerebral hemispheres, 249, 253, 268 Cerebrovascular, 252, 253 Cervix, 253, 298, 306 Chemopreventive, 33, 254 Chemotherapeutic agent, 161, 254 Chemotherapy, 170, 190, 254 Chlormadinone Acetate, 181, 254 Cholesterol, 162, 250, 254, 257, 261, 280, 304 Cholinergic, 49, 254, 287 Chondrocytes, 254, 265 Chromatin, 36, 247, 254, 279, 303 Chromosomal, 63, 254, 271 Chromosome, 68, 176, 254, 278, 300 Chronic renal, 5, 188, 254, 291 Chymotrypsin, 158, 254 Circumcision, 185, 189, 254 CIS, 49, 161, 220, 254 Clamp, 57, 228, 254 Clear cell carcinoma, 254, 259 Cleave, 178, 254 Clinical Medicine, 16, 22, 254, 292 Clinical series, 57, 254 Clinical study, 254, 257 Cloning, 68, 76, 250, 254 Coagulation, 10, 11, 193, 251, 255, 270, 278, 290, 306

Coculture, 125, 255 Coenzyme, 103, 255 Cofactor, 255, 285, 294, 306 Cohort Studies, 37, 255, 263 Collagen, 50, 54, 249, 255, 265, 293, 302 Colloidal, 255, 262, 301 Colon, 171, 255, 278 Colorectal, 33, 255 Combination Therapy, 91, 153, 154, 195, 255 Combinatorial, 60, 255 Comorbidity, 192, 255 Complement, 255, 256, 267, 275, 290, 300 Complementary and alternative medicine, 59, 129, 149, 256 Complementary medicine, 129, 256 Complete remission, 256, 297 Compliance, 22, 31, 36, 51, 54, 256 Computational Biology, 215, 256 Computer Simulation, 160, 256 Computer Systems, 248, 256 Conception, 256, 257, 265, 304 Concomitant, 71, 73, 256 Concretion, 251, 256 Conduction, 256, 306 Confusion, 256, 309 Congestion, 257, 259 Connective Tissue, 49, 251, 255, 257, 265, 267, 268, 279, 281, 299, 304, 306 Connective Tissue Cells, 257, 306 Constrict, 6, 257 Constriction, 182, 257, 276, 310 Consultation, 52, 186, 257 Contraceptive, 254, 257 Contractility, 75, 87, 101, 257 Contraindications, ii, 23, 198, 257 Control group, 24, 37, 257, 292, 296 Controlled clinical trial, 23, 32, 257, 297 Controlled study, 39, 90, 113, 257 Convulsions, 257, 283 Cooperative group, 32, 257 Cornea, 257, 304 Coronary, 113, 252, 257, 283 Coronary heart disease, 252, 257 Coronary Thrombosis, 257, 283 Corpus, 257, 279, 288, 292 Corpus Luteum, 257, 279, 292 Corrosion, 193, 199, 257 Cortex, 258, 264 Cranial, 258, 270, 289 Craniocerebral Trauma, 258, 270 Creatinine, 5, 26, 31, 202, 258, 277

316

Benign Prostatic Hyperplasia

Crossing-over, 258, 297 Cross-Sectional Studies, 258, 263 Cryptorchidism, 189, 191, 258 Curative, 258, 306 Cyclic, 169, 180, 244, 248, 258 Cyclin, 36, 38, 258 Cyproterone, 90, 258, 266 Cyproterone Acetate, 90, 258 Cyst, 251, 258 Cystectomy, 116, 258 Cystine, 258, 310 Cystitis, 116, 186, 187, 189, 190, 258, 287 Cystoscope, 198, 258, 308 Cystoscopy, 206, 228, 240, 258 Cytochrome, 248, 258 Cytokine, 56, 86, 259 Cytoplasm, 247, 253, 259, 269, 279, 299 Cytoskeleton, 259, 275 Cytotoxic, 191, 259, 296, 301 Cytotoxic chemotherapy, 191, 259 D Data Collection, 32, 52, 259 Decarboxylation, 259, 271 Decompensation, 5, 27, 50, 259 Decongestant, 156, 163, 168, 259, 283 Decubitus, 259, 310 Defense Mechanisms, 259, 275 Deletion, 247, 259, 267 Dendrites, 259, 284 Depolarization, 259, 301 Deprivation, 5, 26, 259 DES, 62, 178, 259 Desmopressin, 124, 259 Deuterium, 259, 272 Developmental Biology, 70, 76, 259 Diabetes Mellitus, 90, 197, 259, 268, 270 Diagnostic procedure, 151, 188, 204, 260 Diastolic, 260, 272 Diathermy, 198, 260, 281 Diffusion, 260, 275 Digestion, 245, 250, 260, 278, 304 Digital rectal examination, 6, 26, 223, 224, 225, 260 Dihydrotestosterone, 8, 11, 12, 40, 49, 66, 88, 174, 175, 243, 258, 260, 297 Dilation, 260 Dimerization, 60, 260 Direct, iii, 58, 59, 161, 169, 175, 207, 254, 260, 261, 291, 297, 305 Discrete, 62, 72, 260 Discrimination, 43, 78, 100, 114, 175, 260 Disease Progression, 30, 31, 61, 260, 298

Disease Susceptibility, 55, 260 Disinfectant, 260, 264 Dissection, 98, 191, 260, 279 Dissociation, 244, 260, 276 Distal, 29, 156, 165, 260, 262, 292, 294 Dizziness, 17, 20, 227, 260 Dopamine, 260, 284, 289 Dorsal, 40, 69, 72, 261, 291, 303 Dorsum, 261 Dosage Forms, 133, 261 Dosimetry, 195, 261 Double-blind, 11, 19, 20, 32, 52, 65, 79, 104, 129, 130, 132, 133, 135, 140, 261 Doxazosin, 20, 26, 33, 50, 79, 88, 89, 90, 91, 104, 109, 147, 175, 183, 194, 208, 228, 261 Drive, ii, vi, 4, 5, 23, 123, 186, 187, 190, 226, 227, 228, 229, 261, 278 Drug Interactions, 14, 21, 194, 208, 209, 261 Drug Tolerance, 261, 307 Duct, 74, 246, 252, 261, 264, 304, 305 Duodenum, 250, 254, 261, 263, 287, 304 Dysmenorrhea, 184, 261 Dyspnea, 259, 261 Dysuria, 10, 11, 192, 261 E Edema, 181, 259, 261, 284 Efficacy, 7, 8, 11, 13, 14, 20, 21, 23, 24, 26, 31, 32, 41, 52, 53, 59, 70, 89, 91, 95, 104, 105, 114, 115, 135, 142, 172, 174, 194, 195, 261, 308 Ejaculation, 4, 155, 194, 198, 202, 228, 261, 300 Elastin, 255, 261 Electrocoagulation, 255, 262 Electrode, 11, 262 Electrolyte, 160, 188, 262, 277, 281, 302 Electrons, 247, 249, 262, 276, 287, 295, 296 Electrophoresis, 99, 159, 262 Electroplating, 252, 262, 305 Electroporation, 165, 166, 262 Emboli, 113, 160, 262 Embolization, 113, 262 Embryo, 69, 253, 262, 274, 291 Embryology, 186, 190, 262 Endocrine System, 262, 284 Endocrinology, 76, 93, 94, 121, 154, 161, 170, 262 Endogenous, 49, 156, 164, 168, 244, 260, 262, 263, 307 Endometrial, 262 Endometriosis, 36, 262

317

Endometrium, 262, 280 Endorphins, 262, 285 Endoscope, 263 Endoscopic, 188, 195, 197, 258, 263, 309 Endothelial cell, 33, 263, 265, 271, 306 Endotoxin, 263, 309 End-stage renal, 254, 263, 291 Energy balance, 263, 278 Enkephalins, 263, 284 Enucleation, 79, 98, 263 Enuresis, 186, 187, 188, 189, 191, 263 Environmental Health, 125, 214, 216, 263 Enzymatic, 62, 158, 175, 251, 256, 263, 271, 280 Epidemiologic Studies, 58, 263 Epidermal, 46, 49, 110, 134, 263, 280, 311 Epidermal Growth Factor, 46, 110, 134, 263 Epidermal growth factor receptor, 110, 263 Epidermis, 249, 263, 295 Epinephrine, 152, 153, 244, 261, 263, 277, 284, 285, 309 Epithelium, 19, 29, 41, 45, 58, 63, 67, 72, 93, 116, 249, 264, 287, 293, 300 Equipment and Supplies, 15, 264 Erectile, 24, 42, 85, 162, 169, 188, 189, 190, 194, 198, 264, 288 Erection, 198, 264, 292 Erythrocytes, 251, 264, 300 Esophagus, 248, 264, 297, 304, 310 Estradiol, 72, 264 Estrogen, 8, 34, 36, 44, 48, 64, 121, 153, 174, 248, 258, 264, 279, 293 Estrogen receptor, 45, 48, 121, 264 Ethanol, 92, 179, 264 Ethnic Groups, 13, 42, 75, 264 Eukaryotic Cells, 264, 274 Evoke, 264, 304 Excitability, 56, 264 Excitation, 264, 266, 284 Excrete, 247, 264, 277 Exhaustion, 246, 264 Exocrine, 67, 264, 287 Exogenous, 250, 262, 264 Exopeptidases, 245, 264 Expiration, 265, 298 External-beam radiation, 265, 295 Extracellular, 33, 54, 180, 246, 248, 250, 257, 265, 275, 302 Extracellular Matrix, 33, 54, 246, 257, 265, 275

Extracellular Space, 265 Extracorporeal, 21, 190, 265 F Facial, 265, 302, 311 Fallopian tube, 265, 298, 310 Family Planning, 215, 265 Fat, 244, 251, 253, 257, 262, 265, 268, 278, 300, 302, 305 Fatigue, 20, 265, 270 Fetus, 161, 265, 290, 292, 310 Fibrin, 265, 306, 310 Fibroblast Growth Factor, 45, 84, 265 Fibroblasts, 54, 257, 265, 302 Fibrosis, 54, 189, 265 Fine-needle aspiration, 265, 283 Fistula, 25, 265 Fixation, 265, 300 Flatus, 266, 267 Flow Cytometry, 190, 266 Fluorescence, 266 Fluorescent Dyes, 266 Flutamide, 225, 266 Fold, 163, 167, 266, 292 Forearm, 251, 266 Fractionation, 62, 266 Free Radicals, 36, 247, 260, 266 Fungus, 266, 283 G Galactosides, 249, 266 Gallbladder, 243, 250, 266, 278 Gamma Rays, 267, 295, 296 Ganglia, 243, 267, 284, 289, 305 Ganglioside, 33, 267 Gas, 44, 246, 260, 266, 267, 272, 285 Gastric, 249, 261, 263, 267, 271 Gastrin, 267, 271 Gastrointestinal, 263, 264, 267, 301, 302, 304, 305, 309 Gastrointestinal tract, 264, 267, 301, 304, 309 Gene Deletion, 73, 267 Gene Expression, 27, 29, 36, 38, 55, 56, 69, 73, 74, 97, 98, 102, 171, 267 Gene Expression Profiling, 98, 267 Gene Therapy, 76, 267 General practitioner, 12, 267 Generator, 166, 195, 267 Genetic Code, 267, 285 Genetic Engineering, 250, 254, 267 Genetic Markers, 56, 267 Genetics, 46, 76, 268, 282 Genital, 185, 189, 220, 254, 268, 276, 310

318

Benign Prostatic Hyperplasia

Genitourinary, 18, 60, 69, 76, 186, 188, 190, 191, 268, 310 Genitourinary system, 186, 268 Genomics, 55, 73, 268 Genotype, 59, 72, 268, 289 Geriatric, 8, 24, 28, 137, 189, 205, 226, 268 Germ Cells, 268, 280, 287, 303, 306 Gestation, 58, 268, 288, 290 Glioblastoma, 71, 268 Glomerular, 268, 277, 297 Glomeruli, 268, 295 Glomerulonephritis, 187, 268 Glucocorticoids, 244, 268 Glucose, 259, 268, 270, 275, 299 Glucose Intolerance, 259, 268 Glucuronic Acid, 268, 270 Glutamic Acid, 147, 268, 269, 284, 293 Glutamine, 176, 269 Glycerol, 269, 289 Glycerophospholipids, 269, 289 Glycine, 148, 269, 284, 301 Glycoprotein, 71, 178, 269, 306, 309 Glycosidic, 269, 277 Gonadal, 269, 304 Gonadorelin, 269, 278 Gonadotropin, 8, 80, 269, 278 Gonads, 252, 269, 273 Governing Board, 269, 292 Gp120, 269, 288 Grade, 33, 72, 87, 110, 117, 170, 269, 294 Grading, 175, 269 Grafting, 269, 274 Granulocytes, 269, 278, 301, 311 Growth Disorders, 32, 269 Growth factors, 18, 19, 29, 37, 60, 63, 172, 173, 269, 275, 286 H Habitat, 270, 285 Haptens, 244, 270 Headache, 20, 270 Headache Disorders, 270 Health Status, 14, 42, 57, 66, 115, 196, 270 Heart attack, 252, 270 Heart failure, 270, 292 Heart Valves, 249, 270 Hematuria, 17, 46, 90, 94, 186, 188, 189, 220, 270 Hemodialysis, 270, 277 Hemoglobin, 264, 270, 276, 278 Hemoglobinopathies, 267, 270 Hemorrhage, 160, 198, 258, 262, 270, 304 Hemostasis, 198, 270, 275, 301

Heparan Sulfate Proteoglycan, 45, 270 Heparin, 45, 46, 270, 271 Heparin-binding, 45, 46, 271 Hepatic, 117, 271, 279 Heredity, 243, 267, 268, 271 Heterodimers, 271, 275 Heterogeneity, 97, 244, 271 Heterogenic, 271 Heterogenous, 45, 271 Hirsutism, 161, 184, 258, 271, 272, 273 Histamine, 163, 167, 271 Histidine, 271 Histology, 41, 73, 84, 271, 287 Histones, 36, 254, 271 Holmium, 10, 75, 79, 80, 98, 271 Homeobox, 58, 271 Homeostasis, 45, 271, 302 Homologous, 29, 40, 258, 267, 271, 275, 300, 305 Hormonal, 12, 24, 36, 37, 41, 45, 48, 64, 72, 108, 132, 161, 187, 195, 202, 248, 271 Hormonal therapy, 12, 187, 195, 271 Hormone therapy, 271 Human papillomavirus, 191, 271 Humoral, 62, 271 Humour, 271 Hybrid, 27, 74, 272 Hybridization, 72, 272, 282 Hybridomas, 262, 272 Hydrogen, 181, 243, 245, 249, 252, 259, 272, 278, 282, 285, 287, 294 Hydrolysis, 176, 249, 250, 272, 289, 291, 294, 308 Hydronephrosis, 26, 189, 272 Hydroxylysine, 255, 272 Hydroxyproline, 255, 272 Hydroxysteroid Dehydrogenases, 48, 49, 272 Hydroxysteroids, 272 Hyperandrogenism, 184, 272 Hyperlipidaemia, 169, 272 Hypersensitivity, 245, 272, 300 Hyperstimulation, 161, 272 Hypertension, 23, 99, 101, 104, 115, 156, 163, 168, 169, 190, 197, 252, 261, 270, 272, 289, 292 Hyperthermia, 4, 5, 12, 15, 36, 42, 99, 136, 138, 141, 143, 157, 191, 202, 240, 260, 272 Hypertrichosis, 271, 273 Hypogonadism, 42, 273 Hypospadias, 185, 273

319

Hypotension, 13, 17, 152, 153, 194, 257, 273 Hypotensive, 163, 273, 274 Hypothalamus, 249, 269, 273, 290 Hypothermia, 157, 273 Hypoxia, 50, 273 Hypoxic, 50, 273 I Imaging procedures, 273, 307 Immune response, 244, 247, 270, 273, 300, 305, 311 Immune Sera, 273 Immune system, 250, 273, 274, 310, 311 Immunity, 56, 273, 308 Immunization, 175, 273, 292, 300 Immunoassay, 158, 159, 175, 273 Immunoblotting, 44, 273 Immunogenic, 34, 273 Immunohistochemistry, 48, 63, 273 Immunologic, 273, 274, 296 Immunology, 190, 244, 266, 274 Impairment, 187, 274, 281 Implant radiation, 274, 275, 296 Implantation, 189, 193, 256, 274 Impotence, 4, 76, 106, 162, 185, 187, 188, 189, 191, 194, 198, 240, 264, 274, 288 In situ, 47, 48, 63, 274 In Situ Hybridization, 48, 63, 274 In vitro, 36, 48, 54, 59, 63, 65, 66, 68, 71, 72, 74, 88, 100, 176, 267, 274, 307 In vivo, 36, 54, 63, 64, 65, 68, 74, 100, 163, 267, 271, 274 Incidental, 88, 112, 274 Incision, 5, 6, 24, 26, 86, 107, 162, 198, 206, 223, 225, 226, 274, 276, 293, 299, 309 Indolent, 62, 175, 274 Indoramin, 183, 274 Induction, 33, 64, 246, 260, 274, 293, 311 Induration, 26, 274 Infant, Newborn, 244, 274 Infarction, 274, 298 Infection, 5, 14, 17, 27, 30, 31, 146, 155, 157, 160, 163, 168, 187, 188, 189, 190, 191, 197, 206, 248, 249, 250, 273, 274, 279, 288, 295, 304, 310, 311 Infertility, 34, 38, 74, 160, 184, 186, 188, 189, 190, 191, 275, 277 Infiltration, 86, 268, 275 Inflammation, 41, 71, 88, 172, 243, 247, 258, 265, 275, 290, 294, 295, 309 Informed Consent, 198, 275 Infusion, 275, 308

Initiation, 50, 55, 275, 307 Innervation, 155, 275 Inorganic, 167, 183, 275, 285, 305 Insight, 30, 38, 57, 61, 72, 73, 275 Insulin, 37, 63, 64, 83, 101, 114, 172, 173, 184, 275, 302 Insulin-dependent diabetes mellitus, 275 Insulin-like, 37, 63, 64, 101, 114, 172, 173, 275, 302 Insulin-Like Growth Factor Binding Protein 3, 37, 101, 275 Integrins, 33, 275 Intermittent, 181, 275 Internal Medicine, 27, 262, 275, 284 Internal radiation, 275, 296 Interneurons, 35, 275 Interstitial, 10, 53, 75, 86, 98, 102, 116, 124, 186, 189, 190, 193, 251, 265, 275, 276, 287, 297 Intestinal, 174, 276, 277 Intestines, 243, 248, 267, 276 Intoxication, 276, 312 Intracellular, 32, 45, 46, 164, 274, 275, 276, 280, 301 Intracellular Membranes, 276, 280 Intraepithelial, 171, 276 Intraocular, 162, 276 Intraocular pressure, 162, 276 Intrathecal, 57, 276 Intravenous, 228, 275, 276 Intravenous pyelogram, 228, 276 Intrinsic, 244, 249, 276 Intubation, 252, 276 Involuntary, 263, 276, 283, 297, 302, 304 Involution, 41, 276 Ionization, 62, 276 Ions, 249, 260, 262, 272, 276, 282, 299 Ischemia, 50, 248, 267, 276, 298 Isoflavones, 133, 276 Isoleucine, 158, 178, 276 Isoproterenol, 152, 277 K Kallikreins, 175, 277 Kb, 214, 277 Keratinocyte growth factor, 125, 277 Kidney Disease, 52, 214, 220, 221, 222, 228, 230, 272, 277 Kidney Failure, 187, 263, 277 Kidney Failure, Acute, 277 Kidney Failure, Chronic, 277 Kidney stone, 186, 187, 188, 272, 277, 284, 287, 304

320

Benign Prostatic Hyperplasia

Kidney Transplantation, 186, 277 Kilobase, 29, 277 Kinetic, 49, 277 L Labile, 173, 255, 277 Lactation, 277, 293 Lactosylceramides, 33, 277 Large Intestine, 276, 277, 297, 302 Laser Coagulation, 10, 86, 102, 193, 278 Laser Surgery, 6, 224, 225, 228, 278 Laser therapy, 103, 124, 206, 278 Lectin, 278, 280 Lens, 252, 278 Leptin, 83, 103, 278 Lesion, 27, 38, 160, 204, 278, 279 Leucocyte, 245, 278 Leukemia, 267, 278 Leuprolide, 125, 278 Libido, 4, 246, 278 Ligament, 265, 278, 293 Ligands, 36, 275, 278 Ligation, 56, 278 Linkage, 29, 268, 277, 278 Lipid, 165, 166, 269, 275, 278, 287 Lipid Peroxidation, 278, 287 Lithotripsy, 190, 278 Liver, 33, 173, 197, 243, 250, 266, 268, 270, 271, 278, 279, 281, 298, 302, 306, 309 Liver Cirrhosis, 197, 279 Lobe, 29, 40, 65, 72, 198, 279 Localization, 48, 84, 103, 164, 165, 273, 279 Localized, 34, 47, 50, 62, 68, 73, 175, 266, 271, 273, 274, 279, 290 Loop, 21, 68, 279 Lutein Cells, 279, 293 Luteinizing hormone-releasing hormone agonist, 124, 279 Lymph, 174, 175, 263, 271, 279, 304 Lymph node, 175, 279 Lymphadenectomy, 190, 279 Lymphatic, 274, 279, 281, 306 Lymphatic system, 279, 306 Lymphocytes, 37, 247, 268, 272, 273, 278, 279, 306, 311 Lymphocytic, 86, 279 Lymphoid, 247, 278, 279 Lysine, 271, 272, 279, 308 M Maintenance therapy, 13, 279 Malignancy, 45, 48, 73, 77, 188, 193, 243, 279, 287 Malignant tumor, 43, 45, 174, 279

Malnutrition, 248, 280, 283 Mammary, 48, 280 Manifest, 41, 57, 280 Man-made, 252, 280 Mediate, 27, 45, 46, 152, 153, 180, 261, 280 Mediator, 46, 68, 74, 280, 301 Medical castration, 8, 12, 280 Medical Records, 8, 14, 280 MEDLINE, 215, 280 Meiosis, 28, 280, 305 Melanin, 280, 289, 309 Melanocytes, 280 Melanoma, 33, 66, 174, 280 Melanosis, 243, 280 Membrane Lipids, 280, 289 Membrane Proteins, 152, 153, 280 Meninges, 253, 258, 280 Menopause, 189, 280, 291 Menstrual Cycle, 280, 293 Menstruation, 245, 261, 280, 281, 286 Mental, iv, 27, 214, 216, 256, 260, 265, 281, 292, 294, 295, 299, 300, 309 Mental Disorders, 281, 292 Mental Health, iv, 27, 214, 216, 281, 292, 295 Mercury, 266, 281 Mesenchymal, 58, 68, 72, 263, 281 Meta-Analysis, 31, 140, 144, 281 Metabolic disorder, 186, 281 Metaphase, 63, 281 Metastasis, 281 Metastatic, 65, 175, 184, 191, 281 Microcirculation, 279, 281 Microorganism, 255, 281, 311 Microwaves, 10, 11, 12, 159, 281, 296 Micturition, 35, 76, 108, 181, 281, 294 Milk Thistle, 281, 301 Mineralocorticoids, 244, 281 Mitochondrial Swelling, 282, 283 Mitosis, 28, 247, 282 Modeling, 132, 282 Modification, 58, 66, 173, 267, 282, 295 Modulator, 173, 282 Molecular mass, 158, 178, 282 Molecular Probes, 262, 282 Molecular Structure, 282, 308 Monitor, 22, 175, 224, 258, 282, 285 Monoclonal, 83, 159, 272, 273, 282, 296 Monoclonal antibodies, 83, 273, 282 Mononuclear, 282, 309 Monophosphate, 180, 282 Monotherapy, 23, 282

321

Morphogenesis, 29, 58, 282 Morphological, 35, 245, 262, 266, 280, 282 Morphology, 29, 65, 252, 282 Mucosa, 282, 293, 304 Multicenter Studies, 18, 283 Multicenter study, 22, 85, 104, 105, 283 Muscarine, 183, 283 Muscle Contraction, 152, 283, 299 Muscle Fibers, 283 Muscular Atrophy, 27, 283 Mutagenesis, 36, 283 Mutagenic, 44, 283 Mutagens, 283 Myocardial infarction, 104, 169, 257, 283 Myocardium, 283 N Naphazoline, 156, 163, 168, 283 Nausea, 261, 283, 309 NCI, 1, 66, 213, 220, 254, 283 Necrosis, 10, 12, 70, 166, 193, 195, 247, 268, 274, 283, 298 Needle biopsy, 157, 265, 283 Needs Assessment, 54, 283 Neonatal, 72, 283 Neoplasia, 72, 171, 284, 294 Neoplasm, 59, 161, 223, 284, 299, 309 Neoplastic Processes, 182, 284 Nephrolithiasis, 188, 284 Nephropathy, 74, 277, 284 Nephrosis, 284 Nephrotic, 187, 284 Nephrotic Syndrome, 187, 284 Nerve Endings, 152, 284 Nerve Growth Factor, 56, 284 Nervous System, 164, 168, 244, 249, 253, 280, 284, 289, 305 Networks, 39, 63, 159, 175, 284 Neural, 35, 56, 159, 175, 244, 271, 284 Neuroeffector Junction, 284 Neuroendocrine, 72, 81, 108, 284 Neurogenic, 116, 162, 189, 284, 310 Neurologic, 54, 268, 284 Neuromuscular, 46, 243, 284, 306 Neurons, 35, 57, 259, 267, 275, 284, 305 Neurotransmitter, 71, 76, 156, 164, 168, 243, 244, 260, 269, 271, 284, 285, 301, 305 Neutrons, 245, 285, 295 Niche, 51, 285 Nickel, 31, 83, 91, 99, 193, 202, 285 Nitrates, 108, 285 Nitric acid, 285

Nitrogen, 153, 169, 170, 245, 246, 266, 269, 277, 282, 285, 309 Nonmalignant, 182, 188, 285 Norepinephrine, 71, 152, 153, 156, 164, 168, 244, 261, 284, 285 Normotensive, 13, 20, 285 Nuclear, 34, 35, 40, 164, 165, 249, 262, 264, 267, 268, 280, 283, 285, 286, 294 Nuclei, 164, 165, 245, 262, 267, 271, 282, 285, 294 Nucleic acid, 178, 179, 267, 272, 274, 283, 285, 295 Nucleic Acid Hybridization, 272, 285 Nucleus, 247, 254, 258, 259, 263, 264, 267, 279, 280, 282, 285, 294, 302 O Observational study, 9, 285 Odds Ratio, 9, 37, 286, 297 Office Visits, 44, 286 Ointments, 261, 286, 287 Oligomenorrhea, 286, 291 Oliguria, 277, 286 Oncogenes, 191, 286 Oncogenic, 275, 286 Oncology, 113, 124, 134, 138, 188, 190, 191, 286 Oophorectomy, 286, 305 Opacity, 252, 286 Ophthalmic, 286, 291 Orchiectomy, 286, 305 Organ Culture, 71, 286, 307 Organogenesis, 29, 58, 286 Orgasm, 228, 261, 286, 300 Orthostatic, 13, 17, 286 Osmotic, 282, 286, 301 Osteoporosis, 28, 286 Outpatient, 12, 13, 17, 18, 22, 53, 157, 286 Ovarian Follicle, 257, 286, 306 Ovaries, 248, 272, 280, 286, 287, 291, 298, 301, 305, 306, 310 Ovary, 257, 264, 269, 286, 287, 291, 304 Overactive bladder, 56, 287 Ovulation, 246, 287 Ovum, 257, 268, 286, 287, 293, 312 Oxalate, 287, 310 Oxidation, 77, 243, 247, 250, 258, 278, 287 Oxidative Stress, 40, 287 Oxides, 162, 287 P Painful bladder syndrome, 188, 287 Palliative, 258, 287, 306 Pancreas, 243, 250, 254, 275, 287, 308, 309

322

Benign Prostatic Hyperplasia

Pancreatic, 254, 287 Pancreatic Juice, 254, 287 Papillomavirus, 287 Paraffin, 40, 287 Paralysis, 251, 287, 306 Parasympathomimetic, 283, 287 Paresthesia, 287, 306 Partial remission, 287, 297 Particle, 280, 288, 302, 308 Parturition, 288, 293 Patch, 57, 288 Pathologic, 15, 54, 116, 247, 250, 257, 272, 288, 291, 310 Pathologic Processes, 247, 288 Pathophysiology, 18, 23, 24, 31, 43, 49, 74, 115, 119, 190, 192, 197, 205, 288 Patient Compliance, 52, 288 Patient Education, 15, 23, 115, 202, 222, 229, 230, 234, 236, 242, 288 Patient Selection, 6, 12, 15, 22, 197, 288 Pelvic, 191, 262, 288, 293 Pelvis, 220, 243, 287, 288, 295, 310 Penicillin, 247, 288 Penile Prosthesis, 189, 288 Penis, 25, 190, 191, 261, 273, 288, 292, 298, 310 Peptide, 29, 44, 62, 63, 67, 175, 176, 264, 265, 278, 288, 291, 294 Peptide T, 67, 288 Percutaneous, 194, 278, 288 Perforation, 160, 198, 288 Perfusion, 273, 288 Perinatal, 186, 288 Perineal, 194, 205, 289, 296 Perineum, 273, 289 Perioperative, 10, 162, 289 Perioperative Care, 10, 289 Peripheral blood, 40, 289 Peripheral Nervous System, 164, 168, 263, 284, 289, 292, 305 Petroleum, 287, 289 Pharmaceutical Solutions, 261, 289 Pharmacokinetic, 289 Pharmacologic, 22, 33, 51, 57, 191, 246, 289, 307, 310 Pharmacotherapy, 16, 113, 134, 136, 138, 143, 289 Phenotype, 27, 38, 58, 59, 68, 71, 72, 267, 289 Phenoxybenzamine, 12, 156, 163, 168, 208, 289 Phenyl, 48, 162, 169, 289

Phenylalanine, 289, 309 Phospholipases, 289, 301 Phospholipids, 93, 265, 280, 289 Phosphorus, 251, 289 Phosphorylated, 255, 289 Phosphorylation, 58, 289 Photocoagulation, 255, 290 Physical Examination, 5, 6, 32, 189, 202, 225, 290 Physiologic, 46, 54, 57, 196, 245, 250, 280, 281, 290, 297 Physiology, 16, 22, 60, 76, 125, 187, 188, 190, 223, 225, 226, 227, 243, 262, 284, 290 Pigment, 280, 290 Pilot study, 40, 138, 290 Pituitary Gland, 265, 269, 290 Placenta, 248, 264, 290, 292 Plant Oils, 286, 290, 301 Plants, 18, 245, 248, 268, 278, 282, 285, 290, 291, 299, 301, 307 Plasma, 37, 62, 77, 95, 133, 175, 247, 253, 268, 270, 272, 277, 281, 290, 298, 300, 301 Plasma cells, 247, 290 Plasma Kallikrein, 277, 290 Plasma protein, 290, 301 Plasmids, 262, 290 Plasticity, 56, 290 Platelet Activation, 290, 301 Pneumonia, 257, 290 Pollen, 132, 148, 291 Polycystic, 161, 184, 187, 272, 291 Polycystic Ovary Syndrome, 161, 184, 272, 291 Polymers, 250, 291, 294 Polymorphism, 101, 125, 291 Polypeptide, 160, 245, 255, 263, 264, 272, 291, 293, 294, 312 Polysaccharide, 247, 291 Polyvinyl Alcohol, 113, 291 Posterior, 54, 246, 261, 287, 291 Postmenopausal, 286, 291 Postnatal, 67, 189, 291, 304 Postoperative, 10, 11, 16, 26, 193, 198, 227, 228, 291 Postoperative Complications, 10, 198, 291 Postoperative Period, 11, 26, 291 Postsynaptic, 284, 291, 301 Post-translational, 58, 173, 291 Postural, 194, 291 Potentiates, 65, 291 Potentiation, 291, 301 Practicability, 291, 308

323

Practice Guidelines, 81, 191, 202, 216, 291 Prazosin, 11, 12, 85, 120, 156, 163, 168, 181, 183, 208, 292 Precancerous, 254, 292 Preclinical, 75, 292 Precursor, 72, 246, 261, 262, 263, 285, 289, 292, 293, 309 Premalignant, 38, 204, 292, 293 Prenatal, 262, 292 Preoperative, 16, 118, 197, 227, 292 Prepuce, 254, 292 Presynaptic, 284, 292 Presynaptic Terminals, 284, 292 Prevalence, 20, 24, 42, 58, 73, 82, 86, 100, 102, 115, 120, 132, 161, 192, 196, 286, 292 Priapism, 187, 292 Primary endpoint, 37, 292 Primary Prevention, 37, 66, 292 Primary tumor, 44, 292 Primum, 106, 292 Probe, 5, 42, 47, 165, 292 Problem Solving, 248, 292 Progesterone, 36, 292, 293, 304 Prognostic factor, 191, 293 Progressive disease, 31, 57, 83, 293 Projection, 259, 276, 285, 293 Prolactin, 48, 77, 293 Proline, 255, 272, 293 Promoter, 29, 38, 39, 293 Prone, 186, 293 Prophylaxis, 153, 154, 293 Prospective Studies, 13, 293 Prospective study, 42, 107, 293 Prostate-Specific Antigen, 5, 26, 83, 85, 87, 92, 107, 157, 159, 187, 202, 220, 277, 293 Prostatic Intraepithelial Neoplasia, 164, 293 Prostatism, 23, 51, 154, 202, 223, 294 Prostatitis, 33, 146, 161, 180, 186, 187, 188, 221, 294 Prosthesis, 189, 294 Prosthesis Implantation, 189, 294 Protease, 43, 159, 176, 178, 255, 294 Protease Inhibitors, 43, 294 Protein C, 71, 116, 173, 245, 294, 309 Protein Conformation, 116, 245, 294 Protein Kinases, 286, 294 Protein S, 36, 62, 68, 250, 267, 294, 299 Proteinuria, 284, 294 Proteolytic, 245, 256, 277, 294 Protocol, 31, 32, 36, 40, 52, 53, 60, 294 Protons, 245, 272, 294, 295

Proximal, 23, 29, 165, 260, 292, 294 Psychic, 278, 281, 294, 300 Psychoactive, 294, 312 Psychogenic, 294, 310 Puberty, 38, 184, 295 Public Health, 25, 139, 216, 295 Public Policy, 215, 295 Publishing, 26, 78, 185, 186, 295 Pulmonary, 160, 251, 270, 277, 295, 305, 311 Pulmonary Artery, 251, 295, 311 Pulmonary Edema, 277, 295 Pulse, 165, 166, 282, 295 Purines, 295, 301 Pustular, 243, 295 Pyelonephritis, 187, 188, 295 Pyrimidines, 295, 301 Q Quality of Health Care, 295, 308 Quaternary, 294, 295 Quiescent, 29, 295 R Race, 55, 295 Radiation, 54, 187, 188, 190, 265, 266, 267, 273, 275, 280, 295, 296, 312 Radiation therapy, 54, 187, 188, 190, 265, 266, 275, 295 Radical prostatectomy, 48, 155, 189, 296 Radio Waves, 260, 281, 296 Radioactive, 272, 274, 275, 276, 280, 282, 285, 286, 296, 309 Radioisotope, 296, 307 Radiolabeled, 251, 296 Radiological, 220, 288, 296 Radionuclide Imaging, 188, 296 Radiopharmaceutical, 267, 296 Radiotherapy, 251, 296 Random Allocation, 296 Randomization, 52, 296 Randomized clinical trial, 8, 41, 53, 65, 66, 70, 112, 197, 296 Randomized Controlled Trials, 24, 296 Reactivation, 67, 297 Recombinant, 48, 49, 68, 176, 297, 311 Recombination, 68, 267, 268, 297 Rectal, 66, 157, 187, 206, 228, 240, 249, 297 Rectum, 22, 26, 174, 247, 255, 260, 266, 267, 274, 277, 293, 297, 308 Recurrence, 72, 156, 163, 168, 173, 187, 297, 298 Refer, 1, 189, 255, 260, 262, 265, 276, 279, 285, 297, 300, 307

324

Benign Prostatic Hyperplasia

Reflex, 35, 56, 297 Reflux, 190, 297 Refraction, 297, 303 Regeneration, 265, 297 Regimen, 179, 180, 261, 288, 289, 297, 298 Relative risk, 21, 297 Reliability, 81, 297 Remission, 30, 72, 279, 297 Renal cell carcinoma, 191, 297 Renal failure, 32, 297 Renal pelvis, 277, 298 Renin, 92, 246, 298 Renin-Angiotensin System, 92, 298 Renovascular, 188, 298 Reoperation, 189, 298 Reperfusion, 50, 298 Reperfusion Injury, 298 Reproductive system, 28, 34, 225, 293, 298 Research Design, 26, 298 Resection, 3, 4, 5, 6, 10, 11, 16, 17, 18, 24, 25, 51, 52, 53, 75, 79, 86, 96, 102, 103, 104, 105, 112, 116, 155, 157, 162, 193, 198, 205, 206, 223, 224, 225, 226, 241, 298, 308 Residual Volume, 32, 87, 298 Respiration, 282, 298 Response rate, 14, 298 Retinas, 249, 298 Retreatment, 17, 53, 298 Retrograde, 155, 194, 198, 202, 276, 299 Retropubic, 197, 205, 293, 296, 299 Retropubic prostatectomy, 296, 299 Retrospective, 13, 14, 66, 88, 106, 132, 299 Retrospective Studies, 13, 299 Retroviral vector, 267, 299 Ribonuclease, 49, 299 Ribose, 244, 299 Ribosome, 299, 308 Risk factor, 37, 44, 58, 66, 69, 84, 99, 187, 227, 228, 229, 263, 293, 297, 299 Risk patient, 7, 193, 198, 299 Rod, 254, 299 S Saponins, 299, 304 Sarcoma, 33, 299 Sarcoplasmic Reticulum, 49, 299 Schizoid, 299, 312 Schizophrenia, 299, 312 Schizotypal Personality Disorder, 299, 312 Screening, 5, 6, 10, 51, 61, 62, 63, 82, 118, 136, 172, 173, 175, 178, 189, 205, 220, 254, 299, 309

Scrotum, 241, 258, 299, 306 Sebaceous, 300, 311 Sebaceous gland, 300, 311 Seborrhea, 161, 300 Sebum, 243, 300 Secretion, 28, 43, 99, 154, 176, 183, 243, 263, 268, 269, 271, 272, 275, 277, 279, 281, 300, 311 Secretory, 67, 179, 284, 294, 300 Sediment, 300, 309 Segregation, 249, 297, 300 Seizures, 268, 300 Self-Examination, 186, 300 Semen, 6, 174, 176, 179, 225, 261, 293, 300 Seminal fluid, 172, 176, 300 Seminal vesicles, 172, 300, 310 Seminiferous Epithelium, 28, 300 Seminiferous tubule, 300, 303 Senescence, 84, 92, 300 Senile, 286, 300 Sensitization, 34, 300 Sensor, 43, 300 Septum, 292, 300 Sequence Homology, 288, 300 Serine, 158, 176, 178, 254, 277, 293, 300, 308 Serologic, 273, 301 Serotonin, 285, 289, 301, 309 Serum Albumin, 159, 301 Sex Characteristics, 76, 246, 295, 301, 306 Sexually Transmitted Diseases, 186, 188, 301 Shock, 190, 278, 301, 308 Sialic Acids, 33, 301 Signal Transduction, 69, 167, 182, 301 Signs and Symptoms, 16, 57, 187, 188, 189, 228, 297, 301 Silymarin, 173, 281, 301 Sitosterols, 131, 301 Skeletal, 246, 254, 269, 277, 299, 302 Skull, 258, 302, 306 Small intestine, 261, 271, 276, 302, 308 Sneezing, 302, 304 Social Environment, 295, 302 Social Security, 297, 302 Sodium, 57, 159, 281, 302, 305 Sodium Dodecyl Sulfate, 159, 302 Soft tissue, 251, 302, 307 Solitary Nucleus, 249, 302 Solvent, 264, 269, 286, 289, 302 Somatic, 271, 280, 282, 286, 289, 302, 306 Somatic cells, 280, 282, 302

325

Somatomedins, 275, 302 Sonogram, 302, 308 Sound wave, 256, 260, 302, 308 Spatial disorientation, 260, 302 Specialist, 189, 225, 231, 260, 303 Species, 29, 38, 69, 263, 266, 271, 272, 280, 282, 283, 290, 295, 300, 303, 305, 308, 312 Specificity, 43, 48, 108, 244, 303 Spectrum, 43, 74, 281, 296, 303 Sperm, 28, 174, 221, 225, 246, 254, 291, 300, 303, 306, 310 Spermatids, 28, 303 Spermatocytes, 28, 303 Spermatogenesis, 27, 303 Spermatogonia, 28, 303 Spermatozoa, 28, 176, 300, 303 Sphincter, 189, 303 Spinal cord, 35, 248, 253, 254, 276, 280, 284, 289, 292, 297, 303, 305 Spinal Nerves, 289, 303 Squamous, 46, 303 Staging, 175, 187, 189, 303 Standard therapy, 53, 303 Statistically significant, 9, 13, 19, 303 Steady state, 49, 303 Steel, 199, 254, 303 Stem Cells, 67, 72, 304 Stenosis, 186, 304 Stent, 193, 198, 304 Sterile, 12, 248, 304 Sterility, 275, 304 Steroid, 36, 37, 48, 72, 76, 154, 170, 245, 248, 299, 304 Stimulant, 271, 277, 304 Stimulus, 54, 257, 261, 262, 264, 275, 297, 304, 306 Stomach, 243, 264, 267, 271, 276, 283, 297, 302, 304 Stool, 255, 274, 278, 304 Stress, 10, 23, 41, 72, 162, 185, 187, 249, 252, 283, 287, 304 Stress incontinence, 162, 185, 187, 304 Stricture, 160, 188, 190, 304 Stroke, 214, 252, 304 Stroma, 45, 46, 67, 69, 93, 116, 177, 184, 304 Stromal, 14, 45, 46, 49, 59, 64, 68, 69, 70, 72, 73, 74, 101, 113, 125, 179, 182, 262, 304 Stromal Cells, 14, 49, 64, 69, 179, 304 Struvite, 304, 310 Subacute, 274, 304 Subarachnoid, 270, 304

Subclinical, 33, 274, 300, 304 Subcutaneous, 244, 261, 304 Submaxillary, 263, 304 Subspecies, 303, 305 Substance P, 300, 305 Sulfamoyl, 170, 305 Sulfates, 46, 302, 305 Sulfuric acid, 305 Suppression, 41, 246, 305 Suppressive, 124, 305 Surfactant, 302, 305 Surgical castration, 8, 305 Sweat, 300, 305 Sweat Glands, 300, 305 Sympathetic Nervous System, 71, 152, 153, 249, 305 Sympathomimetic, 244, 261, 263, 277, 285, 305 Symphysis, 293, 305 Synapse, 244, 284, 292, 305, 308 Synaptic, 152, 155, 163, 284, 301, 305 Synergistic, 77, 293, 305 Systemic, 191, 208, 251, 263, 274, 296, 306, 308 Systolic, 272, 306 T Telomerase, 134, 306 Temporal, 60, 72, 270, 306 Testicles, 189, 241, 246, 258, 280, 286, 299, 305, 306, 310 Testicular, 28, 154, 184, 186, 187, 189, 191, 197, 248, 258, 300, 306 Testicular Hormones, 28, 306 Testis, 8, 170, 264, 269, 306 Tetrodotoxin, 57, 306 Theca Cells, 184, 279, 306 Therapeutics, 132, 133, 171, 209, 306 Thermal, 8, 17, 21, 25, 52, 53, 70, 87, 156, 194, 202, 224, 225, 260, 285, 306 Thermal ablation, 87, 306 Threonine, 288, 301, 306 Threshold, 264, 272, 306 Thrombin, 265, 294, 306 Thrombomodulin, 294, 306 Thrombosis, 275, 294, 304, 306 Thymus, 273, 279, 306 Thyroid, 306, 309 Tissue, 6, 7, 11, 12, 17, 19, 21, 25, 28, 33, 39, 41, 42, 44, 46, 47, 48, 49, 54, 55, 56, 58, 59, 60, 61, 62, 63, 64, 67, 68, 70, 71, 72, 73, 86, 107, 108, 135, 143, 152, 153, 155, 156, 157, 159, 160, 163, 165, 166, 168,

326

Benign Prostatic Hyperplasia

170, 171, 172, 174, 176, 179, 189, 193, 195, 199, 228, 229, 244, 247, 248, 249, 250, 251, 255, 257, 258, 261, 262, 264, 265, 266, 269, 270, 271, 272, 273, 275, 276, 277, 278, 279, 280, 281, 283, 284, 286, 288, 290, 291, 293, 296, 297, 298, 301, 302, 304, 305, 306, 307, 308, 309, 312 Tissue Culture, 72, 307 Tissue Expansion, 46, 307 Tissue Harvesting, 61, 307 Toilet Training, 186, 307 Tolerance, 4, 15, 22, 74, 116, 243, 268, 307 Tone, 5, 23, 71, 155, 171, 177, 182, 285, 307 Tonus, 307 Topical, 8, 11, 22, 248, 264, 287, 307 Torsion, 187, 274, 307 Toxic, iv, 248, 273, 283, 285, 307 Toxicity, 261, 281, 307 Toxicokinetics, 307 Toxicology, 216, 307 Toxin, 113, 263, 306, 307 Trace element, 285, 307 Tracer, 35, 307 Traction, 254, 307 Transcriptase, 306, 307 Transcription Factors, 54, 60, 286, 307 Transduction, 69, 110, 180, 301, 307 Transfection, 63, 250, 262, 267, 308 Transfer Factor, 273, 308 Transferases, 45, 308 Transfusion, 11, 308 Translation, 76, 308 Translational, 61, 74, 308 Translocation, 43, 308 Transmitter, 156, 243, 248, 261, 280, 285, 308 Transplantation, 188, 190, 254, 273, 307, 308 Transrectal ultrasound, 87, 187, 308 Transurethral Resection of Prostate, 91, 293, 308 Trauma, 186, 188, 190, 283, 307, 308 Treatment Failure, 9, 18, 99, 308 Treatment Outcome, 15, 40, 53, 223, 308 Triage, 186, 308 Tricyclic, 181, 308 Trypsin, 254, 308, 312 Tryptophan, 255, 301, 309 Tumor marker, 39, 172, 173, 250, 309 Tumor Necrosis Factor, 110, 309 Tumor suppressor gene, 191, 309 Tumorigenic, 65, 309

Tumour, 172, 309 Tyrosine, 164, 167, 176, 261, 309 U Ultrasonography, 26, 119, 309 Unconscious, 246, 259, 309 Urea, 277, 305, 309 Urease, 285, 309 Uremia, 157, 277, 297, 309 Ureteroscopy, 103, 309 Ureters, 276, 277, 309, 310, 311 Urethra, 6, 12, 17, 23, 25, 46, 56, 155, 156, 157, 159, 160, 162, 163, 166, 168, 171, 174, 177, 181, 187, 206, 224, 227, 228, 249, 273, 288, 293, 294, 308, 309, 310 Urethral Obstruction, 87, 181, 182, 193, 309 Urethritis, 187, 189, 309 Urethrotomy, 198, 309 Urinalysis, 5, 26, 32, 202, 240, 309 Urinary Calculi, 188, 189, 310 Urinary Fistula, 188, 310 Urinary tract, 5, 6, 7, 8, 9, 14, 16, 18, 20, 23, 24, 26, 31, 32, 35, 36, 37, 44, 46, 50, 51, 53, 55, 56, 59, 75, 80, 81, 85, 86, 87, 88, 89, 90, 91, 98, 100, 101, 102, 105, 108, 114, 116, 124, 135, 137, 143, 154, 155, 157, 160, 162, 163, 166, 168, 175, 185, 186, 188, 189, 190, 191, 192, 194, 196, 197, 224, 229, 249, 310 Urinary urgency, 181, 240, 310 Urinate, 21, 174, 192, 206, 223, 225, 226, 227, 307, 310, 311 Urodynamic, 7, 10, 11, 14, 15, 18, 23, 25, 26, 53, 75, 79, 85, 95, 117, 188, 310 Urogenital, 29, 58, 60, 67, 72, 115, 188, 268, 310 Urogenital Diseases, 310 Urogenital System, 58, 60, 310 Urologic Diseases, 16, 186, 220, 221, 222, 228, 310 Urologist, 6, 7, 8, 186, 310 Uterus, 36, 253, 257, 262, 281, 287, 293, 298, 306, 310 V Vaccine, 244, 294, 310 Vagina, 253, 259, 281, 298, 310 Valves, 54, 249, 310 Varices, 249, 310 Vascular, 33, 46, 68, 88, 103, 113, 118, 270, 274, 277, 279, 281, 286, 290, 310 Vascular endothelial growth factor, 33, 118, 310

327

Vasectomy, 186, 189, 197, 310 Vasoconstriction, 263, 310 Vasodilator, 261, 271, 289, 311 Vector, 308, 311 Vein, 276, 285, 311 Venous, 198, 259, 294, 311 Venous Thrombosis, 198, 311 Venter, 311 Ventral, 40, 58, 69, 72, 273, 303, 311 Ventricle, 273, 295, 306, 311 Venules, 251, 281, 311 Vertebrae, 303, 311 Vesicoureteral, 190, 311 Veterinary Medicine, 215, 311 Viral, 286, 307, 309, 311 Virilism, 272, 311 Virilization, 184, 311 Virus, 253, 267, 269, 271, 299, 308, 311 Visceral, 249, 311

Visceral Afferents, 249, 311 Vitro, 36, 47, 59, 63, 271, 311 Vivo, 47, 54, 63, 64, 68, 311 Void, 30, 32, 53, 66, 75, 192, 311 W Warts, 271, 311 White blood cell, 247, 279, 290, 311 Withdrawal, 8, 24, 72, 74, 311 Womb, 298, 310, 312 Wound Healing, 265, 275, 312 X Xenograft, 246, 312 X-ray, 241, 266, 267, 276, 280, 285, 295, 296, 312 Y Yeasts, 266, 289, 312 Z Zinc Fingers, 60, 312 Zymogen, 172, 175, 176, 254, 294, 312

328

Benign Prostatic Hyperplasia

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